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Background: Pompe disease (PD) is an autosomal recessive lysosomal storage disorder caused by the deficient activity of acid alpha glucosidase (GAA) enzyme due to mutations in the GAA gene. As a result, undigested glycogen accumulates within lysosomes causing their dysfunction. From a clinical point of view, the disease can be classified in infantile-onset (IO) and late-onset (LO) forms. The common GAA c.-32-13T>G variant, found in 40–70% of LO-PD alleles, is a leaky splicing mutation interfering with the correct GAA exon 2 recognition by the spliceosome leading to the production of non-functional GAA transcripts. In this study, we used modified, GAA-tailored U1 snRNAs to correct the aberrant splicing determined by the c.-32-13T>G and other GAA exon 2-skipping mutations. Methods: A set of constructs expressing 5 different engineered U1 snRNAs was generated. A functional splicing assay using a GAA hybrid minigene carrying different variants known to affect GAA exon 2 splicing was used to test the effect of engineered U1 snRNAs on exon 2 inclusion. The effect on endogenously expressed GAA transcript and GAA enzymatic activity was assessed by transfecting patient-derived fibroblasts bearing the common c.-32-13T>G with the best performing modified U1 snRNA. Results: Modified U1-3, U1+1 and U1+6 snRNAs were all able to increase, in a dose-dependent manner, the inclusion of exon 2 within the transcript derived from the GAA minigene harbouring the c.-32-13T>G variant. The U1+1 was the most effective one (2,5 fold increase). Moreover, U1+1 snRNA partially rescued the correct splicing of GAA minigenes harbouring mutations that affect the 3’ss (c.-32-3C>G, c.-32-2A>G) and the 5’ss (c.546G>A, c.546G>C, c.546G>T). Notably, the treatment of patient-derived fibroblasts carrying the c.-32-13T>G mutation with the U1+1 snRNA increased the amount of normal GAA mRNA by 1,8 fold and the GAA enzymatic activity by 70%. Conclusions: we provide the proof-of-concept for the use of modified GAA-tailored U1 snRNAs, designed to potentiate the recognition of the GAA exon 2 5’ss, as therapeutic tools to correct the aberrant transcripts carrying variants that affect exon 2 splicing, including the common c.-32-13T>G variant. [ABSTRACT FROM AUTHOR]

Background: Rearing poultry under stressful high stocking density (HSD) conditions is a common commercial practice to increase profitability, despite its negative effects on broiler physiology and welfare. Many feed additives are used to alleviate the negative impact of such practices. This study investigated the ameliorative effects of guanidinoacetic acid (GAA) on growth performance, ingestive behavior, immune response, antioxidant status, stress indicators, and intestinal histomorphometry of broilers subjected to HSD. A total of 364 male broilers were randomly allocated into four treatments with 7 replicates each in a 2 × 2 factorial arrangement: two stocking densities (SD) (10 and 16 birds/m2) and two GAA levels (0 and 0.6 g/kg feed). Results: Body weight, weight gain, feed intake, feed conversion ratio, production efficiency factor, dressing yield, and ingestive behavior were negatively affected by HSD, whereas the mortality rate was unaffected (P > 0.05). GAA improved the overall growth performance and dressing percentage (P < 0.05). In the HSD group, the immune response decreased at d 21 (P < 0.05). Creatine kinase, glutathione peroxidase (GPX), superoxide dismutase, catalase, triglycerides, and villus length and width (ileum) were reduced, whereas corticosterone (CORT) was increased (P < 0.05). Moreover, GAA increased the hemagglutination-inhibition titer at 21 days and the levels of lactate dehydrogenase, GPX, and catalase and decreased the levels of creatinine, alanine aminotransferase, nitrite, triglycerides, and CORT (P < 0.05). SD and GAA did not affect malondialdehyde or other biochemical parameters (P > 0.05). Conclusions: Dietary GAA supplementation can improve productivity and antioxidant status and reduce stress in broilers reared in a HSD environment. [ABSTRACT FROM AUTHOR]

The aim of the current investigation was to examine the locomotor performance profile of elite ladies Gaelic football (LGF) players in relation to playing position and quarters of play. Thirty (n = 30) elite LGF players (age: 24 ± 4 years, height: 169 ± 5 cm, body mass: 61 ± 4 kg) were monitored using 10 Hz GPS technology (Playertek; Catapult Sports; Australia) resulting in 145 individual samples collected over 18 competitive matches across the 2021 and 2022 LGF seasons. Locomotor performance was determined across the following variables: total distance covered (TD, m), relative distance (m·min−1), high-speed running (HSR, ≥ 4.4 m·s−1), very high-speed running (VHSR, ≥ 5.5 m·s−1), relative HSR (RHSR; m·min−1), peak velocity (m·s−1), percentage peak velocity (%PeakV), accelerations (n; ≥ 3 m·s−2), and decelerations (n; ≤ −3 m·s−2). Data were classified based on playing position and quarter of play. The greatest TD was covered by half-backs, midfielders, and half-forwards, with these positions covering significantly greater distances than full-backs (p < 0.05). Similarly, half-backs, midfielders, and half-forwards covered the greatest high-speed distance (HSR). When running performance was analysed across quarters, a significant position by quarter interaction was observed for all running performance variables, except peak velocity and percentage peak velocity. A consistent trend for reduced locomotor performance was evident in the second and fourth quarters across all positional lines. The current data provide coaches with the position-specific locomotor requirements of LGF match-play, which can inform the design of training content for LGF players, along with match-day strategies. Given the reduction in locomotor performance observed across the match, performance staff may consider the use of nutritional interventions, rewarm-up strategies, or specific substitution policies to mitigate the decrement in locomotor performance observed across match-play. [ABSTRACT FROM AUTHOR]

In line with the fast progress of nanotechnology, it is important to have compact semiconductor devices to function and offer the best results at various technology nodes. Gate-All-Around (GAA) Nanowire Field Effect Transistor (FET) is one of the most promising structures. Nanowire having an 8 nm channel length with the same source and drain doping concentration is used for this analysis. This work uses the sp3d5s* tight-binding model for comparative analysis of Nanowire FET. The non-equilibrium Green's function (NEGF) approach is used for this simulation. The comparative analysis is made by changing the diameter of the nanowire, crystal orientation, and oxide thickness for different channel materials Si and GaAs. The results show that the GAA Si Nanowire is superior with a high current on-off (Ion/off) ratio of 1011 having a diameter of 1.5 nm. The nanowire with a small diameter shows the best result in terms of On-current (Ion) and Off-current (Ioff). For crystal orientation x[100] which is along the transport of carriers in nanowires, the results obtained are very good as compared to other orientations. The hydrostatic strain has been analyzed. The change in the current on-off ratio with hydrostatic strain makes them a leading option for future sensors. [ABSTRACT FROM AUTHOR]

The corrosion behaviour of mild steel (MS) has been investigated at, 25, 35 and 45 °C in different media containing either pure glacial acetic acid (AA) or mixed with different amounts of formic acid (FA). The results of weight loss (WL) experiments yielded the largest value of corrosion rate (CR) in pure glacial AA. The effect of addition of FA to GAA shows contrasting trends—the CR decreases while increasing FA content from 2 to 10%, whereas a slight increase in CR is observed when FA is varied from 10 to 20%. MS corrodes considerably faster in glacial acetic acid (GAA) at each studied temperature (T). It is inhibited by FA containing some water in it. This behaviour has been compared with that obtained earlier by electrochemical method. The decrease in CR may be attributed to the formation of a protective layer due to the presence of water in FA. The increase in T leads to an increase in CR. It is seen that the compositions of solutions and experimental T have a marked influence on the CR. The surfaces of the specimens prior to and after being subjected to corrosion have been analysed by visual inspection and Scanning Electron Microscopy (SEM). Conclusions drawn from the surface study support the results of WL experiments. [ABSTRACT FROM AUTHOR]

After more than five decades, Moore's Law for transistors is approaching the end of the international technology roadmap of semiconductors (ITRS). The fate of complementary metal oxide semiconductor (CMOS) architecture has become increasingly unknown. In this era, 3D transistors in the form of gate-all-around (GAA) transistors are being considered as an excellent solution to scaling down beyond the 5 nm technology node, which solves the difficulties of carrier transport in the channel region which are mainly rooted in short channel effects (SCEs). In parallel to Moore, during the last two decades, transistors with a fully depleted SOI (FDSOI) design have also been processed for low-power electronics. Among all the possible designs, there are also tunneling field-effect transistors (TFETs), which offer very low power consumption and decent electrical characteristics. This review article presents new transistor designs, along with the integration of electronics and photonics, simulation methods, and continuation of CMOS process technology to the 5 nm technology node and beyond. The content highlights the innovative methods, challenges, and difficulties in device processing and design, as well as how to apply suitable metrology techniques as a tool to find out the imperfections and lattice distortions, strain status, and composition in the device structures. [ABSTRACT FROM AUTHOR]

This article discusses the electrical properties of an Inverse Gaussian Junctionless Gate All Around (IG-JLT-GAA) field effect transistor for identifying neutral and charged bioanalytes. In this work, the inverse Gaussian doping profile enables the potent command of gate over charge in channel in the GAA structure, resulting in improved performance attributes such as OFF current, ON current, current ratio, subthreshold slope, drain-induced barrier lowering, threshold voltage, and transconductance for the proposed biosensor. The leakage current (OFF) is 10−17 A, and the drain current (ON) is 10−6 A, with their ratio of 10−11 fetched at K = 10. This article investigates the effect of varying dielectric constants of biomolecules immobilized in cavity reflects the enhancement in biosensor sensitivity due to the immobilization of high dielectric constant protein bioanalytes. The drain-induced barrier lowering (DIBL) and subthreshold swing (SS) are 4.4 mV/V and 60.6688 mV/dec, respectively, for K = 10. The estimated threshold voltage sensitivity (SVT) for various dielectric constant biomolecules was found to be 9.7 and 110.5 mV for K = 1 and K = 10, respectively. Further, the performance of the biosensor using well-known biotin biomolecules with K = 2.63 is studied, and the result shows that the biosensor performs outstandingly in all performance attributes required for the detection of charged and neutral biomolecules. [ABSTRACT FROM AUTHOR]

In this article, analysis of heating effect for a range of thermal resistance (Rth) and different ambient temperatures on the DC parameters of the proposed Silicon‐Gate All Around Dielectric Window Spaced‐Multi‐channel (Si‐GAA‐DWS‐multi‐channel) MOSFET is carried out. The performance of the device is examined through 3D‐ATLAS TCAD simulator, by performing the numerical and electrothermal analysis. Due to cylindrical dimension, the nanowire FETs undergoes undesirable self/lattice‐heating. The lattice heating of the device is calculated with respect to various device parameters such as channel length, drain‐source voltage, thermal resistance, ambient temperature, on‐current Ion, and off‐current Ioff. The proposed device parameter has been compared with the existing devices, mainly with Silicon‐Nanowire‐Dielectric Pocket Packed MOSFET (Si‐NW‐DPP FET) and Silicon‐Nanowire MOSFET (Si‐NW FET). The Si‐GAA‐DWS‐multi‐channel FET is found to be as the better device than the other two structures, as the leakage current of the device is improved by 1 and 2 decades, drain current increases by 1 and 1 decade, a minimum SS of 63.271 mV/dec and a minimum DIBL of 26.172 mV/V, respectively. The lesser the SS, the faster will be the device; hence the proposed structure can be considered as the finest prospect for VLSI/ULSI electronic chips. [ABSTRACT FROM AUTHOR]

In this article, we propose InxGa1−xAs gate-all-around (GAA) MOSFET where In0.53Ga0.47As is used as channel. These devices excel in their ability to precisely modulate the electric field across the channel region, offering unparalleled control over charge carrier flow, while simultaneously exhibiting remarkable immunity to short-channel effects. To further improve device performance, a novel multi-channel architecture has been introduced, featuring 12 intricately arranged and isolated channels. This innovative design has yielded significant improvements in the device’s on-current characteristics, enabling higher-speed and enhanced overall functionality. However, it’s imperative to address the thermal challenges associated with the choice of In0.53Ga0.47As as the channel material. The inherent properties of this compound introduce self-heating effects, which can adversely impact device reliability and efficiency, particularly under high-power operating conditions. Effectively mitigating these thermal concerns through advanced thermal management techniques and material optimization strategies, an unique heat sink is designed for self-heating reduction.

In this paper, a low-temperature SiO2 interfacial layer preparation using rapid thermal oxidation (RTO) process for gate-all-around (GAA) nanosheet (NS) based input-output (I/O) transistor is explored in detail. After preparing high-quality thick SiO2 IL at 600℃, its MOS capacitor with W/TiN/HfO2/SiO2/Si substrate structure achieves well behaved multi-frequency capacitance-voltage characteristics, low leakage current, low interfacial trap density (Dit), and excellent time-dependent dielectric breakdown. For instance, its gate leakage under flatband voltage (Vfb) -1 V is only 2.48 × 10–9 A/cm2, its minimum Dit reaches 5.1 × 1010 eV−1 cm−2, and its ten-year lifetime effective voltage can reach 3.62 V at a failure rate of 0.01%. Moreover, a GAA NS based I/O device with a healthy gate stack is successfully prepared using this low-temperature SiO2 interfacial layer and its gate leakage is below 1 × 10–13 A, approaching the detection limit. These above results indicate that this low-temperature RTO-grown SiO2 IL has excellent quality and can meet the requirements of GAA NSs I/O transistors. [ABSTRACT FROM AUTHOR]

The experiment was conducted to investigate the effect of different levels of guanidine acetic acid (GAA) in the basal diet on the antioxidant capacity and serum biochemical indexes of growing minks. A total of 120 growing shorthaired black minks (half in male and female) aged 65 days with similar body weight were randomly divided into six groups, with ten replicates in each group and one mink in each replicate. The feed in group I to group VI were supplemented with 0, 200, 400, 600, 800 and 1 000 mg/kg GAA, respectively, and group I was the control group. The test period was 71 days. The results showed that compared with the control group, the activity of T-SOD and GSH-Px in the serum and liver tissue of minks in the group IV and group V were significantly increased (P<0.05), the content of MDA was significantly decreased (P<0.05), and the T-AOC, activity of CAT and hydroxyl radical inhibition in the liver tissue of minks were significantly increased (P<0.05). The content of TP and ALB in the serum of male minks in the group IV, group V was significantly increased (P<0.05), while the activity of AKP, AST and ALT was significantly decreased (P<0.05). The content of TP and GLB in the serum of female minks in the group IV was significantly increased (P<0.05), while the activity of AST, ALT and AKP was significantly decreased (P<0.05). The study indicates that GAA supplementation in the basal diet can improve the antioxidant capacity and affect the biochemical indexes of growing minks. The supplemental level of 600 to 800 mg/kg shows a better effect. [ABSTRACT FROM AUTHOR]

Background: There are limited studies examining alcohol consumption in Gaelic Athletic Association (GAA) players. In a previous paper, we reported excess alcohol consumption, alcohol-related harms and binge drinking amongst elite GAA players. In that survey, the players were provided with an opportunity to provide comments on alcohol. This current study analyses these comments. Aims: The aim of this study was to provide a qualitative analysis of elite GAA players opinions on alcohol consumption, harms, behaviours and culture. Methods: An anonymous, web-based e-questionnaire was distributed to all registered adult elite (inter-county) GAA players. This analysed demographics, alcohol consumption, alcohol culture and alcohol-related harms. This paper is a thematic analysis of the players comments on alcohol in the GAA. Results: Seven hundred seventy-three of 3592 (21%) players responded. One hundred fifty-two respondents (21%) commented in the free text section of the survey regarding alcohol. One hundred eleven comments (73%) were suitable for analysis. Relevant themes were a pattern of abstinence and bingeing (n = 44), excess alcohol consumption (n = 40) and drinking bans contributing to a binge drinking culture (n = 37). There was a mixed attitude to alcohol sponsorship. Conclusion: These data show players recognise intermittent binge drinking with periods of abstinence and alcohol-related harms. Further initiatives regarding alcohol harm reduction merit consideration including prohibition of alcohol sponsorship, similar to the GAA's ban on gambling. [ABSTRACT FROM AUTHOR]

Abstract Background Pompe disease is a rare glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to glycogen deposition in multiple tissues. Infantile-onset Pompe disease (IOPD) patients present within the first year of life with profound hypotonia and hypertrophic cardiomyopathy. Treatment with enzyme replacement therapy (ERT) has significantly improved survival for this otherwise lethal disorder. This study aims to describe the clinical and molecular spectrum of Malaysian IOPD patients, and to analyze their long term treatment outcomes. Methods Seventeen patients diagnosed with IOPD between 2000 and 2020 were included in this retrospective cohort study. Clinical and biochemical data were collated and analyzed using descriptive statistics. GAA enzyme levels were performed on dried blood spots. Molecular analysis of the GAA gene was performed by polymerase chain reaction and Sanger sequencing. Structural modelling was used to predict the effect of the novel mutations on enzyme structure. Results Our cohort had a median age of presentation of 3 months and median age of diagnosis of 6 months. Presenting features were hypertrophic cardiomyopathy (100%), respiratory insufficiency (94%), hypotonia (88%), failure to thrive (82%), feeding difficulties (76%), and hepatomegaly (76%). Fourteen different mutations in the GAA gene were identified, with three novel mutations, c.1552-14_1552-1del, exons 2–3 deletion and exons 6–10 deletion. The most common mutation identified was c.1935C > A p.(D645E), with an allele frequency of 33%. Sixteen patients received ERT at the median age of 7 months. Overall survival was 29%. Mean age of death was 17.5 months. Our longest surviving patient has atypical IOPD and is currently 20 years old. Conclusions This is the first study to analyze the genotype and phenotype of Malaysian IOPD patients, and has identified the c.1935C > A p.(D645E) as the most common mutation. The three novel mutations reported in this study expands the mutation spectrum for IOPD. Our low survival rate underscores the importance of early diagnosis and treatment in achieving better treatment outcomes.

The aim of the current investigation was to examine the locomotor performance profile of elite ladies Gaelic football (LGF) players in relation to playing position and quarters of play. Thirty (n = 30) elite LGF players (age: 24 ± 4 years, height: 169 ± 5 cm, body mass: 61 ± 4 kg) were monitored using 10 Hz GPS technology (Playertek; Catapult Sports; Australia) resulting in 145 individual samples collected over 18 competitive matches across the 2021 and 2022 LGF seasons. Locomotor performance was determined across the following variables: total distance covered (TD, m), relative distance (m·min−1), high-speed running (HSR, ≥ 4.4 m·s−1), very high-speed running (VHSR, ≥ 5.5 m·s−1), relative HSR (RHSR; m·min−1), peak velocity (m·s−1), percentage peak velocity (%PeakV), accelerations (n; ≥ 3 m·s−2), and decelerations (n; ≤ −3 m·s−2). Data were classified based on playing position and quarter of play. The greatest TD was covered by half-backs, midfielders, and half-forwards, with these positions covering significantly greater distances than full-backs (p < 0.05). Similarly, half-backs, midfielders, and half-forwards covered the greatest high-speed distance (HSR). When running performance was analysed across quarters, a significant position by quarter interaction was observed for all running performance variables, except peak velocity and percentage peak velocity. A consistent trend for reduced locomotor performance was evident in the second and fourth quarters across all positional lines. The current data provide coaches with the position-specific locomotor requirements of LGF match-play, which can inform the design of training content for LGF players, along with match-day strategies. Given the reduction in locomotor performance observed across the match, performance staff may consider the use of nutritional interventions, rewarm-up strategies, or specific substitution policies to mitigate the decrement in locomotor performance observed across match-play.

Cardiac glycogen-autophagy (‘glycophagy’) is disturbed in cardiometabolic pathologies. The physiological role of cardiac glycophagy is unclear. Exercise induces transient cardiac glycogen accumulation. Thus, this study experimentally examined glycophagy involvement during recovery from an exhaustive exercise protocol. Peak myocardial glycogen accumulation in mice was evident at 2 h post-exercise, preceded by transient activation of glycogen synthase. At 4 and 16 h post-exercise, glycogen degradation was associated with decreased STBD1 (glycophagy tagging protein) and increased GABARAPL1 (Atg8 protein), suggesting that glycophagy activity was increased. These findings provide the first evidence that glycophagy is involved in cardiac glycogen physiologic homeostasis post-exercise.

Purpose: The current investigation aimed to examine the running performance of elite Ladies Gaelic football (LGF) match-play and establish the within game positional profile, in addition to the running performance of players across halves of play. Methods: GPS technology was used to examine the running performance of thirty-three (n = 33) elite LGF players (age; 23 ± 5 years, height; 173 ± 5 cm, body mass; 63 ± 4 kg). Across the duration of the observational period, one hundred and thirty-one (n = 131) individual samples were collected over 15 competitive matches. Data were classified based on positional line and across halves of play. Running performance was determined across the following performance variables of total distance covered (m) (TD), relative distance (m·min−1), HSR (≥ 4.4 m·s−1), RHSR (HSR; m·min−1), percentage HSR (% HSR), VHSR (≥ 5.5 m·s−1), peak velocity (m s−1), percentage peak velocity (% PeakV), accelerations (n; ≥ 3 m·s−2) and decelerations (n; ≤ − 3 m·s−2), Results: Independent of position the mean distance covered during match play was 7319 ± 1021 m which equates to a relative work rate of 116 ± 9 m·min−1. The high-speed distance of players was 1547 ± 432 m, which equates to a relative high-speed running distance of 25 ± 11 m·min−1. The maximal velocity of players was 7.17 ± 0.41 m·s−1 reflective of a relative maximal velocity of 86 ± 4 percent. The greatest distances were covered by half-backs, midfielders, and half-forwards, with these positions covering significantly greater distances than full-backs (p ≤ 0.05; ES: 0.59–1.25; small-moderate) and full-forwards (p ≤ 0.05; ES: 0.44–1.21; small-moderate). While TD and maximal velocity was shown not to change across halves of play, significant reductions (p ≤ 0.05) were observed across HSR (ES: 0.64–1.02; moderate), accelerations and decelerations (ES: 0.59–1.20; moderate). Conclusion: The current investigation is the first of its kind within elite LGF, the data within the investigation can aid the coaching process by allowing for the development of sport-specific training regimen specific to the positional needs of elite LGF players. [ABSTRACT FROM AUTHOR]

The Nanosheet Field Effect Transistor (NSFET) has been shown to be a viable candidate for sub-7-nm technology nodes. This paper assesses and compares the NSFET performance at elevated temperatures ranging from 250 to 2000C at both device and circuit levels. As the temperature increases from 250 to 2000C, the electron mobility is reduced by 68% due to the severe scattering mechanism. It is observed that the electrical performance degraded with rise in temperature. Moreover, the temperature variations on analog/RF FOMs like gm, intrinsic gain (Av0), cut-off frequency (fT), intrinsic delay (τ ), transconductance frequency product (TFP), gain bandwidth product (GBW), gain frequency product (GFP), and gain transconductance frequency product (GTFP) are studied and analyzed. In this move, at high temperatures, the degradation in analog/RF metrics is observed due to the reduction in carrier mobility. Further, the circuit-level performance is demonstrated at different temperatures. As temperature increases from 250 to 2000C, 91% and 49% degradation in propagation delay and gain is noticed for inverter, respectively. Further, there is a degradation of 1.6 × in oscillation frequency (fosc) is noticed for the 3-stage ring oscillator when the temperature increased from 250 to 2000C. The circuit level performance also deteriorated owing to the degradation of device's performance at higher temperatures. Thus, the analyses will give deep insights into the performance of NSFET at both device and circuit levels at elevated temperatures. [ABSTRACT FROM AUTHOR]

Presently deep learning (DL) techniques are massively used in the semiconductor industry. At the same time, applying a deep learning approach for small datasets is also an immense challenge as larger dataset generation needs more computational time-cost factors for technology computer-aided design (TCAD) simulation. In this paper, to overcome the aforesaid issue, a hybrid DL-aided prediction of electrical characteristics of the multichannel devices induced by work function fluctuation (WKF) with a smaller dataset is proposed. For the first time, an amalgamation approach of two deep learning algorithms (i.e.1D-CNN and LSTM) is implemented for all four channels (1 to 4 channels) of gate-all-around (GAA) silicon Nanosheet and Nanofin MOSFETs (NS-FETs and NF-FETs). The proposed joint learning framework combines a one-dimensional convolutional neural network (1D-CNN) with long short-term memory (LSTM) model. In this architecture, CNN can extract the features efficiently from the input WKF, and LSTM identifies the historical sequence of the captured features of the input regression data. To illustrate the excellency of the proposed approach, a comparative study of our hybrid model along with three individual DL models i.e. 1D-CNN and LSTM including a baseline multilevel perceptron (MLP) model are demonstrated for a promising small dataset (i.e.1100 samples). The results indicate a superior prediction of 1D-CNN-LSTM in terms of root mean square error (RMSE) with an average value of $\mathrm {1.7943 X}{10}^{-7}$ and $\text{R}^{2}$ Score with an average value of 96.18% within the shortest time span in contrast to the other three algorithms. Finally, it can be quantified according to the evaluation and performance that hybrid methodology not only adopts the complexity of both NS- and NF-FETs, but also estimates the characteristics of all four channels of it efficiently with a smaller dataset, lesser time span, and reduced computational cost.

Pompe disease is caused by deficiency of acid α-glucosidase (GAA), resulting in glycogen accumulation in various tissues, including cardiac and skeletal muscles and the central nervous system (CNS). Enzyme replacement therapy (ERT) improves cardiac, motor, and respiratory functions but is limited by poor cellular uptake and its inability to cross the blood-brain barrier. Previously, we showed that hematopoietic stem cell (HSPC)-mediated lentiviral gene therapy (LVGT) with codon-optimized GAA (LV-GAAco) caused glycogen reduction in heart, skeletal muscles, and partially in the brain at high vector copy number (VCN). Here, we fused insulin-like growth factor 2 (IGF2) to a codon-optimized version of GAA (LV-IGF2.GAAco) to improve cellular uptake by the cation-independent mannose 6-phosphate/IGF2 (CI-M6P/IGF2) receptor. In contrast to LV-GAAco, LV-IGF2.GAAco was able to completely normalize glycogen levels, pathology, and impaired autophagy at a clinically relevant VCN of 3 in heart and skeletal muscles. LV-IGF2.GAAco was particularly effective in treating the CNS, as normalization of glycogen levels and neuroinflammation was achieved at a VCN between 0.5 and 3, doses at which LV-GAAco was largely ineffective. These results identify IGF2.GAA as a candidate transgene for future clinical development of HSPC-LVGT for Pompe disease.

Background: Pompe disease is a rare glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to glycogen deposition in multiple tissues. Infantile-onset Pompe disease (IOPD) patients present within the first year of life with profound hypotonia and hypertrophic cardiomyopathy. Treatment with enzyme replacement therapy (ERT) has significantly improved survival for this otherwise lethal disorder. This study aims to describe the clinical and molecular spectrum of Malaysian IOPD patients, and to analyze their long term treatment outcomes. Methods: Seventeen patients diagnosed with IOPD between 2000 and 2020 were included in this retrospective cohort study. Clinical and biochemical data were collated and analyzed using descriptive statistics. GAA enzyme levels were performed on dried blood spots. Molecular analysis of the GAA gene was performed by polymerase chain reaction and Sanger sequencing. Structural modelling was used to predict the effect of the novel mutations on enzyme structure. Results: Our cohort had a median age of presentation of 3 months and median age of diagnosis of 6 months. Presenting features were hypertrophic cardiomyopathy (100%), respiratory insufficiency (94%), hypotonia (88%), failure to thrive (82%), feeding difficulties (76%), and hepatomegaly (76%). Fourteen different mutations in the GAA gene were identified, with three novel mutations, c.1552-14_1552-1del, exons 2–3 deletion and exons 6–10 deletion. The most common mutation identified was c.1935C > A p.(D645E), with an allele frequency of 33%. Sixteen patients received ERT at the median age of 7 months. Overall survival was 29%. Mean age of death was 17.5 months. Our longest surviving patient has atypical IOPD and is currently 20 years old. Conclusions: This is the first study to analyze the genotype and phenotype of Malaysian IOPD patients, and has identified the c.1935C > A p.(D645E) as the most common mutation. The three novel mutations reported in this study expands the mutation spectrum for IOPD. Our low survival rate underscores the importance of early diagnosis and treatment in achieving better treatment outcomes. [ABSTRACT FROM AUTHOR]

Gate-all-around (GAA) structures are important for future logic devices and 3D-DRAM. Inner-spacer cavity etching and channel release both require selective etching of Si0.7Ge0.3. Increasing the number of channel-stacking layers is an effective way to improve device current-driving capability and storage density. Previous work investigated ICP selective etching of a three-cycle Si0.7Ge0.3/Si multilayer structure and the related etching effects. This study focuses on the dry etching of a 15-cycle Si0.7Ge0.3/Si multilayer structure and the associated etching effects, using simulation and experimentation. The simulation predicts the random effect of lateral etching depth and the asymmetric effect of silicon nanosheet damage on the edge, both of which are verified by experiments. Furthermore, the study experimentally investigates the influence and mechanism of pressure, power, and other parameters on the etching results. Research on these etching effects and mechanisms will provide important points of reference for the dry selective etching of Si0.7Ge0.3 in GAA structures. [ABSTRACT FROM AUTHOR]

Introducción: la enfermedad de Pompe (EP) o glucogenosis tipo II es una enfermedad autosómica recesiva causada por mutaciones en el gen GAA que codifica para la proteína alfa-1,4-glucosidasa. Su deficiencia lleva a un almacenamiento anormal de glucógeno en los lisosomas de varias células, a través de los diferentes tejidos, lo que causa un compromiso musculoesquelético predominante. Contenidos: los fenotipos de la enfermedad dependen de las variantes genéticas y de los niveles de la actividad enzimática residual. La enfermedad se presenta como EP de inicio infantil, EP de inicio tardío y EP intermedio, por lo que es de suma importancia su diagnóstico temprano, por medio de estudios moleculares como la secuenciación de Sanger y la secuenciación de nueva generación. Conclusiones: se ha demostrado, mediante diferentes estudios, que las variaciones genéticas pueden diferir entre etnias, y es importante su caracterización molecular para determinar el tratamiento más adecuado, de acuerdo con el estado del material inmunológico de reacción cruzada (CRIM).

This study aimed to investigate the effect of guanidinoacetic acid (GAA) with different protein levels in feed on intestinal histomorphology, serum biochemistry, and meat quality of broiler chicken. GAA is the only direct precursor of creatine and is involved in the synthesis of bioenergy cellular. This research used 1.176 day-old chicks of the Lohmann Indian River strain that were reared for 35 days. The supplementation effect was investigated using six treatments, i.e., two levels of feed protein and three levels of GAA, with seven replications. Broiler chickens were fed with 23% and 21% crude pro-tein during the pre-starter phase, 21% and 19% during the starter phase, and 19% and 17% during the finisher phase, with a GAA addition of 0 g/ton, 600 g/ton, and 1200 g/ton, respectively. The result showed GAA supplementation with different protein levels reduced triglyceride (P0,05). In conclusion, GAA supplementation in different level protein diets increased the surface area of the microvilli, pH of breast meat, reduce se-rum cholesterol and triglycerides, without affecting the chemical quality of broiler meat.

TCAD simulation using Silvaco software has shown that the 3G_DFM, which has SG1 (Select Gate 1), PL (Plate Line Gate), and SG2 (Select Gate 2) between SL (Source Line) and BL (Bit Line), has a long retention time of 100ms at 85 °C, and a robust disturbance shield which is a thousand times BL stress. The two select gates SG1 and SG2 protect the recombination of holes in the FB (Floating Body) at the SL and BL pn-junctions, and shield the BL stress arising during other page operations, which leads to the GIDL (Gate Induced Drain Leakage) current.

This research work uses sp3d5s* tight-binding models to design and analyze the structural properties of group IV and III-V oriented, rectangular Silicon (Si) and Gallium Arsenide (GaAs) Nanowires (NWs). The electrical characteristics of the NWs, which are shielded with Lanthanum Oxide (La2O3) material and the orientation with z [001] using the Non-Equilibrium Green Function (NEGF) method, have been analyzed. The electrical characteristics and the parameters for the multi-gate nanowires have been realized. A nanowire comprises a heavily doped n+ donor source and drains doping and n-donor doping at the channel. The specified nanowire has a gate length and channel length of 15 nm each, a source-drain device length LSD = 35 nm, with La2O3 as 1 nm (gate dielectric oxide) each on the top and bottom of the core material (Si/GaAs). The Gate-All-Around (GAA) Si NW is superior with a high (ION/IOFF ratio) of 1.06 × 109, and a low leakage current, or OFF current (IOFF), of 3.84 × 10−14 A. The measured values of the mid-channel conduction band energy (Ec) and charge carrier density (ρ) at VG = VD = 0.5 V are −0.309 eV and 6.24 × 1023 C/cm3, respectively. The nanowires with hydrostatic strain have been determined by electrostatic integrity and increased mobility, making them a leading solution for upcoming technological nodes. The transverse dimensions of the rectangular nanowires with similar energy levels are realized and comparisons between Si and GaAs NWs have been performed. [ABSTRACT FROM AUTHOR]

Introduction. Pompe Disease is a rare, autosomal recessive, lysosomal disorder caused by deficiency of alpha glucosidase (GAA). It leads to the accumulation of glycogen in body tissues, with severe myopathy and cardiomegaly as a hallmark of the classic infantile form. Non-classical, or Late Onset Pompe Disease (LOPD) manifests after 12 months of age or in adulthood. Material and methods. The clinical heterogeneity of LOPD causes delay in diagnosis and pharmacological treatment. In the Polish population, it is still underdiagnosed, and the time from onset to diagnosis remains a cause for concern. Clinical implications. Although typically patients present with proximal muscle weakness, high CK or early respiratory insufficiency, they can also suffer from multiple symptoms from other organs. Patients may present with arrhythmias, vascular abnormalities including aneurysms or dilative arteriopathy, gastric or urinary symptoms, or musculoskeletal pathologies. Results. A high index of suspicion among neurologists consulting internal medicine wards would aid early diagnosis of LOPD, while a multidisciplinary approach with the involvement of other specialists can reduce the risk of complications and improve the prognosis for LOPD patients. Patients who manifest with musculoskeletal and respiratory symptoms are prone to be diagnosed sooner than individuals with non-muscular symptoms, and therefore it is important to raise awareness of other manifestations of this disease. [ABSTRACT FROM AUTHOR]

• Capacitorless DRAM Performance according to the Junctionless GAA Structure Parameter and Stacked GAA. • Channel Thickness has a significant impact on Sensing Margin. • Secure 100 ms improved Retention Time at 6 nm Channel Thickness at Single GAA Structure. • The Contrast of Sensing Margin and Retention Time in Staked Nanosheet Structure. The characteristic comparison of the capacitor-less DRAMs in the structural form variation is investigated. Based on the simulation results of the three basic structures, such as circular, square, and rectangular nanosheets, the gate length (L g), channel thickness (T si), and width of the nanosheet (W si) are considered as the main factors in design and the characteristic variations are verified according to the junctionless (JL) gate-all-around (GAA) geometry factors. The channel thickness is a major factor that has a major influence on the sensing margin and the retention time, which are important characteristics of DRAM. The thinner the thickness, the more deteriorated the sensing margin is confirmed. Retention time is due to the influence of the electric field distribution of the JL GAA structure, resulting in differences in structure. Finally, the rectangular type nanosheet is implemented in the stacked structure. As the number of stacks increases, the effective channel width increases compared to the layout footprint. In addition, by stacking vertically, the area where holes can be stored increases. Therefore, the sensing margin tends to increase as the number of stacks increases. However, the difference in diffusion due to the difference in the initially stored hole density, the retention time deteriorates as the number of stacks increases. [ABSTRACT FROM AUTHOR]

Background: Gaelic Athletic Association (GAA) games are collision sports played at an amateur level, which represent the most popular sports played on the island of Ireland. Each year, many GAA players in Ireland require surgical stabilization with either arthroscopic Bankart repair (ABR) or open Latarjet (OL) procedures in the setting of anterior shoulder instability. The purpose of this study was to evaluate the clinical outcomes, recurrence, and return to play (RTP) in athletes who play GAA games having undergone surgical stabilization with either ABR or OL procedures in the setting of anterior shoulder instability. Methods: A retrospective review of all patients with anterior shoulder instability whom had stabilization with either ABR or OL under a single surgeon between 2012 and 2018 was performed. Patients who were athletes partaking in GAA sports were followed up by chart review and telephone survey to assess their clinical outcomes including satisfaction, pain as measured on the visual analog scale score, the Subjective Shoulder Value, recurrence, complications, and revision surgeries. In addition, RTP rates, time to RTP, level of RTP, and Shoulder Instability–Return to Sport after Injury scores were evaluated. Results: A total of 200 GAA athletes (194 males) with a mean age of 23.9 ± 6.1 years with mean follow-up of 50.4 ± 24 months were included in this study. A total of 98.1% patients were satisfied with their procedure at the latest follow-up, with an overall recurrence rate of 5%. A total of 6.5% of athletes required revision surgery, of whom 4% required revision stabilization (all of whom had recurrence). The overall rate of RTP was 88% at mean 6.0 ± 1.7 months postoperatively, with 75% of athletes returning at the same or higher levels than their preinjury level. There were no significant differences for all outcome measures analyzed between patients who had ABR or OL procedures. Conclusion: GAA athletes with anterior shoulder instability treated with either ABR or OL procedures report excellent clinical outcomes at medium-term follow-up, with high satisfaction rates, excellent functional outcomes, and high rates of RTP. Furthermore, this cohort demonstrates low rates of recurrence after stabilization with few requiring revision surgery.

The aim of this study was to investigate whether guanidine acetic acid (GAA) yields a response in rapid-growing lambs depending on forage type. In this study, seventy-two small-tailed Han lambs (initial body weights = 12 ± 1.6 kg) were used in a 120-d feeding experiment after a 7-d adaptation period. A 2 × 3 factorial experimental feeding design was applied to the lambs, which were fed a total mixed ration with two forage types (OH: oaten hay; OHWS: oaten hay plus wheat silage) and three forms of additional GAA (GAA: 0 g/kg; UGAA: Uncoated GAA, 1 g/kg; CGAA: Coated GAA, 1 g/kg). The OH diet had a greater dry matter intake, average daily gain, and hot carcass weight than the OHWS diet. The GAA supplementation increased the final body weight, hot carcass weight, dressing percentage, and ribeye area in the longissimus lumborum. Meanwhile, it decreased backfat thickness and serum triglycerides. Dietary GAA decreased the acidity of the meat and elevated the water-holding capacity in mutton. In addition, the crude protein content in mutton increased with GAA addition. Dietary GAA (UGAA or CGAA) might be an effective additive in lamb fed by different forage types, as it has potential to improve growth performance and meat quality. [ABSTRACT FROM AUTHOR]

In elite Gaelic football, body composition is commonly assessed by methods, such as skinfold equations and dual-energy X-ray absorptiometry (DXA) with estimates of body fat used to evaluate and monitor nutrition and training programmes. The aim of this study was to assess the accuracy and variability of the existing skinfold equations in predicting body fat % (BF%) and fat mass (FM) as compared to DXA in elite Gaelic football players and to derive novel sport-specific skinfold equations. Body composition in thirty-two elite outfield Gaelic football players (23.4 ± 3.3 years; 83.6 ± 7.2 kg; 183.5 ± 6.4 cm) was assessed via skinfold thickness at 7 sites and DXA. A standardised testing protocol was followed for both methods of assessment. Male-specific prediction equations commonly used in Gaelic football research to estimate BF% (Durnin and Womersley, Evans, Lohman, Reilly and Withers) and FM (Stewart) were selected. Using the skinfold data collected, Gaelic football prediction equations were developed relative to DXA. All the existing skinfold equations underestimated BF% (8.9–11.8%) and FM (6.8 kg) by varying magnitudes relative to DXA (15.2%; 11.8 kg). Gaelic football prediction equations for BF% and FM were designed and accounted for 69% and 76% variance in DXA derived BF% and FM, respectively. The existing skinfold equations demonstrated large variation in estimates of BF% and FM in elite Gaelic football players as compared to DXA, causing the potential for misleading comparisons and inappropriate intervention. The Gaelic football equations offer sport-specific estimates of BF% and FM and greater consistency as compared to the selected equations when evaluating nutrition and training strategies. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of guanidinoacetic acid (GAA) with different protein levels in feed on intestinal histomorphology, serum biochemistry, and meat quality of broiler chicken. GAA is the only direct precursor of creatine and is involved in the synthesis of bioenergy cellular. This research used 1.176 day-old chicks of the Lohmann Indian River strain that were reared for 35 days. The supplementation effect was investigated using six treatments, i.e., two levels of feed protein and three levels of GAA, with seven replications. Broiler chickens were fed with 23% and 21% crude protein during the pre-starter phase, 21% and 19% during the starter phase, and 19% and 17% during the finisher phase, with a GAA addition of 0 g/ton, 600 g/ton, and 1200 g/ton, respectively. The result showed GAA supplementation with different protein levels reduced triglyceride (P<0,05), cholesterol levels in serum (P<0,05), increased surface area of the microvilli (P<0,05), pH of breast meat (P<0,05), but did not affect the chemical quality of breast meat (P>0,05). In conclusion, GAA supplementation in different level protein diets increased the surface area of the microvilli, pH of breast meat, reduce serum cholesterol and triglycerides, without affecting the chemical quality of broiler meat. [ABSTRACT FROM AUTHOR]

Abstract Background Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease. Results From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years. Conclusions The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.

Pompe disease (PD) is a rare, autosomal recessive, inherited, and progressive metabolic disorder caused by α-glucosidase defect in lysosomes, resulting in abnormal glycogen accumulation. Patients with PD characteristically have multisystem pathological disorders, particularly hypertrophic cardiomyopathy, muscle weakness, and hepatomegaly. Although the pathogenesis and clinical outcomes of PD are well-established, disease-modeling ability, mechanism elucidation, and drug development targeting PD have been substantially limited by the unavailable PD-relevant cell models. This obstacle has been overcome with the help of induced pluripotent stem cell (iPSC) reprogramming technology, thus providing a powerful tool for cell replacement therapy, disease modeling, drug screening, and drug toxicity assessment. This review focused on the exciting achievement of PD disease modeling and mechanism exploration using iPSC.

Septoria leaf blotch (SLB) disease caused by Mycosphaerella graminicola affect wheat plants causing serious losses in produced yield. Evaluation the potentiality of certain antagonists and growth regulators to suppress the SLB disease severity was performed under natural field conditions for two successive growing seasons whereas three wheat cultivars were sprayed with Pseudomonas fluorescens and Trichoderma harzianum as well as the growth regulators Gibberellic Acetic Acid, Indole Acetic Acid. All applied treatments showed their activity for decreasing the disease severity. The lowest disease severity and highest grains yield was recorded at fungicide Amistar treatment followed by growth regulators GAA, IAA and then the antagonists, P. fluorescens and T. harzianum in descending order. Based on the present finding, it could be concluding that the use of plant growth regulators as well as antagonists as foliar spray on wheat plants revealed reduction in SLB disease severity and increase in produced yield in return [ABSTRACT FROM AUTHOR]

To meet the scaling targets and continue with Moore's Law, the transition from FinFET to Gate-All-Around (GAA) nanosheet Field Effect Transistors (FETs) is the necessity for low-power to high-performance applications in upcoming nodes. In this work, we benchmark nanosheet FET against FinFET of comparable dimensions. Due to increased effective width, stacked nanosheet FET offers improved DC and analog/RF performance over multi-fin FinFET. The impact of geometrical parameter variations on the performance of stacked Si nanosheet FET is investigated for sub-3 nm technology node. We have considered nanosheet thickness (NST), nanosheet width (NSW), number of channels and oxide thickness (tox) as the sources of variability. The simulation carried out on Genius TCAD device simulator reports that higher NST, higher NSW, more number of channels and thinner oxide results in improved device driving capability, ON-current (Ion), transconductance (gm), intrinsic delay and cut-off frequency (ft). OFF-current (Ioff), ON-current to OFF-current ratio (Ion/Ioff), immunity against short channel effects (SCEs) and gate capacitance (Cgg) can be improved using lower NST, lower NSW, lesser number of channels and thinner oxide. However, threshold voltage (Vth) roll-off is more pronounced for thinner and narrower sheets with a thin oxide. [ABSTRACT FROM AUTHOR]

This paper critically examines the evolving state of sport governance with an applied examination of the Gaelic Athletic Association (GAA) in Ireland. The challenge, which this article considers, is how this transformation becomes realised in an organisation, like the GAA, whilst remaining broadly aligned to an amateur and volunteer-led ethos, still representative of its membership at large and continuing to be broadly equitable in its funding and other fiscal policies. At a governance level it raises specific questions about the role of elected boards, their backgrounds, competencies, scope, and purpose as this strategic 'step change' becomes embedded and, inevitably, poses many challenging questions. Put simply, if the direction of an organisation changes, requiring new and different attributes on behalf of those governing it, what is the most effective way to ensure this happens within specific cultural constraints and what are the associated challenges if it does not achieve this outcome? [ABSTRACT FROM AUTHOR]

Nanosheet Field Effect Transistor (NSFET) is a viable contender for future scaling in sub-7-nm technology. This paper provides insights into the variations of DC FOMs for different geometrical configurations of the NSFET. In this script, the DC performance of 3D GAA NSFET is analyzed by varying the device's width and thickness. Moreover, the gate length is scaled from 20 nm to 5 nm to check for the device suitability for continuous scaling in logic applications. The thickness and width of each nanosheet are varied in the range of 5 to 9 nm and 10 to 50 nm, respectively, to analyze the performance dependency on the geometry of the device. The impact of geometry of NSFET on various DC performance metrics like transfer characteristics, sub-threshold swing (SS), on current (ION), off current (IOFF), switching ratio (ION/IOFF), threshold voltage (Vth), and drain induced barrier lowering (DIBL) are studied. On top of that, the device's electrical characteristics are analyzed for a wide range of temperatures from -43oC to 127oC to identify the temperature compensation point and is observed at VGS = 0.55 V and ID = 3.86 × 10-6 A. Furthermore, the vital process parameter, work function variations on transfer characteristics of the device is analyzed. Moreover, the analyses reveal that, for sub -7 nm, the NSFET is a potential device for high performance and suitable for logic applications. [ABSTRACT FROM AUTHOR]

Alglucosidase alpha is an orphan drug approved for enzyme replacement therapy (ERT) in Pompe disease (PD); however, its efficacy is limited in skeletal muscle because of a partial blockage of autophagic flux that hinders intracellular trafficking and enzyme delivery. Adjunctive therapies that enhance autophagic flux and protect mitochondrial integrity may alleviate autophagic blockage and oxidative stress and thereby improve ERT efficacy in PD. In this study, we compared the benefits of ERT combined with a ketogenic diet (ERT-KETO), daily administration of an oral ketone precursor (1,3-butanediol; ERT-BD), a multi-ingredient antioxidant diet (ERT-MITO; CoQ10, α-lipoic acid, vitamin E, beetroot extract, HMB, creatine, and citrulline), or co-therapy with the ketone precursor and multi-ingredient antioxidants (ERT-BD-MITO) on skeletal muscle pathology in GAA-KO mice. We found that two months of 1,3-BD administration raised circulatory ketone levels to ≥1.2 mM, attenuated autophagic buildup in type 2 muscle fibers, and preserved muscle strength and function in ERT-treated GAA-KO mice. Collectively, ERT-BD was more effective vs. standard ERT and ERT-KETO in terms of autophagic clearance, dampening of oxidative stress, and muscle maintenance. However, the addition of multi-ingredient antioxidants (ERT-BD-MITO) provided the most consistent benefits across all outcome measures and normalized mitochondrial protein expression in GAA-KO mice. We therefore conclude that nutritional co-therapy with 1,3-butanediol and multi-ingredient antioxidants may provide an alternative to ketogenic diets for inducing ketosis and enhancing autophagic flux in PD patients. [ABSTRACT FROM AUTHOR]

Purpose: Injury can exacerbate mental health issues in athletes. However, the prevalence of mental health issues is not equivalent to the rate of professional help-seeking, with reluctance to seek-help acknowledged as one of the greatest obstacles in efficient management of mental health issues. The current study aimed to examine perceived barriers and facilitators to professional mental health help-seeking in elite male and female Gaelic footballers post-injury. Methods: Male (n = 14) and female (n = 12) elite Gaelic footballers, with a history of moderate or severe injury, were recruited to participate in a focus group. Group discussions began with a written task where participants noted perceived barriers to help-seeking followed by a group discussion of these barriers. Following discussion, participants ranked identified barriers in order of those perceived as most important in stopping a player from seeking help when experiencing mental health issues post-injury. All three tasks were repeated for help-seeking facilitators. Focus groups were audiotaped, transcribed and thematically analyzed. Results: Lack of education, stigma, negative attitudes to help-seeking and accessibility issues were identified as key barriers to help-seeking among elite Gaelic footballers. Education, the attitudes and actions of others and accessibility were perceived as factors facilitating help-seeking. Conclusions: Given the negative psychological responses that can accompany injury, there is a need for facilitation and encouragement of help-seeking among players experiencing mental health issues post-injury. Interventions for reducing the barriers to help-seeking identified in the current study are necessary. [ABSTRACT FROM AUTHOR]

This paper proposes a Dynamic Flash Memory (DFM) (Sakui and Harada, 2020; 2021 [1,2]) with double storage gates and one select gate based on FinFET and Surrounding Gate Transistor (SGT) (Takato et al., 1988 [3]) architectures. Like DRAM (Dennard, 1967 [4]), refresh is required, but fast block refresh improves the duty ratio. Analogous to Flash (Masuoka, 1981 [5]), three basic operations of “0” Erase, “1” Program, and Read are necessary, but the ability to carry out Read-While-Erase (RWE), and Program-While-Erase (PWE) operations in the background results in a faster system.

Ganoderma lucidum , a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (p ＜0.01 or p ＜0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (p ＜0.01 or p ＜0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (p ＜0.01). GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy. [Display omitted] • GAA alleviates MPP+-induced neurotoxicity in vitro. • GAA mitigates MPTP-induced motor dysfunction and dopaminergic neurons loss in vivo. • GAA inhibits MPP+/MPTP-induced neurons ferroptosis in vitro and in vivo. • GAA inhibits MPP+/MPTP-induced neurons ferritinophagy in vitro and in vivo. • GAA suppresses NCOA4-mediated ferritinophagy to inhibit dopaminergic neuron ferroptosis to alleviate PD. [ABSTRACT FROM AUTHOR]