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Objective: The objective of this study was to assess caesarean section (CS) rates before and after the implementation of the Project Appropriate Birth (PPA), based on the Robson ten group classification system. Design: A before‐and‐after study. Setting: Maternity hospital in South Brazil. Population: All pregnant women attending from April 2016 to April 2017 (period 1, pre‐implementation of PPA) and from June 2017 to June 2018 (period 2, post‐implementation of PPA). Methods: Maternal and obstetric characteristics were evaluated, including Robson's classification, based on the characteristics of pregnancy and childbirth. A chi‐square test and crude and adjusted relative rates were used to analyse the study variables. The significance level was set at 5%. Main outcome measures: The CS rate for each group, their contribution to the overall CS rate and the differences in these contributions before and after PPA implementation. Results: The CS rates decreased from 62.4 to 55.6%, which represented a 10.9% reduction after the implementation of the PPA. Pregnant women in Robson classification groups 1–4 had a 21.4% reduction in CS rates, ranging from 49.1 to 38.6%. The greatest contributors to the overall CS rates were group 5 and group 2, accounting for more than 60% of the CS deliveries. Conclusion: The study results suggest that Project Appropriate Birth had an impact on the reduction of CS rates, especially in Robson classification groups 1 through 4, which indicates that providing mothers with evidence‐based interventions for labour and childbirth assistance contributed to reduce CS rates. The Project Appropriate Birth is an innovative project that has demonstrated promising results, suggesting that interventions based on scientific evidence can lead to real changes in childbirth care, contributing to reduce CS rates. The aim of the PPA is to promote activities to improve childbirth care and encourage vaginal delivery. In this study, 6238 pregnant women admitted to the hospital for delivery were included and classified into one of the Robson 10‐group classification. Findings revealed a 10.9% reduction in the overall CS rate and a 21.4% reduction for pregnant women in Robson classification groups 1 through 4, after the implementation of the PPA. The Project Appropriate Birth (PPA) is an innovative project that has demonstrated promising results, suggesting that interventions based on scientific evidence can lead to real changes in childbirth care, contributing to reduced caesarean section rates. The aim of the PPA is to promote activities to improve childbirth care and encourage vaginal delivery. In this study, 6238 pregnant women admitted to the hospital for delivery were included and classified using the Robson ten group classification system. Findings revealed a 10.9% reduction in the overall caesarean section rate and a 21.4% reduction for pregnant women in Robson classification groups 1–4, after the implementation of the PPA. Linked article This article is commented on by N Vrachnis, p. 81 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.16921. [ABSTRACT FROM AUTHOR]

Background: Qualitative studies could allow a more comprehensive understanding about the breadth of children's experiences and perspectives regarding the impact of dental caries treatment. Aim: To assess parental perception about children's oral health‐related quality of life (OHRQoL) following the rehabilitation of carious primary anterior teeth. Methods: A purposive sample of parents of preschool children attending a University Dental Clinic due to caries in primary anterior teeth was recruited. Qualitative individual interviews about parental perception regarding children's oral health were conducted, audio‐recorded, and transcribed verbatim. An interview guide was used, based on the instrument ECOHIS. The responses were analysed using a thematic analysis approach. Results: Mothers of 10 children aged 4‐8 years old participated. Four themes emerged during data analysis: (a) Perception about the presence and occurrence of caries; (b) Impact on the child's OHRQoL; (c) Impact on family's OHRQoL; and (d) Changes in OHRQoL following oral rehabilitation. Conclusion: Mothers of children with dental caries in anterior teeth reported impact on children's and family's life. Also, mothers' reports demonstrated that oral rehabilitation caused positive changes in their children's well‐being and everyday life. [ABSTRACT FROM AUTHOR]

This study presents a novel low‐pass continuous‐time filter based on the voltage flipped‐source‐follower (SF). The filter efficiently operates in CMOS 28 nm and improves the SF filters state‐of‐the‐art thanks to a dedicated circuit that operates in fully‐differential fashion (instead of the pseudo‐differential typically used in state‐of‐the‐art SF filters) with a dedicated Common‐Mode‐Feedback circuit. Thus this work extends the application of the SF filtering stages to the nm‐range technologies where threshold voltage (VTH) is only two times lower than the supply voltage (VDD) for what regards standard‐process MOS transistors. In order to validate the design concept, the proposed filter has been designed in CMOS 28 nm technology. Extensive simulation results of a 131 MHz −3 dB frequency proof‐of‐concept second‐order filter are proposed. The device consumes 510 µW power from a single 1 V supply‐voltage. In‐band integrated noise is 160 µVRMS and IIP3 is 19 dBm for 20 and 21 MHz input tones frequencies. Simulation results lead to 166 J−1 figure‐of‐merit, outperforming the analogue filter state‐of‐the‐art. [ABSTRACT FROM AUTHOR]

This paper presents a new mathematical approach to design an asynchronous pulse width modulation (APWM) for the switched mode power supply (SMPS). Unlike the conventional APWM that utilises a Hysteretic comparator based Asynchronous Pulse Width Modulation (HAPWM) to provide the self-oscillating property, the proposed APWM is based on a Binary comparator based Asynchronous Pulse Width Modulation (BAPWM) and a delay cell. This way, compared to the HAPWM, the mathematical analysis of the modulator is significantly simplified. This was achieved by replacing the describing function (DF) -based graphical method with a -linearised mathematical model. The introduced mathematical approach is extended to study the behaviour of the higher order self-oscillating modulators in terms of the harmonic distortion. To confirm the effectiveness of the analytical derivations, the BAPWMs are employed in a classic DC-DC buck converter and the system-level simulation results are provided. It is concluded that there is an acceptable degree of similarity between the simulation results and the deployed analytical calculations for different orders of the modulators. Finally, to validate these analytical and simulation results and also to compare the BAPWM performance with its HAPWM counterpart, both modulators are implemented using off-the-shelf components and their measurement results are presented. [ABSTRACT FROM AUTHOR]

Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot-Marie-Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene. [ABSTRACT FROM AUTHOR]

A 28 nm CMOS‐bulk lowpass analogue filter architecture is hereby proposed. The filter is based on an improved Active‐Gm‐RC structure, where both poles of a Miller‐compensated operational amplifier (OPAMP) have been used for synthesising a third‐order filter. Several well‐known issues related to the 28 nm process node have been hereby mitigated by proper circuit/design techniques, enabling large signal‐to‐noise ratio (SNR) and 13.5 dBm IIP3. The proposed circuital solution performs 59 dB‐SNR at 340 µW power consumption from a single 0.9 V supply‐voltage. This allows one of the higher figure‐of‐merit (156 dB) in sub‐1 V analogue filters state of the art. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to determine the frequency of mutations in tubulin genes ( TUBB2B, TUBA1A, and TUBB3) in patients with malformations of cortical development ( MCDs) of unknown origin. Method In total, 79 out of 156 patients (41 males, 38 females; age range 8mo-55y (mean age 13y 3mo, SD 11y 2mo) with a neuroradiological diagnosis of MCDs were enrolled in the study. The 77 excluded patients were excluded for the following reasons: suspected or proven diagnosis of pre- or perinatal ischaemic insult ( n=13); syndromic disease ( n=10); congenital infection ( n=14); pregnancy complicated by twin-to-twin transfusion syndrome ( n=2); proven mutations in known genes ( n=13); poor magnetic resonance imaging ( MRI) quality, or lack of informed consent ( n=25). A genetic analysis of the TUBA1A, TUBB2B and TUBB3 genes was carried out by direct sequencing of the coding regions of the relevant genes for each participant. Previously described patients with mutations in the TUBB2B and TUBA1A genes were reviewed; clinical and neuroradiological findings were compared and discussed. Results Two novel heterozygous mutations were detected: a heterozygous mutation in exon 4 of the TUBA1A gene (c.1160C>T) in a 5-year-old female with microcephaly, severe intellectual disability, and absence of language, and a c.1080 _1084del CCTGAins ACATCTTC in exon 4 of the TUBB2B gene in a 31-year-old female with microcephaly, spastic tetraparesis, severe intellectual disability, and scoliosis. Different types of cortical abnormalities, cerebellar vermis hypoplasia, and optic nerve hypoplasia/atrophy were detected on MRI. Dysmorphisms of the basal ganglia and the hippocampi with abnormalities of the midline commissural structures were present in both cases. Interpretation The consistent presence of hypoplastic and disorganized white matter tracts suggests that, in addition to defects in neuronal migration, disruption of axon growth and guidance is a peculiar feature of tubulin-related disorders. [ABSTRACT FROM AUTHOR]

A 4th‐order single‐loop follow‐the‐leader‐feedback (FLFB) low‐pass continuous‐time filter in CMOS 0.18 µm is hereby presented. The outstanding FLFB noise behaviour is exploited to allocate the power consumption to linearity performance. The low‐pass filter prototype features 22.5 MHz−3 dB frequency, 21.5 dBm‐IIP3 and 76 µVRMS input referred in‐band integrated noise. The overall power consumption is 7 mA from a 1.8 V supply voltage. The signal‐to‐noise ratio for a −40 dB‐total harmonic distortion is 69 dB. [ABSTRACT FROM AUTHOR]

Neurological disorders characterized by abnormal neuronal migration, organization, axon guidance, and maintenance have recently been associated with missense and splice-site mutations in the genes encoding [alpha]- and [beta]-tubulin isotypes TUBA1A, TUBB2B, TUBB3, and TUBA8. We found a novel heterozygous mutation c.419G > C in exon 4 of the gene encoding TUBB2B in a female with microcephaly, agenesis of the corpus callosum, open-lip schizencephaly of the left parietal lobe, extensive polymicrogyria, basal ganglia and thalami dysmorphisms, and vermis and right third nerve hypoplasia. The missense change results in a glycine to alanine substitution; the mutated residue falls within an invariant glycine-rich region and therefore is likely to result in impaired protein function and possibly microtubule formation. This study expands the spectrum of brain malformations associated with mutations in the [beta]-tubulin gene TUBB2B, supporting its critical role in migration/organization and axon guidance processes. In addition, it suggests a possible genetic aetiology of schizencephaly, thus strengthening the hypothesis that there is a common pathophysiological base in polymicrogyria and schizencephaly. [ABSTRACT FROM AUTHOR]

Neurological disorders characterized by abnormal neuronal migration, organization, axon guidance, and maintenance have recently been associated with missense and splice-site mutations in the genes encoding α- and β-tubulin isotypes TUBA1A, TUBB2B, TUBB3, and TUBA8. We found a novel heterozygous mutation c.419G > C in exon 4 of the gene encoding TUBB2B in a female with microcephaly, agenesis of the corpus callosum, open-lip schizencephaly of the left parietal lobe, extensive polymicrogyria, basal ganglia and thalami dysmorphisms, and vermis and right third nerve hypoplasia. The missense change results in a glycine to alanine substitution; the mutated residue falls within an invariant glycine-rich region and therefore is likely to result in impaired protein function and possibly microtubule formation. This study expands the spectrum of brain malformations associated with mutations in the β-tubulin gene TUBB2B, supporting its critical role in migration/organization and axon guidance processes. In addition, it suggests a possible genetic aetiology of schizencephaly, thus strengthening the hypothesis that there is a common pathophysiological base in polymicrogyria and schizencephaly. [ABSTRACT FROM AUTHOR]

A 4th-order single-loop follow-the-leader-feedback (FLFB) low-pass continuous-time filter in CMOS 0.18 μm is hereby presented. The outstanding FLFB noise behaviour is exploited to allocate the power consumption to linearity performance. The low-pass filter prototype features 22.5 MHz−3 dB frequency, 21.5 dBm-IIP3 and 76 μVRMS input referred in-band integrated noise. The overall power consumption is 7 mA from a 1.8 V supply voltage. The signal-to-noise ratio for a −40 dB-total harmonic distortion is 69 dB. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on compound heterozygosity in ALS2 gene in infantile-onset ascending spastic paralysis with bulbar involvement.

The progressive myoclonus epilepsies (PMEs) are a heterogeneous group of neurodegenerative disorders, typically presenting in late childhood. An etiologic diagnosis is achieved in about 80% of patients with PME, and genome‐wide molecular studies on remaining, well‐selected, undiagnosed cases can further dissect the underlying genetic heterogeneity. Through whole‐exome sequencing (WES), we identified pathogenic truncating variants in the IRF2BPL gene in two, unrelated patients presenting with PME. IRF2BPL belongs to the transcriptional regulators family and it is expressed in multiple human tissues, including the brain. Recently missense and nonsense mutations in IRF2BPL were found in patients presenting with developmental delay and epileptic encephalopathy, ataxia, and movement disorders, but none with clear PME. We identified 13 other patients in the literature with myoclonic seizures and IRF2BPL variants. There was no clear genotype–phenotype correlation. With the description of these cases, the IRF2BPL gene should be considered in the list of genes to be tested in the presence of PME, in addition to patients with neurodevelopmental or movement disorders. [ABSTRACT FROM AUTHOR]

Summary: In this work, we present the design of three different circuits for the measurement of resistive gas sensors. Schematic designs of each approach are discussed and simulated using HSPICE in a commercial CMOS 180 nm technology node. Their physical layout is also implemented. The three designs output a pulsed voltage signal whose period is modulated by the resistance of the sensor. They also implement differential measurement techniques in order to reduce the effect of temperature variations. The first design uses an operational amplifier and a resistor to measure the sensor and transduce its signal; the second one employs a Wheatstone bridge with common‐mode feedback and a bulk‐input OTA; and the third one utilizes a current‐mode Wheatstone bridge built with a current‐conveyor 2. The designs consume between 1.8 and 6.7μW; their temperature coefficient is always between 60 and 305 ppm/° C; and their resolution is between 0.25% and 1%. The circuits are compatible with sensors of a wide resistance range, being the best one tolerant to resistances between 2 M Ω and 1 G Ω. Therefore, these designs are ideal for low‐power autonomous applications in environments where temperature is not controlled. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks (MOF) and covalent organic frameworks (COFs) are promising nanocarriers for targeted drug delivery. Noncovalent interactions between frameworks and drugs play a fundamental role in the therapeutic uptake and release of the latter. However, the scope of framework functionalizations and deliverable drugs remains underexplored. Using a multilevel approach combining molecular docking and density functional theory, we show for a range of drugs and frameworks that experimentally reported release metrics are in good agreement with the in silico computed host–guest interaction energies. Functional groups within the framework significantly impact the strength of these host–guest interactions, while a given framework can serve as an efficient delivery agent for drugs beyond the prototypical few. Our findings identify the interaction energy as a reliable and relatively easy to compute descriptor of organic framework materials for drug delivery, able to facilitate their high‐throughput screening and targeted design towards extended‐release times. [ABSTRACT FROM AUTHOR]

Background: Pathogenic variants of ATP1A2 (OMIM ID: 182340) are usually associated with familial hemiplegic migraine type 2 (FHM‐2), alternating hemiplegia of childhood (AHC), early infantile epileptic encephalopathy (EIEE), transient cytotoxic edema, and so on. Here, we present a novel heterozygous ATP1A2 variant in a girl with alternating hemiplegia, febrile seizures, developmental delay (which subsequently subsided), and MELAS‐like syndrome (as indicated by brain MRI). The patient did not experience migraine with aura. Methods: The patient was an 8‐year‐old girl with normal growth and development. Beginning from the age of 3 years and 8 months, the patient experienced several episodes of alternating limb paralysis. The episodes were accompanied by the appearance of MELAS‐like findings on brain MRI, which corresponded to the hemiplegia. There were abnormal linear signals in the cerebral cortex on the opposite side of the hemiplegic limb. Each time the patient recovered from hemiplegia, and each time MRI showed no lesions remained after recovery. No obvious abnormality was found in other examinations. Finally, the patient underwent whole‐exome sequencing (WES). Results: WES revealed a novel and de novo heterozygous variant in the ATP1A2 (NM_000702.3) c.335C>A:p.Ala112Asp (not previously reported). We examined the variant position in the 3D protein structure and found that a missense mutation at this site is a nonconservative substitution. The variation is nonpolymorphic. It occurs at a very low frequency in the population, and its ACMG classification is likely pathogenic. Conclusion: At present, there are limited reports of mutations in the ATP1A2 gene causing AHC. This is the first case of brain MRI showing MELAS‐like imaging in an AHC patient, and more cases are needed for verification. Early genetic testing and family screening can aid in the diagnosis and treatment of genetic diseases. The relationship between ATP1A2 gene mutation genotype and clinical phenotype needs to be further studied. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is involved in neurological and physiological functions such as motor control. L‐3,4‐dihydroxyphenylalanine (L‐DOPA), a precursor of DA, is conventionally believed to be an inert amino acid precursor of DA, and its major therapeutic effects in Parkinson's disease (PD) are mediated through its conversion to DA. On the contrary, accumulating evidence suggests that L‐DOPA itself is a neurotransmitter. We here show that L‐DOPA potentiates DA D2 receptor (DRD2) signaling through GPR143, the gene product of X‐linked ocular albinism 1, a G‐protein‐coupled receptor for L‐DOPA. In Gpr143‐gene‐deficient (Gpr143−/y) mice, quinpirole, a DRD2/DRD3 agonist, ‐induced hypolocomotion was attenuated compared to wild‐type (WT) mice. Administration of non‐effective dose of L‐DOPA methyl ester augmented the quinpirole‐induced hypolocomotion in WT mice but not in Gpr143−/y mice. In cells co‐expressing GPR143 and DRD2, L‐DOPA enhanced the interaction between GPR143 and DRD2 and augmented quinpirole‐induced decrease in cAMP levels. This augmentation by L‐DOPA was not observed in cells co‐expressing GPR143 and DRD1 or DRD3. Chimeric analysis in which the domain of GPR143 was replaced with GPR37 revealed that GPR143 interacted with DRD2 at the fifth transmembrane domain. Intracerebroventricular administration of a peptide that disrupted the interaction mitigated quinpirole‐induced behavioral changes in WT mice but not in Gpr143−/y mice. These findings provide evidence that coupling between GPR143 and DRD2 is required for selective DRD2 modulation by L‐DOPA in the dorsal striatum. [ABSTRACT FROM AUTHOR]

This letter proposes an active‐passive cascaded bandpass filter based on the substrate‐integrated suspended line platform for the first time. By cascading an active‐RC highpass circuit with a passive‐LC lowpass filter circuit, the proposed filter achieves a GHz bandwidth, an extremely low cut‐off frequency, and a controllable in‐band gain. It has the advantages of compact size, DC‐offset cancellation, and self‐packaging. As proof of concept, a sixth‐order bandpass filter was designed and fabricated. The measured 3‐dB bandwidth is from 88 kHz to 1.1 GHz with a 5.8 dB in‐band gain, and the circuit area is only 0.021 × 0.022 λg, where λg is the guided wavelength at 0.55 GHz. [ABSTRACT FROM AUTHOR]

Objectives: Population isolates represent a focus of interest because of their particular genetic history and the possibility of mapping peculiar deleterious variants. Here we investigated the pattern of genetic variation in two North Italian villages: Rotzo (RTZ) and Stoccareddo (STC), in the Asiago plateau. Materials and methods: We genotyped over 800 individuals for more than 600.000 markers. We investigated the isolation level by analyzing runs of homozygosity (ROH) and the level of population structure. Then we estimated the time of admixture and the relationship between ancient genomes and these two villages. Finally, we looked at the effect of genetic drift on deleterious variants. Results: We highlighted a different isolation level between RTZ and STC; despite the average number of ROH being similar between the two villages, RTZ shows a higher level of total homozygosity. We estimated, from different sources, that the time of admixture for the ancestors of these two populations was between 113 and 88 generations ago. We discovered that a deleterious variant in MCUB gene (rs78025076), which is linked to several lipid traits, is entirely absent in RTZ and at 1%frequency in STC. In contrast, the risk allele frequency is 2% in Europe and 2.4% in North‐East Italy. Discussion: These results show the importance of a genetic characterization of geographically isolated populations. Their vast array of past history could highlight specific events in the past and help describe deleterious variants and traits distribution in different regions. [ABSTRACT FROM AUTHOR]

This paper presents a low power CMOS programmable gain amplifier (PGA) utilizing a novel gm‐boosting technique to increase the maximum achievable DC gain. The structure increases the effective transconductance of the circuit without any additional elements. The gain enhancement is accomplished without increasing the power consumption. The variable gain function is achieved by varying the effective transconductance of the circuit and its output resistance. The proposed PGA achieves a wide gain range of 47.5 dB from 2.1 to 49.6 dB with a constant bandwidth. According to the post‐layout simulation results of the proposed circuit in 0.18‐μm TSMC CMOS process the bandwidth and the input referred noise voltage at the maximum gain are 11.3 MHz and 10.76 nV/sqrt (Hz), respectively. The second and third harmonic distortions of the proposed PGA at the minimum gain are less than −72.4 and −40.7 dB, respectively. The core circuit of proposed PGA draws only 164 μA from a 1.2‐V supply voltage occupying an area of 29 μm * 26 μm. [ABSTRACT FROM AUTHOR]

Mutations in the human kinesin family member 5A (KIF5A) gene were recently identified as a genetic cause of amyotrophic lateral sclerosis (ALS). Several KIF5A ALS variants cause exon 27 skipping and are predicted to produce motor proteins with an altered C‐terminal tail (referred to as ΔExon27). However, the underlying pathogenic mechanism is still unknown. Here, we confirm the expression of KIF5A mutant proteins in patient iPSC‐derived motor neurons. We perform a comprehensive analysis of ΔExon27 at the single‐molecule, cellular, and organism levels. Our results show that ΔExon27 is prone to form cytoplasmic aggregates and is neurotoxic. The mutation relieves motor autoinhibition and increases motor self‐association, leading to drastically enhanced processivity on microtubules. Finally, ectopic expression of ΔExon27 in Drosophila melanogaster causes wing defects, motor impairment, paralysis, and premature death. Our results suggest gain‐of‐function as an underlying disease mechanism in KIF5A‐associated ALS. Synopsis: The ALS‐associated KIF5A ΔExon27 mutation drives the disease via a gain‐of‐function mechanism caused by constitutive activation and increased motor association and aggregation of mutant KIF5A. KIF5A ΔExon27 is aggregation‐prone and is neurotoxic.KIF5A ΔExon27 displays relieved autoinhibition, increased motor self‐association, and enhanced processivity on microtubules.ALS patient iPSC‐derived motor neurons express mutant KIF5A proteins.Ectopic expression of KIF5A ΔExon27 in Drosophila leads to abnormal wings, motor deficits, paralysis, and premature death. [ABSTRACT FROM AUTHOR]

Summary: Power consumption and image resolution are the major concerned while designing modern readout integrated circuits (ROICs) of Cadmium‐Telluride (CdTe)/Cadmium‐Zinc‐Telluride (CdZnTe) sensors for nuclear magnetic resonance imaging (MRI) and positron emission tomography (PET) applications. The key ROIC element, namely, preamplifier, must be monolithically integrated to the sensor chip and should guarantee low noise, low power, and high linearity along with assuring higher conversion gain and less chip area. A power immune, linear charge sensitive preamplifier (CSP) with a custom leakage current compensation feedback for (CdTe)/CdZnTe sensors is designed. A maximum power consumption of 120 μW, stable against process voltage and temperature (PVT) variations, is achieved. The compensation module cancels out current noise generated at the output of the circuit, lowering the power spectral density of about 84.26% than that of similar architectures, thus improving the signal‐to‐noise ratio (SNR) at the CSP output by a factor of 6.31. In turns, it injects about 100 pA of input direct‐current (DC) current and compensates the sensor leakage current therefore. Two input dynamics of (0.25–10) and (10.01–20)fC are achieved, providing two conversion factors of 23.06 and 19.00 mV/fC with 2.4% and 0.58% nonlinearity errors, respectively, using 1 pF sensor capacitance. Noise performance of the circuit is improved with 47.5 e‐rms and 62.46e−rms of equivalent noise charge (ENC) depending upon the input dynamic. The design is validated by Monte Carlo simulations and PVT analysis implemented in 65 nm complementary metal‐oxide semiconductor (CMOS) process, assuring a chip area of only 0.000246 mm2. [ABSTRACT FROM AUTHOR]

Research on fluxgate magnetic sensors (FMS) has been in progress for past decades and has become popular for high precision results, external magnetic field detection, and simple design structure. The basic fluxgate magnetic sensor structure consists of an excitation coil, and pickup coils twist around the soft magnetic material. Although sensor size is simple, researchers, and engineers have been looking for decades to take advantage and integrate these devices into the tiny circuitry. This review will discuss the classic and new‐related fluxgate sensor design structures. Moreover, this review presents the main existing of the conventional/ micro/PCB (Printed circuit board) devices, materials and elements used for the fabrication, analytical models, and simulation tools. Future challenges in the fluxgate sensor fabrication are analyzed critically, and alternative approaches for better design are presented. The review emphasizes the benefits of fluxgate sensors in terms of translation. The particular segment includes a comparison of micro technology design against printed circuit board design. Improvements in fluxgate sensor noise, sensitivity concerning design parameters are reviewed and summarized chronologically. Compared with the previous studies published several decades ago, it will help beginners learn the step‐by‐step fabrication stages of fluxgate sensors for advanced applications and also complete overview about fabrication advancements of fluxgate sensors. [ABSTRACT FROM AUTHOR]

The goal is to illustrate new errors about using the figures‐of‐merit NF and IIP, by investigating an AGC‐less microwatt ultrawideband gm‐boosted CMOS RF system with noise/distortion cancellation. The system composed of limiter and LNA is designed for 0.3–10.7 GHz at 1.8 V. Thanks to the limiter, the impact of noises and distortions is cancelled and the LNA acts linear without any saturation or block, as well as, it becomes AGC‐less. Additionally, achievements prove that NF and IIP sometimes can be accompanied by error, hence engineers must always consider all aspects of a system together during their evaluations. Although this work is not experimental, it applies different methods such as "Regenerating", "Comparing Calculations with Simulations" and "Monte Carlo" to demonstrate the reliability of achievements for applying in a SAW‐less RFIC. [ABSTRACT FROM AUTHOR]

Summary: In this paper, a design of reconfigurable frequency mixer is adapted with gallium nitride high‐electron‐mobility transistor (GaN HEMT) architecture under variable gain, different intermediate frequency (IF) bandwidth, and active/passive configuration for multidisciplinary applications supported by wireless local area network (WLAN) framework. The low band (LB) and high band (HB) are reconfigured by shunting the power between the switching and transconductance at the IF stage of the transistor. The transistor switching mode (active and passive) and logic levels are fixed at the input stage, and the input radio frequency (RF) signal is steering between the gate and drain terminals of transistors. The transistor gain is controlled by adjusting transconductance at the input RF stage and the current‐steering in transimpedance stage at the output. The simulation results show that the proposed circuit provides variable gain of 23/25 and 30/32 dB and noise figure of 14.5/12.5 at the LB and HB reconfigurable scenarios. Hence, it is suitable for transceiver optimistic functions with converge large bandwidth through shunting stages of reconfigurable frequency mixer and transconductance. [ABSTRACT FROM AUTHOR]

Electrochemistry of the silicon oxide dielectric layer, a notable insulator often used as a gate oxide, is counterintuitive, but addresses fundamental questions to yield novel scientific discoveries. In this minireview, the fundamental electron transfer mechanism of silicon oxide in the electrolyte solution is elucidated. The possible electrochemical reactions to date are discussed in detail, providing numerous potential areas of application which are elaborated and justified. This minireview not only provides background but also guides future research. [ABSTRACT FROM AUTHOR]

Electronic skins (e‐skins) have established themselves as a versatile technology to restore or enhance human perception, and potentially enable softer robotics. So far, the focus has been mostly on reproducing the traditional functions associated with human skin, such as, temperature, pressure, and chemical detection. New developments have also introduced nonstandard sensing capabilities like magnetic field detection, to spawn the field of magnetosensitive e‐skins. Adding a supplementary information channel—an electronic sixth sense—allows humans to utilize the surrounding magnetic fields as stimuli for touchless interactions. Due to their vectorial nature, these stimuli can be used to track motion and orientation in 3D, opening the door to various kinds of gestural control for interactive devices. This approach to tracking provides an alternative or complement to optic‐based systems, which usually rely on cameras or infrared emitters, that cannot easily capture fine motion when objects are far from the source or the line‐of‐sight is obtruded. Here, the background, fabrication techniques, and recent advances of this field are reviewed; covering important aspects like: directional perception, geomagnetic field detection, on‐site conditioning, and multimodal approaches. The aim is to give the reader a general perspective and highlight some new avenues of research, toward artificial magnetoception. [ABSTRACT FROM AUTHOR]

Textile electronics addresses fibers or fiber assemblies with electronic functions to generate, transmit, modulate, and detect electrons. Interactive textile electronic devices may provide suitable platforms for virtual reality (VR)/augmented reality (AR) applications because of their excellent performance and unique immersive features such as lightweight, handiness, flexibility, comfort, and low strain even under high deformations. This paper presents a systematic review of the literature on the state‐of‐the‐art of interactive devices, fabrication technologies, system integration, promising applications, and challenges involved in textile‐based VR/AR systems. [ABSTRACT FROM AUTHOR]

Purpose: In vivo range and dose verification based on proton‐induced acoustics (protoacoustics) is potentially a useful tool for proton therapy. Built upon our previous study with two‐dimensional reconstruction, the time reversal (TR) method was extended to three‐dimensional (3D) and evaluated at two treatment sites (head and liver) through simulation, with the emphasis on a number of aspects such as increased spatial coverage, computational workload, and signal interference among slices. Methods: Two mono‐energetic pencil beams were modeled in each site. The k‐Wave toolbox was used to investigate the propagation and TR reconstruction of acoustic waves. The performance was quantitatively assessed based on mean square error (MSE) for dose verification and Bragg peak localization error (ΔBP) for range verification, with regard to five parameters: number of sensors, sampling duration, sampling timestep, spill time, and noise level. Results: The respective impacts of five parameters are examined. Under the optimum setting, the achievable ΔBP can be limited within 1 voxel (voxel size: 3 × 3 × 3 mm3) and the achievable MSE can be limited below 0.02, for the head case (56 sensors) and the liver case (204 sensors), respectively. Conclusions: The feasibility of range and dose verification utilizing the 3D TR method is demonstrated, as the very first step. In spite of several challenges unique to the 3D case (spatial coverage, computational workload, and signal interference among slices, etc.), promising performance is found and can be further improved through optimizing the deployment of sensors. The proposed approach may find potential use in several applications: beam diagnostics, in vivo dosimetry, and treatment monitoring. [ABSTRACT FROM AUTHOR]

For example, MFSD12 might cotransport cysteine with a proton or other cation, making melanosomes more acidic and reducing pH-sensitive Tyrosinase activity; its loss might thus raise melanosome pH and make Tyrosinase more active. (a) Model of MFSD12-mediated cysteine import into (left) melanosomes or melanosome precursors and role in pheomelanin biosynthesis, and (right) lysosomes and subsequent cystine export by CTNS. For example, cysteine could be imported into the intermediate prior to division of melanosomes and late endosomes, accounting for some cysteine/cystine content during melanosome maturation (Figure 1b). [Extracted from the article]

In this review, we describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence synaptic vesicle cycling (SVC disorders). Pathogenic variants in each SVC disorder gene lead to disturbance of at least one SVC subprocess, namely vesicle trafficking (e.g. KIF1A and GDI1), clustering (e.g. TRIO, NRXN1 and SYN1), docking and priming (e.g. STXBP1), fusion (e.g. SYT1 and PRRT2) or re‐uptake (e.g. DNM1, AP1S2 and TBC1D24). We observe that SVC disorders share a common set of neurological symptoms (movement disorders, epilepsies), cognitive impairments (developmental delay, intellectual disabilities, cerebral visual impairment) and mental health difficulties (autism, ADHD, psychiatric symptoms). On the other hand, there is notable phenotypic variation between and within disorders, which may reflect selective disruption to SVC subprocesses, spatiotemporal and cell‐specific gene expression profiles, mutation‐specific effects, or modifying factors. Understanding the common cellular and systems mechanisms underlying neurodevelopmental phenotypes in SVC disorders, and the factors responsible for variation in clinical presentations and outcomes, may translate to personalized clinical management and improved quality of life for patients and families. [ABSTRACT FROM AUTHOR]

Feingold Syndrome type 1 (FS1) is an autosomal dominant disorder due to a loss of function mutations in the MYCN gene. FS1 is generally clinically characterized by mild learning disability, microcephaly, short palpebral fissures, short stature, brachymesophalangy, hypoplastic thumbs, as well as syndactyly of toes, variably associated with organ abnormalities, the most common being gastrointestinal atresia. In current literature, more than 120 FS1 patients have been described, but diagnostic criteria are not well agreed upon, likewise the genotype–phenotype correlations are not well understood. Here, we describe 11 FS1 patients, belonging to six distinct families, where we have identified three novel MYCN mutations along with three pathogenetic variants, the latter which have already been reported. Several patients presented a mild phenotype of the condition and they have been diagnosed as being affected only after segregation analyses of the MYCN mutation identified in the propositus. We also describe here the first ever FS1 patient with severe intellectual disability having a maternally inherited MYCN variant together with an additional GNAO1 mutation inherited paternally. Mutations in the GNAO1 gene are associated with a specific form of intellectual disability and epilepsy, thus the finding of two different rare diseases in the same patient could explain his severe phenotype. Therein, a thorough investigation is merited into the possibility that additional variants in patients with a MYCN mutation and severe phenotype do exist. Finally, in order to guarantee a more reliable diagnosis of FS1, we suggest using both major and minor clinical‐molecular diagnostic criteria. [ABSTRACT FROM AUTHOR]

Malformations of cortical development (MCDs) are a group of severe brain malformations associated with intellectual disability and refractory childhood epilepsy. Human missense heterozygous mutations in the 9 α‐tubulin and 10 β‐tubulin isoforms forming the heterodimers that assemble into microtubules (MTs) were found to cause MCDs. However, how a single mutated residue in a given tubulin isoform can perturb the entire microtubule population in a neuronal cell remains a crucial question. Here, we examined 85 MCD‐associated tubulin mutations occurring in TUBA1A, TUBB2, and TUBB3 and their location in a three‐dimensional (3D) microtubule cylinder. Mutations hitting residues exposed on the outer microtubule surface are likely to alter microtubule association with partners, while alteration of intradimer contacts may impair dimer stability and straightness. Other types of mutations are predicted to alter interdimer and lateral contacts, which are responsible for microtubule cohesion, rigidity, and dynamics. MCD‐associated tubulin mutations surprisingly fall into all categories, thus providing unexpected insights into how a single mutation may impair microtubule function and elicit dominant effects in neurons. [ABSTRACT FROM AUTHOR]

Summary: In this paper, two new complementary metal oxide semiconductor (CMOS) realizations for second‐generation voltage conveyor (VCII) are presented. The first proposed VCII has a very simple structure employing only six transistors. The second proposed VCII employs 11 transistors, and none of the transistors at both proposed circuits suffer from the body effect. Small‐signal analysis, parasitic elements, and input‐referred noise of the proposed VCIIs are given. Moreover, a new active element called voltage controlled second‐generation voltage conveyor (VC‐VCII) is proposed as dual element of current controlled second‐generation current conveyor (CCCII) active element. Its parasitic resistance at the Y terminal can be controlled electronically. Two presented CMOS structures of VCII are worked as VC‐VCII with slight modification. Proposed circuits are simulated in Cadence Analog environment using TSMC 0.18‐μm process parameters with ±0.9‐V supply voltages. Both CMOS structures occupy a small chip area of 276.8 and 271 μm2, respectively. The bandwidth of the current follower stage of the proposed VCIIs is found as 794 MHz, whereas the bandwidth of the voltage follower stage for the first and second proposed VCIIs is found as 2.57 and 1.92 GHz, respectively. As an application example, voltage‐mode first‐order low‐pass filter has been given with its tunable gain by using VC‐VCII. [ABSTRACT FROM AUTHOR]

A novel scheme for tunable complementary metal–oxide–semiconductor (CMOS) transconductor robust against process and temperature (PT) variations is presented. The proposed configuration is a voltage controlled circuit based on a double negative channel‐metal‐oxide‐semiconductor (NMOS) transistor differential pairs connected in parallel, which has low power and high linearity. The PT compensation is completed by two identical PT compensation bias voltage generators (PTCBVGs), which can guarantee the designed transconductor high tolerance for PT variations. A complete CMOS transconductor with PTCBVG has been designed and simulated using 0.18 μm technology. The effectiveness of PT compensation technique is proved. The simulation results of post‐layout are commensurate with pre‐layout. Post‐layout simulation results show that when temperature changes from − 40 to 85°C for different process corners (TT, SS, SF, FS and FF), the transconductance varies from 91.8 to 123.6 μS, the temperature coefficient is <1090 ppm/°C, the total harmonic distortion is from − 78 to −72dB at 1 MHz for 0.2 VPP input signal, −3 dB bandwidth changes from 2.5 to 5 GHz, input‐referred noise varies from 78.1 to 124.8 nV/sqartHz at 1 MHz and DC power is from 1.5 to 3.2 mW. [ABSTRACT FROM AUTHOR]

Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth. [ABSTRACT FROM AUTHOR]

The giant magneto‐impedance (GMI) effect has been, since its discovery, one of the most promising technologies in the development of magnetic sensors. Features such as high sensitivity, stability and low cost are the main reasons for the development of this type of magnetometers. This study reports the design, implementation and experimental characterisation of a high sensitivity GMI gradiometer, aimed at measuring low‐intensity magnetic fields. A first‐order gradiometer was designed, based on the impedance phase characteristics of two Co70Fe5Si15B10 amorphous ribbon‐shaped sensors connected to an electronic circuit that converts the magnetic field into an output voltage. The developed prototype can operate not only as gradiometer but also as two separate magnetometers, which allows it to incorporate a compensation system against deviations in the biasing field of the GMI sensors. The experimental results for the gradiometer showed a sensitivity of 99 mV/μT, a measuring range of ±30 μT, a magnetic noise of 5 nT Hz−1/2 at 5 Hz and a resolution of 40 nT within a 500 Hz bandwidth. The compensation system has shown a settling time of 1.6 s for perturbations in the range ±10 μT with a steady‐state error <0.02%. All experiments were performed in an unshielded environment. [ABSTRACT FROM AUTHOR]

Comparators are very important circuits that can be found in a variety of applications, especially comparators whose reference level can be controlled. In this paper, a voltage‐controlled comparator whose reference voltage is controlled by a control voltage and a programmable comparator whose reference voltage is controlled by an input bit pattern are presented. These two comparators are analyzed quantitatively. The performance of the two proposed comparators is verified by simulation using the Berkeley predictive‐technology models (BPTM) of the 45‐, 32‐, 22‐, and 16‐nm complementary metal‐oxide semiconductor (CMOS) technologies with power‐supply voltages, VDD, of 1, 0.9, 0.8, and 0.7 V, respectively. The proposed controlled comparator is compared with the conventional latch‐type comparator from the points of view of the response time, the output amplitude, and the power consumption. [ABSTRACT FROM AUTHOR]

The need for technologies based environmentally friendlier materials, able to minimize the global dependence on fossil fuel derivatives, promotes the development of new hybrid materials based on natural polymers, such as silk derivatives. This work reports on a new generation of magnetically active materials based on silk fibroin (SF) from Bombyx mori silkworm. Magnetic cobalt ferrite (CFO) nanoparticles are introduced in an SF polymer matrix to develop CFO/SF nanocomposites with filler contents of up to 20 wt%. It is shown that the inclusion of CFO nanoparticles affects the β‐sheet conformation of SF polymer having relevant effect on mechanical and thermal properties. The incorporation of conductive nanoparticles into nonconductive matrix, induces an increase in electric conductivity and also in dielectric constant. The primitive magnetic behavior of CFO nanoparticles is successfully maintained after their incorporation into SF, which has made possible the processing of magnetic SF. These results enable the design and fabrication of a fully functional magnetic actuator based on SF, proving the suitable natural polymer‐based magnetic materials for a new generation of environmental‐friendlier smart and multifunctional materials. [ABSTRACT FROM AUTHOR]

Summary: A 4th‐order Butterworth class‐AB current‐mode low‐pass filter is proposed, based on second‐generation Current Conveyors (CCII). Class‐AB operation allows high‐power efficiency and driving large loads with small quiescent currents. The CCII topology uses the class‐AB output buffer with error amplifiers: this topology is known to be sensitive to mismatch errors, which cause offsets in the error amplifiers, affecting the biasing current of the stage. This problem is solved via a control loop, which compensates the effect of mismatches. The technique is shown to be effective in Monte Carlo simulations with process variations and mismatches. Simulations have been carried out in 40 nm CMOS technology. The proposed filter achieves good power efficiency, thanks to the class‐AB architecture, and good dynamic range, thanks to the closed‐loop output buffer. A cut‐off frequency of 6 MHz, with 184 μW of total quiescent power consumption, is achieved, with a THD of ‐55 dB and a SNR of 49 dB. [ABSTRACT FROM AUTHOR]

Summary: A high‐order discrete‐time IIR low‐pass with complex poles using charge sampling is presented in a single‐stage structure by using a mathematical strategy. In comparison with the analog complex‐poles Gm‐C filters, the proposed filter consumes lower power and has good linearity, and all of the tunings are implemented only by capacitor sizes. The proposed filter is a seventh‐order Butterworth, but this method can be generalized to implement other complex pole filters like Tchebyshev and Elliptic. Post‐layout simulation results in 130‐nm complementary metal‐oxide‐semiconductor (CMOS) show an IIP3 of +18 dBm and a noise figure of 5 dB. The filter has a rejection of more than 110 dB in its stop band and consumes 1.5 mW with a 1.6‐V supply voltage, and circuit occupies an about 0.12 mm2 of silicon. [ABSTRACT FROM AUTHOR]