Abridging the CMOS Technology II.

As silicon CMOS devices approach their physical and technological miniaturization limits, Moore's Law is expected to persist for several more cycles, thanks to innovative, more compact layout structures [...].

Rapid management of Serratia marcescens outbreak in neonatology unit in Singapore: Risk factors and infection control measures.

BACKGROUND: We describe the investigations for control of two consecutive Serratia marcescens outbreaks in neonatology unit of Singapore General Hospital. METHODS: Epidemiological investigations, environmental sampling and risk-factors analysis were performed to guide infection control measures. Active surveillance sampling of nasopharyngeal aspirate and/or stool from neonates was conducted during both outbreaks. Whole-genome-sequencing was done to determine clonal links. Retrospective case-control study was conducted for second outbreak to identify risk factors for S marcescens acquisition. RESULTS: In 2022, two genetically unrelated S marcescens outbreaks were managed involving five neonates in March 2022 (outbreak 1) and eight neonates in November 2022 (outbreak 2). A link to positive isolates from sinks in intensive care units and milk preparation room was identified during outbreak 1. Neonatal jaundice (aOR, 16.46; p-value= 0.023) and non-formula milk feeding (aOR, 13.88; p-value= 0.02) were identified as risk factors during second outbreak. Multiple interventions adopted were cohorting of positive cases, carriage-screening, enhanced environmental cleaning, and emphasis on alcohol-based handrubs for hand-hygiene. CONCLUSION: The two outbreaks were likely due to infection prevention practices lapses and favourable environmental conditions. Nosocomial S marcescens outbreaks in neonatology units are difficult to control and require multidisciplinary approach with strict infection prevention measures to mitigate risk factors.

Contacts at the Nanoscale and for Nanomaterials.

Contact scaling is a major challenge in nano complementary metal-oxide-semiconductor (CMOS) technology, as the surface roughness, contact size, film thicknesses, and undoped substrate become more problematic as the technology shrinks to the nanometer range. These factors increase the contact resistance and the nonlinearity of the current-voltage characteristics, which could limit the benefits of the further downsizing of CMOS devices. This review discusses issues related to the contact size reduction of nano CMOS technology and the validity of the Schottky junction model at the nanoscale. The difficulties, such as the limited doping level and choices of metal for band alignment, Fermi-level pinning, and van der Waals gap, in achieving transparent ohmic contacts with emerging two-dimensional materials are also examined. Finally, various methods for improving ohmic contacts' characteristics, such as two-dimensional/metal van der Waals contacts and hybrid contacts, junction doping technology, phase and bandgap modification effects, buffer layers, are highlighted.

Comment on "Bipolar Resistive Switching in Lanthanum Titanium Oxide and an Increased On/Off Ratio Using an Oxygen-Deficient ZnO Interlayer".

The Mott-based resistive switching random access memory (RRAM) has been considered as a promising candidate for next-generation nonvolatile mass storage. Its performance relies on the oxygen migration process. In ACS Appl. Mater. Interfaces 2022, 14, 17682-17690, Wang et al. demonstrated that inserting a ZnO layer between the top tungsten electrode and the lanthanum titanium oxide (LTO) layer can improve the ON/OFF current ratio of the RRAM. This improvement was attributed to the increased oxygen vacancies in the ZnO layer. We argue their interpretation with the role, significance, and statistics of the oxygen vacancy in the samples. Our experimental evidence contradicts their claim, and we propose that hydroxy groups should be the responsible candidate for their claimed oxygen vacancy peak at around 531-532 eV in the O 1s photoelectron spectroscopy observed in their samples. We thus propose an alternative mechanism for the ON/OFF ratio enhancement with the ZnO interlayer: the ZnO layer prevents the LTO oxygen and hydroxy groups migration and from reacting with the multivalent tungsten electrode.

Predictors of disease severity in SARS-CoV-2 omicron variant XBB sublineages and variants of interest.

The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.

Reminder-dependent alterations in long-term declarative memory expression.

The reminder of a previously-learned memory can render that memory vulnerable to disruption or change in expression. Such memory alterations have been viewed as supportive of the framework of memory reconsolidation. However, alternative interpretations and inconsistencies in the replication of fundamental findings have raised questions particularly in the domain of human declarative memory. Here we present a series of related experiments, all of which involve the learning of a declarative memory, followed 1-2 days later by memory reminder. Post-reminder learning of interfering material did result in modulation of subsequent recall at test, but the precise manifestation of that interference effect differed across experiments. With post-reminder performance of a visuospatial task, a quantitative impairment in test recall performance was observed within a visual list-learning paradigm, but not in a foreign vocabulary learning paradigm. These results support the existence of reminder-induced memory processes that can lead to the alteration of subsequent memory performance by interfering tasks. However, it remains unclear whether these effects are reflective of modulation or impairment of the putative memory reconsolidation process.

Moist heat as a promising method to decontaminate N95 masks: A large scale clinical study comparing four decontamination modalities-moist heat, steam, ultraviolet-C irradiation, and hydrogen peroxide plasma.

BACKGROUND: Early in the COVID-19 pandemic, there was a global shortage of masks. Although mask reprocessing was practiced, no clinical study has assessed systematically the impact of repeated cycles of wear and decontamination on the integrity of N95 filtering facepiece respirators (FFRs). METHODS: We evaluated mask fit assessed by qualitative respirator fit test (QRFT) after each cycle of wear and decontamination, as well as four measures of mask integrity-bacterial filtration efficacy, particle filtration efficacy, differential pressure, and splash resistance through five cycles of wear and decontamination using one of the four modalities (moist heat, steam, ultraviolet-C irradiation, and hydrogen peroxide plasma). RESULTS: A total of 60.6% (hydrogen peroxide plasma) to 77.5% (moist heat) of the FFRs passed five cycles of wear and decontamination, as assessed by the wearers passing QRFT all five times. Moist heat-decontaminated FFRs retained all technical measures of integrity through all five cycles. CONCLUSIONS: This is the first large-scale study to assess systematically the impact (clinically and quantitatively) on N95 FFR integrity of repeated cycles of wearing followed by decontamination. Our results suggest that moist heat is a promising method for decontaminating N95 FFRs. Performing QRFT after every cycle of wear and decontamination ensures wearer safety. Although there is currently no mask shortage, reprocessing may reduce medical waste and improve sustainability.

Directed Versus Nondirected Standing Postures in Adolescent Idiopathic Scoliosis: Its Impact on Curve Magnitude, Alignment, and Clinical Decision-Making.

STUDY DESIGN: Prospective study. OBJECTIVE: To investigate the difference in major curve Cobb angle and alignment between directed and nondirected positioning for adolescent idiopathic scoliosis (AIS) and to evaluate implications on treatment decision-making. SUMMARY OF BACKGROUND DATA: Proper positioning of patients with spinal deformities is important for assessing usual functional posture in standing, so management strategies can be customized accordingly. Whether postural variability affects coronal and sagittal radiologic parameters and the impact of posture on management decisions remains unknown. PATIENTS AND METHODS: Patients with adolescent idiopathic scoliosis presenting for an initial consultation at a tertiary scoliosis clinic were recruited. They were asked to stand in two positions: passive, nondirected position; and directed position by the radiographer. Radiologic assessment included major and minor Cobb angle, coronal balance, spinopelvic parameters, sagittal balance, and alignment. Cobb angle difference >5° between directed and nondirected positioning was considered clinically impactful. Patients with or without such differences were compared. Overestimation or underestimation of the major curve (at 25° or 40°) by nondirected positioning were examined due to its relevance to bracing and surgical indications. RESULTS: This study included 198 patients, with 22.2% experiencing Cobb angle difference (>5°) between positioning. The major curve Cobb angle was smaller in nondirected than directed positioning (median difference: -6.0°, upper and lower quartile: -7.8, 5.8), especially for curves ≥30°. Patients with a Cobb angle difference had changes in shoulder balance ( P =0.007) when assuming a directed position. Nondirected positioning had 14.3% of major Cobb 25° underestimated and 8.8% overestimated, whereas 11.1% of curves >40° were underestimated. CONCLUSION: Strict adherence to a standardized radiographic protocol is mandatory for reproducing spine radiographs reliable for curve assessment, as a nondirected position demonstrates smaller Cobb angles. Postural variation may lead to overestimation, or underestimation, of the curve size which is relevant to both bracing and surgical decision-making. LEVEL OF EVIDENCE: Level-II.

Pharmacist-Managed Refill Service Impacts on Clinician Workload and Medication Interventions in a Federally Qualified Health Center.

INTRODUCTION: Increasing administrative workload is linked with lower quality of patient care and physician burnout. Conversely, models involving pharmacists can positively impact patient care and physician well-being. Research has consistently demonstrated that pharmacist-physician collaboration can improve outcomes for chronic diagnoses. Pharmacist-managed refill services may improve provider workload measures and clinical outcomes. METHODS: This was an evaluation of a pharmacist-managed refill service at a Federally Qualified Health Center (FQHC). Under collaborative practice agreement, pharmacists addressed refill requests and recommended interventions. Data analysis evaluated effectiveness of the model, including clinical interventions, and involved descriptive statistics and qualitative approaches. RESULTS: Average patient age was 55.5 years old and 53.1% were female. Turnaround time was within 48 h for 87.8% of refill encounters. During an average of 3.2 h per week, pharmacists addressed 9.2% (n = 1683 individual requests in 1255 indirect patient encounters) of the total clinic refill requests during the 1-year study period. In 453 of these encounters (36.1%), pharmacists recommended a total of 642 interventions. 64.8% of these were need for appointment (n = 211) or labs (n = 205). Drug therapy problems and medication list discrepancies were identified in 12.6% (n = 81) and 11.9% (n = 76) of encounters, respectively. DISCUSSION AND CONCLUSIONS: The results of this study are consistent with previous literature demonstrating the value of interprofessional collaboration. Pharmacists addressed refills in an efficient, clinically effective manner in an FQHC setting. This may positively impact primary care provider workload, patients' medication persistence, and clinical care.

Poole-Frenkel (PF)-MOS: A Proposal for the Ultimate Scale of an MOS Transistor.

This work reports, for the first time, the phenomenon of lateral Poole-Frenkel current conduction along the dielectric/Si interface of a silicon nanowire metal-oxide semiconductor (MOS) transistor. This discovery has a great impact on the study of device characteristic modeling and device reliability, leading to a new kind of electronic device with a distinct operation mechanism for replacing the existing MOS transistor structure. By measuring the current-voltage characteristics of silicon nanowire MOS transistors with different nanowire widths and at elevated temperatures up to 450 K, we found that the current level in the conventional ohmic region of MOS transistors, especially for the transistors with a nanowire width of 10 nm, was significantly enhanced and the characteristics are no longer linear or in an ohmic relationship. The enhancement strongly depended on the applied drain voltage and strictly followed the Poole-Frenkel emission characteristics. Based on this discovery, we proposed a new type of MOS device: a Poole-Frenkel emission MOS transistor, or PF-MOS. The PF-MOS uses the high defect state Si/dielectric interface layer as the conduction channel and is expected to possess several unique features that have never been reported. PF-MOS could be considered as the ultimate MOS structure from a technological point of view. In particular, it eliminates the requirement of a subnanometer gate dielectric equivalent oxide thickness (EOT) and eradicates the server mobility degradation issue in the sub-decananometer nanowires.

A Systematic Narrative Review of Implementation, Processes, and Outcomes of Human Library.

First started in Denmark in 2000, Human Library (HL) has been adopted by different communities around the world. It is an innovative approach that engages "readers" from the general public to have collaborative conversations with "books" from minority or marginalized communities to learn about their lived experiences and reduce public stigma and stereotypes. While the HL is popularized, its research base and implementation structure remain limited. This systematic narrative review aims to review the HL literature to (1) summarize the design, implementation, processes, and outcomes of existing HL programs and (2) synthesize recommendations for future implementation of more effective, ethical, and sensible HL. A systematic search in eight electronic databases yielded 23 journal articles and book chapters about HL published from 2010 to 2022. The identified literature demonstrated variations in format, venue, scale, preparation, and recruitment. A wide range of books with different social identities and from different cultural groups were reported, while readers were mostly from university and school communities. Reduced prejudices and improved attitudes were reported in readers, while both readers and books reported various facets of personal growth. Future HL using implementation guidelines with clearly articulate ethical considerations and diverse rigorous research methodologies are recommended.

Abridging CMOS Technology.

Whether from a device physics, fabrication technology, or process economics point of view, the practice of downsizing silicon-based CMOS devices will soon end [...].

Predictive factors for successful non-operative treatment and achieving MCID improvement in health-related quality of life in adult spinal deformity.

BACKGROUND: Adult spinal deformity is a spectrum of degenerative spinal diseases with increasing prevalence and healthcare burden worldwide. Identification of patients who are more likely to improve through conservative management may reduce cost and potentially prevent surgery and its associated costs and complications. This study aims to identify predictive factors for MCID in improvement of ODI and SRS-22r questionnaires in patients with adult spinal deformity treated with conservative treatment. METHODS: A prospective, observational cohort study of 46 patients was conducted at a spine specialist clinic. Inclusion criteria were 30-80 years of age, diagnosis of neglected adolescent idiopathic scoliosis, de-novo scoliosis, degenerative spondylolisthesis, and sagittal plane deformities (thoracic hypokyphosis, lumbar hypolordosis), presenting with mechanical back pain with or without radicular leg pain. All patients received conservative management including medication and physiotherapy. Radiological and clinical parameters were measured at baseline and at 1-year follow-up. Primary outcomes were ODI and SRS-22r scores. Secondary outcomes were EQ-5D-5L scores and requiring spine surgery during conservative treatment. Predictors for MCID improvement in ODI and SRS-22r were identified using multivariate regressions and receiver operating characteristic (ROC) analyses. RESULTS: At baseline, patients who reached MCID in ODI and/or SRS-22r showed less comorbidities (diabetes mellitus, hypertension, ischemic heart disease, osteoarthritis, cancer), smaller range of lateral spinal flexion, larger trunk shift, larger pelvic incidence, a higher EQ-5D-5L anxiety/depression dimension score, a lower SRS-22r total score, and presence of spondylolisthesis. Lateral flexion range < 25 degrees, trunk shift > 14 mm, pelvic incidence > 50 degrees, EQ-5D-5L anxiety/depression dimension score > 1, and SRS-22r total score < 3.5 were the cut-off values generated by ROC analysis. CONCLUSIONS: Both radiological and clinical predictive factors for MCID improvement in health-related quality of life were identified. Future research should identify subgroups of patients who are responsive to specific conservative treatment modalities, so as to provide information for personalized medicine. LEVEL OF EVIDENCE: II.

Novel L-RNA Aptamer Controls APP Gene Expression in Cells by Targeting RNA G-Quadruplex Structure.

Guanine quadruplex (G4) structure is a four-stranded nucleic acid secondary structure motif with unique chemical properties and important biological roles. Amyloid precursor protein (APP) is an Alzheimer's disease (AD)-related gene, and recently, we reported the formation of RNA G4 (rG4) at the 3'UTR of APP mRNA and demonstrated its repressive role in translation. Herein, we apply rG4-SELEX to develop a novel L-RNA aptamer, L-Apt.8f, which binds to APP 3'UTR D-rG4 strongly with subnanomolar affinity. We structurally characterize the aptamer and find that it contains a thermostable and parallel G4 motif, and mutagenesis analysis identifies the key nucleotides that are involved in the target recognition. We also reveal that the L-Apt.8f-APP D-rG4 interaction is enantiomeric-, magnesium ion-, and potassium ion-dependent. Notably, L-Apt.8f preferentially recognizes APP rG4 over other structural motifs, and it can control the APP reporter gene and native transcript translation in cells. Our work introduces a novel strategy and reports a new L-aptamer candidate to target APP 3'UTR rG4 structure, which laid the foundation for further applying L-RNA as an important class of biomolecule for practical L-aptamer-based targeting and controlling of gene expression in cells.

On the Vertically Stacked Gate-All-Around Nanosheet and Nanowire Transistor Scaling beyond the 5 nm Technology Node.

This work performs a detailed comparison of the channel width folding effectiveness of the FinFET, vertically stacked nanosheet transistor (VNSFET), and vertically stacked nanowire transistor (VNWFET) under the constraints of the same vertical (fin) height and layout footprint size (fin width) defined by the same lithography and dry etching capabilities of a foundry. The results show that the nanosheet structure has advantages only when the intersheet spacing or vertical sheet pitch is less than the sheet width. Additionally, for the nanowire transistors, the wire spacing should be less than 57% of the wire diameter in order to have a folding ratio better than a FinFET with the same total height and footprint. Considering the technological constraints for the gate oxide and metal gate thicknesses, the minimum intersheet/interwire spacing should be in the range of 7 to 8 nm. Then, the VNSFET structure has the advantage of boosting the chip density over the FinFET ones only when the sheet width is wider than 8 nm. On the other hand, the VNWFET structure may have a better footprint sizing than the FinFET ones only when the nanowire diameter is larger than 14 nm. In addition, considering the different channel mobilities along the different surface directions of the silicon channel and also some other unfavorable natures such as more complicated processes, more significant surface roughness scattering, and parasitic capacitance effects, the nanosheet transistor does not show superior scaling capability than the FinFET counterpart when approaching the ultimate technology node.

Alternative splicing modulation by G-quadruplexes.

Alternative splicing is central to metazoan gene regulation, but the regulatory mechanisms are incompletely understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold near splice junctions. The importance of G4s in RNA is emphasised by a higher enrichment for the non-template strand. RNA-seq data from mouse and human neurons reveals an enrichment of G4s at exons that were skipped following depolarisation induced by potassium chloride. We validate the formation of stable RNA G4s for three candidate splice sites by circular dichroism spectroscopy, UV-melting and fluorescence measurements. Moreover, we find that sQTLs are enriched at G4s, and a minigene experiment provides further support for their role in promoting exon inclusion. Analysis of >1,800 high-throughput experiments reveals multiple RNA binding proteins associated with G4s. Finally, exploration of G4 motifs across eleven species shows strong enrichment at splice sites in mammals and birds, suggesting an evolutionary conserved splice regulatory mechanism.

High-throughput characterization of the role of non-B DNA motifs on promoter function.

lternative DNA conformations, termed non-B DNA structures, can affect transcription, but the underlying mechanisms and their functional impact have not been systematically characterized. Here, we used computational genomic analyses coupled with massively parallel reporter assays (MPRAs) to show that certain non-B DNA structures have a substantial effect on gene expression. Genomic analyses found that non-B DNA structures at promoters harbor an excess of germline variants. Analysis of multiple MPRAs, including a promoter library specifically designed to perturb non-B DNA structures, functionally validated that Z-DNA can significantly affect promoter activity. We also observed that biophysical properties of non-B DNA motifs, such as the length of Z-DNA motifs and the orientation of G-quadruplex structures relative to transcriptional direction, have a significant effect on promoter activity. Combined, their higher mutation rate and functional effect on transcription implicate a subset of non-B DNA motifs as major drivers of human gene-expression-associated phenotypes.

Adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomized controlled trial.

AIM: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome. METHODS: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms. RESULTS: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo. CONCLUSION: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.