bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of CD44 Variant Isoforms in Normal and Neoplastic Cells of the Lung
Authors: Washimi Osuke , Ueda Ryuzo , Ariyoshi Yutaka , Suyama Mot okazu , Seki Tsuneo , Takahashi Toshitada , Takahashi Takashi
Published: August 2005

CD44 is a cell surface receptor that has been implicated in lymphocyte homing, hematopoiesis, cell migration and possibly also tumor metastasis. In the present study, expression of CD44 variant (CD44v) isoforms was analyzed in 23 lung cancer specimens together with corresponding normal lung tissues by Southern blot analysis coupled with reverse transcription‐polynterase chain reaction amplification. We found that CD44v isoforms were expressed in all lung cancer specimens, suggesting a possible role in the establishment of metastases by these highly malignant tumors, but normal tissues were also positive. This is in marked contrast to the previous reports of essentially negligible expression of CD44v isoforms in normal colon and breast, and suggests a physiological function in the lung.
Simultaneous Expression of Type IX Collagen and an Inhibin‐related Antigen in Proliferative Myoepithelial Cells with Pleomorphic Adenoma of Canine Mammary Glands
Authors: Arai Katsuhiko , Uehara Kohkichi , Nagai Yutaka
Published: August 2005

To identify an alcian blue‐positive component expressed in the early stage of mammary mixed tumor and to pursue the possible involvement of a tumorigenic inducing factor, monoclonal antibodies to type IX collagen were generated and used to investigate the immnnohistochemical kinetics of type IX collagen expression by the myoepithelial cell‐derived chondrocyte‐Uke cells during the development of chondrometaplasia. We also examined the expression of inhibin‐related antigen using antibodies to a synthetic peptide spanning amino acids 1–30 of the inhibin α chain. At the earliest stage of chondrometaplasia, where myoepithelial cells began to proliferate inside the basement membrane, the cells expressed type IX collagen together with an inhibin‐related antigen which was immunoreactive with the anti‐inhibin peptide antibodies. The expression of the inhibin‐related antigen was also demonstrated in normal embryonic chondrocytes and myoblasts, but was much less strong in mature chondrocytes and myotubes, strongly suggesting that the inhibin‐related antigen is involved in the development of chondrocytes and myoblasts from undifferentiated mesenchymal cells as well as proliferating myoepithelial cells as a chondro‐progenitor cell in the mammary mixed tumor. The pathophysiological significance of type IX collagen expression as a possible cell marker of the progenitor cell in myoepithelial cell‐related chondrometaplasia is also discussed.
Allelic Loss at the Tuberous Sclerosis (Tsc2) Gene Locus in Spontaneous Uterine Leiomyosarcomas and Pituitary Adenomas in the Eker Rat Model
Authors: Kubo Yoshiaki , Kikuchi Yasushi , Mitani Hiroaki , Kobayashi Etsuko , Kobayashi Toshiyuki , Hino Okio
Published: August 2005

Hereditary renal carcinomas (RCs) develop in virtually all Eker rats by the age of one year. Investigation of extra‐renal primary tumors co‐occurring in Eker rats late in life (at 2 years) additionally revealed enhanced development of hemangiosarcomas of the spleen, uterine leiomyosarcomas and pituitary adenomas, although the demonstrated predilection for these extra‐renal tumors was not as complete as with RCs. We identified the germline mutated tuberous sclerosis (Tsc2) gene as the predisposing Eker gene and revealed the tumor suppressor nature of Tsc2 gene function in renal carcinogenesis. In the present study, we examined allelic loss at the Tsc2 gene locus in uterine leiomyosarcomas and pituitary adenomas developing in hybrid F1 rats carrying the Eker mutation as well as in pituitary adenomas from non‐carrier rats. We detected loss of heterozygosity in 4 of 11 uterine leiomyosarcomas (36%) and 11 of 31 pituitary adenomas (35%) from Eker rats but in none of 9 pituitary adenomas from non‐carrier rats (P<0.05), suggesting that inactivation of the Tsc2 gene is also a critical event in the pathogenesis of these extra‐renal tumors. Our present data indicate that there might be different pathways for tumorigenesis of pituitary adenomas between Eker and non‐carrier rats.
Chemoprevention by Pravastatin, a 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A Reductase Inhibitor, of N‐Methyl‐N‐nitrosourea‐induced Colon Carcinogenesis in F344 Rats
Authors: Narisawa Tomio , Morotomi Masami , Fukaura Yoko , Hasebe Makiko , Ito Michiko , Aizawa Rika
Published: August 2005

A potential chemopreventive action of pravastatin (Pr), a 3‐hydroxy‐3‐methylglutaryl‐coenzyme A redutase inhibitor, on colon carcinogenesis was evaluated in F344 rats. All rats at 7 weeks of age received an intrarectal dose of 2 mg of N‐methyl‐N‐nitrosourea 3 times weekly for 2 weeks in experiment I (2 groups of 16 rats each), and for 3 weeks in experiment II (4 groups of 30 rats each). They were given drinking water containing 0 ppm (control) or 200 ppm Pr during weeks 1 to 40 in experiment I, and containing 0 ppm (control), 25 ppm, 5 ppm and 1 ppm Pr during weeks 4 to 40 in experiment II. The body weight gains, and food and water intakes were similar in all the groups. The incidence of colon carcinomas at termination of the experiment at week 40 was not different in the 200 ppm Pr and control groups in experiment I (63% vs. 69%), while it was significantly lower in the 25 ppm and 5 ppm groups, but not in the 1 ppm Pr group, compared with the control group in experiment II (50%, 48%, and 77% vs. 80%). This inhibitory effect of Pr against colon carcinogenesis was not related to the cholesterol‐lowering effect of this agent. We postulate that Pr inhibits the promotion stage of colon carcinogenesis, perhaps through modulation of cholesterol synthesis in situ in the colonic mucosa, thereby suppressing farnesyl isoprenylation of growth‐regulating proteins such as p21 ras.
Family History‐related Risk of Gastric Cancer in Japan: A Hospital‐based Case‐Control Study
Authors: Nagase Hirofumi , Ogino Keiki , Yoshida Isao , Matsuda Hiroto , Yoshida Masami , Nakamura Hiroyuki , Dan Shigun , Ishimaru Masanori
Published: August 2005

In Japan, there have been a few reports on the familiar factors of gastric cancer (GC)and on the GC risk related to family history (FH) at other cancer sites. We analyzed the association between GC occurrence and a positive FH of cancer of the stomach and of other sites in a hospital‐based case‐control study. The subjects included cases histologically confirmed as incident cancer of the stomach (n=136; 86 male and 50 female patients) and sex and age (± 1 year)‐matched controls. GC risk was high when a subject had a parental history of GC [Mantel‐Haenszel odds ratio adjusted for sex and age (OR) =2.3; 95% confidence interval (95%CI):1.1–5.0]. GC risk was almost unity for a cancer FH of any other cancer site, even among closer relatives, suggesting little or no contribution to GC occurrence. The familial occurrence of GC found in this study suggests the existence of a genetic susceptibility to cancer of the stomach. Further, females tended to show higher GC risks than males, when reporting an affected mother (OR=6.0; 95%CI:1.1–31.4 and OR=1.4; 95%CI:0.4–4.8, respectively), whereas males showed a slightly higher risk than females when reporting an affected father (OR=2.4; 95%CI:0.8–7.5 and OR=2.3; 95%CI:0.4–15.6, respectively). This suggests a possible gender difference in how environmental factors influence GC occurrence. The development of gastric tumors seems to be due to a complex and unknown interaction between environmental and genetic factors.
Intragenic Tsc2 Somatic Mutations as Knudson's Second Hit in Spontaneous and Chemically Induced Renal Carcinomas in the Eker Rat Model
Authors: Kobayashi Toshiyuki , Urakami Shinji , Hirayama Youko , Yamamoto Toshiki , Nishizawa Masae , Takahara Tomoko , Kubo Yoshiaki , Hino Okio
Published: August 2005

We searched for the rat homologue of the human tuberous sclerosis (TSC2) gene mutations in loss of heterozygosity (LOH)‐negative Eker rat renal carcinomas (RCs) by polymerase chain reactionsingle‐strand conformational polymorphism (PCR‐SSCP) analysis using 45 primer sets covering all 41 coding exons and one leader exon including splicing donor/acceptor sites. We have identified intragenic somatic mutations in 7 of 21 spontaneous RCs, including one cell line (33%), and in 3 of 9 (33%) N‐ethyl‐N‐nitrosourea (ENU)‐induced LOH‐negative RCs. Interestingly, five mutations in the spontaneous RCs were either deletion or duplication (5/7=71%). In contrast, all three in ENU‐induced RCs were base substitutions (3/3 = 100%), as expected. Thus, a qualitative difference in the second hit might exist between spontaneous and ENU‐induced mutations (e.g., deletion or duplication versus point mutation). By a direct cloning approach utilizing the restriction length difference caused by germline insertional mutation or reverse transcriptase‐PCR analysis in two applicable cases, we could clearly show the presence of intragenic somatic mutations in the second copy (wild‐type) of the Tsc2 gene. This is the first demonstration at the DNA sequence level of the validity of Knudson's two‐hits hypothesis in the Tsc2 gene.
Regulation of Vimentin Expression and Protease‐mediated Vimentin Degradation during Differentiation of Human Monocytic Leukemia Cells
Authors: Honke Koichi , Wada Yoshinao
Published: August 2005

Terminal differentiation of human monocytic leukemia THP‐1 cells is induced in vitro by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). We investigated the effects of TPA on the expression of vimentin during the differentiation of THP‐1 cells at both the mRNA and the protein level. On northern blotting analysis, a 2.1 kb vimentin mRNA was up‐regulated by TPA. On western blotting, small vimentin molecules with a molecular mass of approximately 40 kDa were observed in the soluble fraction and increased with TPA‐induction of cellular differentiation. Since larger, including intact, vimentin molecules were detectable at a high TPA dose, we assessed the possible existence of protease activity directed against vimentin in THP‐1 cells. With incubation of the cellular lysates of THP‐1 cells, the endogenous vimentin became increasingly smaller over time, suggesting the presence of a vimentin‐degrading protease. Phenylmethylsulfonyl fluoride inhibited this apparent protease activity against vimentin, suggesting the enzyme involved to be a serine protease. Interestingly, the protease activity was down‐regulated by TPA treatment. TPA‐treated THP‐1 cells were found to express a vimentin‐fUament network based on immunocytochemical analysis using an anti‐vimentin monoclonal antibody, V9. Taken together, these observations suggest that post‐translational mechanisms work in cooperation with transcriptional regulation to maintain the vimenti intermediate filament structure in differentiated THP‐1 cells.
Peritoneal dialysis in the management of acute renal failure in 5 dogs with leptospirosis
Authors: Beckel Nicole F. , O'Toole Therese E. , Rozanski Elizabeth A. , Labato Mary A.
Published: August 2005

Objective: To describe the use of peritoneal dialysis (PD) in the management of 5 dogs with acute renal failure (ARF) caused by leptospirosis.

Case Series Summary: All dogs were treated for leptospirosis with intravenous (IV) fluids and ampicillin prior to PD. Median age of dogs was 5 years (range 2–6 years). All dogs had positive titers for Leptospira bratislava. Median duration of PD was 4 days (range 3–16 days). PD resulted in a decrease in azotemia in all dogs. Median serum blood urea nitrogen at the start of PD was 192 mg/dL (range 140–235 mg/dL) and at the end of PD was 63 mg/dL (range 48–139 mg/dL). Median serum creatinine at the start of PD and the end was 12.8 mg/dL (range 7.7–16.9 mg/dL) and 3.4 mg/dL (range 1.4–11.1 mg/dL), respectively. Complications identified during PD included hypokalemia (n=3, 60%), hypoalbuminemia (n=2, 40%), hypomagnesemia (n=1, 20%), pelvic limb edema (n=2, 40%), central nervous system signs (n=2, 40%), dialysate retention (n=1, 20%), and leakage from the catheter site (n=1, 20%). Peritonitis was not identified in any of the dogs. Four dogs (80%) survived to discharge from the hospital. PD was effective for management of uremia in dogs with ARF caused by leptospirosis.
Effect of Alpha-Melanocyte-Stimulating Hormone on Interleukin 8 and Monocyte Chemotactic Protein 1 Expression in a Human Retinal Pigment Epithelial Cell Line
Authors: Cui Hu-Shan , Hayasaka Seiji , Zhang Xue-Yun , Chi Zai-Long , Hayasaka Yoriko
Published: August 2005

Purpose: To examine melanocortin receptor (from MC-1 to MC-5) mRNA and the effect of α-melanocyte-stimulating hormone (α-MSH) on interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) expression in a human retinal pigment epithelial cell line (ARPE-19) stimulated with IL-1β or tumor necrosis factor α (TNF-α). Methods: Expressions of MC-1 to MC-5 mRNA were examined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). α-MSH and IL-1β or TNF-α were added to serum-free medium. IL-8 and MCP-1 mRNA were measured by real-time PCR. IL-8 and MCP-1 protein concentrations were measured using enzyme-linked immunosorbent assay. Nuclear factor ĸB (NF-ĸB) translocation was examined by immunofluorescent staining/microscopy. Results: MC-1 to MC-5 receptor mRNA was expressed in unstimulated cells. IL-1β stimulated IL-8 and MCP-1 mRNA at 6 h. TNF-α stimulated IL-8 and MCP-1 mRNA expression at 1.5 and 3 h. α-MSH (10–14 to 10–10M) inhibited IL-8 and MCP-1 mRNA expression in the cells stimulated with IL-1β or TNF-α. α-MSH inhibited IL-1β or TNF-α-stimulated IL-8 and MCP-1 protein levels in the media. Immunofluorescent staining/microscopy of NF-ĸB in the nucleus was dense 30 min after stimulation with IL-1β or TNF-α and was decreased by α-MSH. Conclusions: ARPE-19 cells had MC-1 mRNA. α-MSH inhibited IL-8 and MCP-1 expression and protein secretion. Possibly, the effect on chemotactic factors may be via suppression of NF-ĸB translocation.
Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of Adult Stroke Rehabilitation Care
Authors: Bates Barbara , Choi John Y. , Duncan Pamela W. , Glasberg Jonathan J. , Graham Glenn D. , Katz Richard C. , Lamberty Kerri , Reker Dean , Zorowitz Richard
Published: August 2005

Background—

A panel of experts developed stroke rehabilitation guidelines for the Veterans Health Administration and Department of Defense Medical Systems.

Methods—

Starting from previously established guidelines, the panel evaluated published literature through 2002, using criteria developed by the US Preventive Services Task Force. Recommendations were based on evidence from randomized clinical trials, uncontrolled studies, or consensus expert opinion if definitive data were lacking.

Results—

Recommendations with Level I evidence include the delivery of poststroke care in a multidisciplinary rehabilitation setting or stroke unit, early patient assessment via the NIH Stroke Scale, early initiation of rehabilitation therapies, swallow screening testing for dysphagia, an active secondary stroke prevention program, and proactive prevention of venous thrombi. Standardized assessment tools should be used to develop a comprehensive treatment plan appropriate to each patient’s deficits and needs. Medical therapy for depression or emotional lability is strongly recommended. A speech and language pathologist should evaluate communication and related cognitive disorders and provide treatment when indicated. The patient, caregiver, and family are essential members of the rehabilitation team and should be involved in all phases of the rehabilitation process. These recommendations are available in their entirety at http://stroke.ahajournals.org/cgi/content/full/36/9/e100. Evidence tables for each of the recommendations are also in the full document.

Conclusions—

These recommendations should be equally applicable to stroke patients receiving rehabilitation in all medical system settings and are not based on clinical problems or resources unique to the Federal Medical System.
Microstructural characterisation of stir zone containing residual ferrite in friction stir welded 304 austenitic stainless steel
Authors: Park S. H. C. , Sato Y. S. , Kokawa H. , Okamoto K. , Hirano S. , Inagaki M.
Published: August 2005

Friction stir welding was applied to a 2 mm thick 304 austenitic stainless steel plate. The microstructural evolution and hardness distribution in the weld were investigated. The stir zone (SZ) and thermomechanically affected zone (TMAZ) showed dynamically recrystallised and recovered microstructures, respectively, which are typically observed in friction stir welds in aluminium alloys. The hardness of the SZ was higher than that of the base material and the maximum hardness was observed at the TMAZ. The higher hardness at the TMAZ was attributed to high densities of dislocations and subboundaries. Microstructural observations revealed that the ferrite was formed along grain boundaries of the austenite matrix in the advancing side of the SZ. It is suggested that the frictional heat due to stirring resulted in the phase transformation of austenite to ferrite and that upon rapid cooling the ferrite was retained in the SZ.
Development of circumferential TIG welding process model: A simulation model for welding of pipe and plate
Authors: Miyasaka F. , Yamane Y. , Ohji T.
Published: August 2005

It is useful to develop a numerical model for various welding positions in order to understand welding phenomena. Welding simulation models for a particular application could help in offline robot programming and online robot control. The objective of this study was to develop a tungsten inert gas (TIG) welding simulation model for various workpieces of different shapes. The present model may be easily applied to several workpiece configurations. This article deals with a model for circumferential welding of a pipe to a plate of mild steel, and aluminium alloys. The calculated results clarify that a homogeneous weld is hardly obtained at a fixed pipe welding position due to gravity, and that weld bead shape varies sensitively with wall thickness in pipe to plate welding. It is concluded that the model proposed in this article is useful to simply simulate TIG welding and provides a powerful means to estimate the optimum process parameters in welding practice.
Numerical simulation of welding-induced distortion in thin-walled structures
Authors: Dhingra A. K. , Murphy C. L.
Published: August 2005

A sequentially coupled thermal stress analysis approach is presented for modelling temperature and distortion profiles resulting from welding thin-walled structures. The material is modelled as thermo-elastic–plastic with isotropic strain hardening. The heat source is modelled as a three-dimensional (3-D) double ellipsoid, and 3-D finite element (FE) models are employed for predicting ensuing distortions. Comparisons between the simulation results and experiments performed for eight weld configurations are presented. The weld configurations include bead-on-plate, butt weld and tee joint welds with varying plate thicknesses. Temperature measurements using thermocouples and an infrared (IR) imaging radiometer are directly compared to the thermal simulations. Likewise, distortions measured directly on the experimental set-ups are compared to the FE distortion predictions. Very good correlation is obtained for temperature as well as distortion predictions between experimental and proposed numerical approaches. Lastly, details of a weld simulation for the rear section of a motorcycle frame are presented.
Integrated modelling of thermal cycles, austenite formation, grain growth and decomposition in the heat affected zone of carbon steel
Authors: Zhang W. , Elmer J. W. , DebRoy T.
Published: August 2005

The microstructure evolution in the heat affected zone (HAZ) of 1005 low carbon steel during gas tungsten arc welding (GTAW) was quantitatively investigated using a combination of several numerical models. In particular, the α ferrite→ γ austenite phase transformation during heating was studied using a Johnson–Mehl–Avrami (JMA) analysis, the γ grain growth was calculated using a Monte Carlo simulation, and the γ→ α transformation during cooling was examined using an austenite decomposition model. In addition, the phase equilibria of the 1005 steel were calculated using computational thermodynamics software, Thermo-Calc, while the necessary temperature v. time data for all the microstructure models were obtained from a thermofluid model. These models were then used to calculate the extent of austenitisation with time during heating, the γ grain growth, and the volume fractions of various microconstituents of the final microstructure in the HAZ. It was found that a considerable amount of superheat was required for the initiation and completion of the α→ γ transformation under the heating rates typical of arc welding. Significant γ grain growth was found to take place in the HAZ, particularly in the vicinity of the fusion zone (FZ) boundary, where the computed maximum γ grain size was about eight times greater than that of the base metal. The predicted final microstructure in the HAZ was predominantly allotriomorphic and Widmanstatten ferrites, which was consistent with the post-weld metallographic measurements. Overall, the computed microstructure evolution in the HAZ using the multiphenomena models was consistent with the available experimental data. The results reported here indicate that it is now possible to develop a quantitative model of complex weld microstructure evolution with the recent advances in transport phenomena and phase transformation models.
Disparities in All-Cause Mortality Beyond the Acute Phase of the COVID-19 Pandemic in the US
Authors: Berry Kaitlyn M. , Stokes Andrew C. , Morris Keeley J. , Raquib Rafeya V. , Wrigley-Field Elizabeth
Published: February 2024

This cross-sectional study examines all-cause mortality in the US between March 2018 and May 2023 by sex, race and ethnicity, metropolitan status, and region.
Human Papillomavirus Vaccination Among Young Adults Before and During the COVID-19 Pandemic
Authors: Sonawane Kalyani , Garg Ashvita , Meissner Eric G. , Damgacioglu Haluk , Hill Elizabeth , Nyitray Alan G. , Deshmukh Ashish A.
Published: February 2024

This cross-sectional survey study assesses the self-reported human papillomavirus vaccination rate by sociodemographic characteristics in adults aged 18 to 26 years from 2018 to 2022.
Establishment of immortalized Egyptian Rousettus bat cell lines
Authors: Bai Lanlan , Tani Tetsuya , Kobayashi Takeshi , Nouda Ryotaro , Kanai Yuta , Sano Yusuke , Takami Kazutoshi , Tomita Hiroshi , Sugano Eriko , Ozaki Taku , Kiyono Tohru , Fukuda Tomokazu
Published: February 2024

The Egyptian Rousettus bat (Rousettus aegyptiacus) is a common fruit bat species that is distributed mainly in Africa and the Middle East. Bats serve as reservoir hosts for numerous pathogens. Human activities, such as hunting bats for food, managing vermin, and causing habitat loss, elevate the likelihood of transmission of bat pathogens to humans and other animals. Consequently, bat cell lines play a crucial role as research materials for investigating viral pathogens. However, the inherent limitation of finite cell division in primary cells necessitates the use of immortalized cells derived from various bat tissues. Herein, we successfully established six fibroblast cell lines derived from an infant bat heart and lungs and an elderly bat heart. Three of the six cell lines, called K4DT cells, were transduced by a combination of cell cycle regulators, mutant cyclin‐dependent kinase 4, cyclin D1, and human telomerase reverse transcriptase. The other three cell lines, named SV40 cells, were transfected with simian virus 40 large T antigen. Transgene protein expression was detected in the transduced cells. All three K4DT cell lines and one lung‐derived SV40 cell line were virtually immortalized and nearly maintained the normal diploid karyotypes. However, the two other heart‐derived SV40 cell lines had aberrant karyotypes and the young bat‐derived cell line stopped proliferating at approximately 40 population doublings. These bat cell lines are valuable for studying pathogen genomics and biology.
Livestock guardian dogs establish a landscape of fear for wild predators: Implications for the role of guardian dogs in reducing human–wildlife conflict and supporting biodiversity conservation
Authors: van Bommel Linda , Magrath Michael , Coulson Graeme , Johnson Chris N.
Published: February 2024

Livestock guardian dogs (LGDs) are increasingly used to protect livestock from predators, but their effects on the distribution and behaviour of wild predators are mostly unknown. A key question is whether LGDs exclude predators from grazing land, or if predators continue to use areas with LGDs but modify their behaviour in ways that reduce impacts on livestock.

We studied effects of LGDs (Maremma sheepdogs) on distribution and behaviour of red foxes Vulpes vulpes in north‐eastern Victoria, Australia. We mapped the activity of LGDs across the study areas using GPS tracking and measured fox activity using remote cameras. We also measured risk‐sensitive foraging in foxes to test if they reduced feeding time at sites regularly used by LGDs.

Foxes occurred throughout areas occupied by LGDs, but their probability of detection was negatively related to the probability of LGD presence. Foxes extracted fewer food items from experimental food stations in proportion to the intensity of local activity of LGDs. This indicates that, though foxes overlapped with LGDs, they responded to risk of encountering LGDs by allocating less time to foraging.

While LGDs do not necessarily exclude wild predators from areas used for livestock production, they can have strong effects on predator behaviour. Reduction in time allocated to foraging in areas regularly used by LGDs could lead to suppression of hunting behaviour and therefore a reduction in attacks on livestock. The flexible response of predators to LGDs should facilitate coexistence of wild predators with livestock farming, by allowing predators to continue to use areas occupied by livestock while still preventing attacks on those livestock. Our results therefore strengthen the case for use of LGDs in the conservation of predators threatened by conflict with farming. Suppression of hunting behaviour should also mean that prey species experience reduced rates of predation on farmland with LGDs. This effect could be valuable for conservation of threatened species of prey.
AI‐ALOE: AI for reskilling, upskilling, and workforce development
Authors: Goel Ashok , Dede Chris , Garn Myk , Ou Chaohua
Published: February 2024

The National AI Institute for Adult Learning and Online Education (AI‐ALOE) develops AI learning and teaching assistants to enhance the proficiency of adult reskilling and upskilling, and thereby transform workforce development. The AI assistants both address known problems in online education for reskilling/upskilling and help personalize adult learning for workforce development. AI‐ALOE develops new AI models and techniques for self‐explanation, machine teaching, and mutual theory of mind to make the AI assistants usable, learnable, teachable, and scalable. AI‐ALOE is also developing a data architecture for deploying and evaluating the AI assistants, collecting and analyzing data, and personalizing learning at scale.
Efficacy and tolerability of adjunctive lacosamide in patients aged <4 years with focal seizures
Authors: Makedonska Iryna , Ng Yu‐Tze , Beller Cynthia , Bozorg Ali , Csikós János , McClung Carrie , Moeltgen Holger , Farkas Mark Kristof ,   the SP0967 Study Group
Published: February 2024

Objective

Primary objective was to evaluate efficacy of lacosamide administered concomitantly with 1–3 antiseizure medications in young children with uncontrolled focal (partial‐onset) seizures.

Methods

Double‐blind, parallel‐group trial (SP0967: NCT02477839/2013‐000717‐20) conducted between June 2015 and May 2020 at hospitals and clinics in 25 countries. Patients (aged ≥1 month to <4 years) with uncontrolled focal seizures were randomized 1:1 to adjunctive lacosamide or placebo using an interactive voice/web response system and stratified by age. After a 20‐day titration period, patients who reached target‐dose range (8–12 mg/kg/day) entered a 7‐day maintenance period. Region‐specific primary efficacy variables were based on ≤72‐h video‐electroencephalograms: change in average daily frequency (ADF) of electrographic focal seizures as measured on end‐of‐maintenance video‐electroencephalogram versus end‐of‐baseline video‐electroencephalogram (United States); 50% responder rate (≥50% reduction in ADF of focal seizures) during maintenance (European Union).

Results

In total, 255 patients were randomized (lacosamide/placebo: 128/127) and received ≥1 trial medication dose. Percentage reduction in ADF of focal seizures for lacosamide (116 patients) versus placebo (120 patients) was 3.2% (95% confidence interval = −13.6 to 17.5, p = 0.69). 50% responder rate was 41.4% for lacosamide (116 patients), 37.5% for placebo (120 patients) (p = 0.58). Treatment‐emergent adverse events were reported by 44.5% of lacosamide‐treated patients (placebo 51.2%).

Interpretation

Adjunctive lacosamide did not show superior efficacy versus placebo in young children with focal seizures. However, efficacy variables were potentially affected by high variability and low reliability between readers in video‐electroencephalogram interpretation. Lacosamide was generally well tolerated; safety profile was acceptable and consistent with that in adults and children aged ≥4 years.
Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder
Authors: Santoro Jonathan D. , Khoshnood Mellad M. , Jafarpour Saba , Nguyen Lina , Boyd Natalie K. , Vogel Benjamin N. , Kammeyer Ryan , Patel Lina , Manning Melanie A. , Rachubinski Angela L. , Filipink Robyn A. , Baumer Nicole T. , Santoro Stephanie L. , Franklin Catherine , Tamrazi Benita , Yeom Kristen W. , Worley Gordon , Espinosa Joaquin M. , Rafii Michael S.
Published: February 2024

Objective

To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses.

Methods

A multicenter, retrospective, case–control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10–30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities.

Results

In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p < 0.001, 95%CI: 2.18–7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) (p = 0.18, OR: 1.63, 95%CI: 0.79–3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) (p < 0.001, OR: 7.31, 95%CI: 2.83–18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p < 0.001, OR: 8.42. 95%CI: 3.78–18.76) and less likely to respond to benzodiazepines (p = 0.01, OR: 0.45, 95%CI: 0.25–0.83), antipsychotics (p < 0.001, OR: 0.28, 95%CI: 0.11–0.55), or electroconvulsive therapy (p < 0.001, OR: 0.12; 95%CI: 0.02–0.78) compared to individuals without these neuroimaging abnormalities.

Interpretation

This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy.
Coral‐Inspired Hollow Microneedle Patch with Smart Sensor Therapy for Wound Infection
Authors: Liu Yanhua , He Chaofan , Qiao Tianhong , Liu Guofeng , Li Xue , Wan Qianbing , Zhu Zhou , He Yong
Published: February 2024

Every year, over 12 million people are enduring the persistent pain resulting from wound infections. In these chronic wounds, concealed infections may be covered up by scabs or granulation, which impeding accurate diagnosis and treatment. To address such clinical challenges, inspired by corals, a biomimetic microneedle patch (HepMi‐PCL) is developed to indicate and treat infections within wound. Relying on high‐precision 3D printing technology, each polycaprolactone microneedle own an equally sized porous shell and cavity with heparin‐based functional hydrogel filling in. After penetrating through the scab, HepMi‐PCL can absorb exudate in wound through surficial guide grooves and pores microstructure on its microneedle, thereby indicating whether anti‐infection is needed. Upon the identification of a positive chronic infection, HepMi‐PCL will smartly activate to release drugs rapidly. Subsequently, when the infection is effectively managed and the exudate progressively decreases, the drug delivery will correspondingly slow down or cease altogether. By leveraging autonomous response and therapeutic capabilities, HepMi‐PCL demonstrates the potential to expedite the diagnosis and treatment of infections, resulting in an enhancement of healing speed for infected wounds by over 200%. Thus, the integration of diagnostic and therapeutic functions of the microneedle patch is anticipated to offer novel approaches in addressing the management of chronic wounds.
Spiders Use Structural Conversion of Globular Amyloidogenic Domains to Make Strong Silk Fibers
Authors: Qi Xingmei , Wang Han , Wang Kezhen , Wang Yu , Leppert Axel , Iashchishyn Igor , Zhong Xueying , Zhou Yizhong , Liu Ruifang , Rising Anna , Landreh Michael , Johansson Jan , Chen Gefei
Published: February 2024

Spider silk—an environmentally friendly protein‐based material—is widely recognized for its extraordinary mechanical properties. Biomimetic spider silk‐like fibers made from recombinant spider silk proteins (spidroins) currently falls short compared to natural silks in terms of mechanical performance. In this study, it is discovered that spiders use structural conversion of molecular enhancers—conserved globular 127‐residue spacer domains—to make strong silk fibers. This domain lacks poly‐Ala motifs but interestingly contains motifs that are similar to human amyloidogenic motifs, and that it self‐assembles into amyloid‐like fibrils through a non‐nucleation‐dependent pathway, likely to avoid the formation of cytotoxic intermediates. Incorporating this spacer domain into a recombinant chimeric spidroin facilitates self‐assembly into silk‐like fibers, increases fiber molecular homogeneity, and markedly enhances fiber mechanical strength. These findings highlight that spiders employ diverse strategies to produce silk with exceptional mechanical properties. The spacer domain offers a way to enhance the properties of recombinant spider silk‐like fibers and other functional materials.
Focusing Micromechanical Polaritons in Topologically Nontrivial Hyperbolic Metasurfaces
Authors: Zheng Jiang‐Po , Zheng Li‐Yang , Yu Si‐Yuan , Yang Shi‐Li , Sun Xiao‐Chen , Liu Le , Lu Ming‐Hui , Chen Yan‐Feng , Christensen Johan
Published: February 2024

Vertically stacked multiple atomically thin layers have recently widened the landscape of rich optical structures thanks to these quantum metamaterials or van der Waals (vdW) materials, featuring hyperbolic polaritons with unprecedented avenues for light. Despite their far‐reaching implications, most of their properties rest entirely on a trivial band topological origin. Here, a 2D approach is adopted toward a micromechanical vdW analogue that, as a result of engineered chiral and mirror symmetries, provides topologically resilient hyperbolic radiation of mechanical vibrations in the ultrasonic regime. By applying laser vibrometry of the micrometer‐sized metasurface, we are able to exhibit the exotic fingerprints of robust hyperbolic radiation spanning several frequencies, which beyond their physical relevance, may enable ultrasonic technologies.
Stainless Steel Activation for Efficient Alkaline Oxygen Evolution in Advanced Electrolyzers
Authors: Zuo Yong , Mastronardi Valentina , Gamberini Agnese , Zappia Marilena I. , Le Thi‐Hong‐Hanh , Prato Mirko , Dante Silvia , Bellani Sebastiano , Manna Liberato
Published: February 2024

Designing robust and cost‐effective electrocatalysts for efficient alkaline oxygen evolution reaction (OER) is of great significance in the field of water electrolysis. In this study, an electrochemical strategy to activate stainless steel (SS) electrodes for efficient OER is introduced. By cycling the SS electrode within a potential window that encompasses the Fe(II)↔Fe(III) process, its OER activity can be enhanced to a great extent compared to using a potential window that excludes this redox reaction, decreasing the overpotential at current density of 100 mA cm−2 by 40 mV. Electrochemical characterization, Inductively Coupled Plasma – Optical Emission Spectroscopy, and operando Raman measurements demonstrate that the Fe leaching at the SS surface can be accelerated through a Fe → γ‐Fe2O3 → Fe3O4 or FeO → Fe2+ (aq.) conversion process, leading to the sustained exposure of Cr and Ni species. While Cr leaching occurs during its oxidation process, Ni species display higher resistance to leaching and gradually accumulate on the SS surface in the form of OER‐active Fe‐incorporated NiOOH species. Furthermore, a potential‐pulse strategy is also introduced to regenerate the OER‐activity of 316‐type SS for stable OER, both in the three‐electrode configuration (without performance decay after 300 h at 350 mA cm−2) and in an alkaline water electrolyzer (≈30 mV cell voltage increase after accelerated stress test‐AST). The AST‐stabilized cell can still reach 1000 and 4000 mA cm−2 at cell voltages of 1.69 and 2.1 V, which makes it competitive with state‐of‐the‐art electrolyzers based on ion‐exchange membrane using Ir‐based anodes.
Ferroelectric 2D SnS2 Analog Synaptic FET
Authors: Song Chong‐Myeong , Kim Dongha , Lee Shinbuhm , Kwon Hyuk‐Jun
Published: February 2024

In this study, the development and characterization of 2D ferroelectric field‐effect transistor (2D FeFET) devices are presented, utilizing nanoscale ferroelectric HfZrO2 (HZO) and 2D semiconductors. The fabricated device demonstrated multi‐level data storage capabilities. It successfully emulated essential biological characteristics, including excitatory/inhibitory postsynaptic currents (EPSC/IPSC), Pair‐Pulse Facilitation (PPF), and Spike‐Timing Dependent Plasticity (STDP). Extensive endurance tests ensured robust stability (107 switching cycles, 105 s (extrapolated to 10 years)), excellent linearity, and high Gmax/Gmin ratio (>105), all of which are essential for realizing multi‐level data states (>7‐bit operation). Beyond mimicking synaptic functionalities, the device achieved a pattern recognition accuracy of ≈94% on the Modified National Institute of Standards and Technology (MNIST) handwritten dataset when incorporated into a neural network, demonstrating its potential as an effective component in neuromorphic systems. The successful implementation of the 2D FeFET device paves the way for the development of high‐efficiency, ultralow‐power neuromorphic hardware which is in sub‐femtojoule (48 aJ/spike) and fast response (1 µs), which is 104 folds faster than human synapse (≈10 ms). The results of the research underline the potential of nanoscale ferroelectric and 2D materials in building the next generation of artificial intelligence technologies.
Regulating the Quantum Dots Integration to Improve the Performance of Tin–Lead Perovskite Solar Cells
Authors: Mubarok Muhibullah Al , Kim Yu Jin , Imran Imil Fadli , Hwang Jin‐Ha , Lee Sang‐Hak , Seog Hae Jin , Kwak Sang Kyu , Jang Sung‐Yeon
Published: February 2024

Despite their advantageous attributes, such as a narrow bandgap and reduced toxicity, tin–lead halide perovskites (TLHPs) have received limited attention due to their lower power conversion efficiency (PCE) relative to lead‐only variants. In this study, a transformative approach is introduced that leverages perovskite quantum dots (PQDs) to optimize TLHP solar cells. While conventional oleyl‐capped PQDs enhance the open circuit voltage (VOC), the long‐chain ligands hinder charge transport. To overcome this limitation, a post‐treatment with isopropyl alcohol effectively dissociates these ligands and PQD crystals, resulting in reduced defect density, improved charge transfer, and elevated quasi‐Fermi level splitting in the TLHP device. Consequently, the PCE of the device is notably increased from 19.0% to 23.74% and elevated the VOC from 0.78 to 0.87 V, without compromising the photocurrent or fill factor. The findings highlight PQD modification as a compelling avenue for TLHP solar cell enhancement, particularly in boosting VOC.
Salivary biomarkers: The early diagnosis of Alzheimer's disease
Authors: Nazir Sophia
Published: February 2024

The precise identification of Alzheimer's disease and other prevalent neurodegenerative diseases remains a difficult issue that requires the development of early detection of the disease and inexpensive biomarkers that can replace the present cerebrospinal fluid and imaging biomarkers. Blood biomarkers, such as amyloid and neurofilament light, have been emphasized as an important and practical tool in a testing or examination procedure thanks to advancements in ultra‐sensitive detection techniques. Although saliva is not currently being researched for neurodegenerative diseases, it is an important source of biomarkers that can be used for the identification of diseases and has some advantages over other biofluids. While this may be true for most people, getting saliva from elderly people presents some significant challenges. In this overview, we will first discuss how saliva is created and how aging‐related illnesses may affect the amount and kind of saliva produced. The findings support the use of salivary amyloid protein, tau species, and novel biomarkers in the diagnosis of Alzheimer's disease.
Disentangling differing relationships between internalizing disorders and alcohol use
Authors: Brasher Maizy S. , Grotzinger Andrew D. , Friedman Naomi P. , Smolker Harry R. , Evans Luke M.
Published: February 2024

Both internalizing disorders and alcohol use have dramatic, wide‐spread implications for global health. Previous work has established common phenotypic comorbidity among these disorders, as well as shared genetic variation underlying them both. We used genomic structural equation modeling to investigate the shared genetics of internalizing, externalizing, and alcohol use traits, as well as to explore whether specific domains of internalizing symptoms mediate the contrasting relationships with problematic alcohol use compared to alcohol consumption. We also examined patterns of genetic correlations between similar traits within additional Finnish and East Asian ancestry groups. When the shared genetic influence of externalizing psychopathology was accounted for, the genetic effect of internalizing traits on alcohol use was reduced, suggesting the important role of common genetic factors underlying multiple psychiatric disorders and their genetic influences on comorbidity of internalizing and alcohol use traits. Individual internalizing domains had contrasting effects on frequency of alcohol consumption, which demonstrate the complex system of pleiotropy that exists, even within similar disorders, and can be missed when evaluating only relationships among formal diagnoses. Future work must consider the broad effects of shared psychopathology along with the fine‐scale effects of heterogeneity within disorders to more fully understand the biology underlying complex traits.
Intergenerational financial assistance with home ownership: Considering the potential for financial elder abuse
Authors: Cook Julia , Cook Peta S.
Published: February 2024

Intergenerational financial assistance with home ownership has attracted increasing scholarly interest in recent years. Existing research has focussed primarily on its impact on inequality, housing market outcomes and notions of meritocracy, as well as the relational dynamics through which it is negotiated. The topic of financial elder abuse has, however, remained an area of relative silence in this literature despite concerns raised by advocacy groups. In this article, we consider how intergenerational financial assistance may facilitate attitudes and behaviours that can result in financial elder abuse. To do so, we draw on an analysis of the Banking Code of Practice and the presumption of advancement, each of which shapes the way intergenerational financial assistance with home ownership unfolds in Australia. We then consider how such arrangements play out in practice through analysis of interviews conducted with donors and recipients of assistance of this type. We ultimately argue that in the context of intergenerational financial assistance with home ownership, the potential for financial elder abuse should be considered not just as an individual or family issue rooted in relationships, but as the outcome of ageist social attitudes and structural problems in the asset economy.
Protective effect of bilingualism on aging, MCI, and dementia: A community‐based study
Authors: Venugopal Aparna , Paplikar Avanthi , Varghese Feba Anna , Thanissery Nithin , Ballal Divya , Hoskeri Rakshith Maneshwar , Shekar Revathi , Bhaskarapillai Binukumar , Arshad Faheem , Purushothaman Vandana Valiyaparambath , Anniappan Aravind Banavaram , Rao Girish Nagaraja , Alladi Suvarna
Published: February 2024

INTRODUCTION

Lifelong bilingualism is associated with a delayed age at onset of dementia, but evidence from community‐based studies is limited. We investigated the relationship between bilingualism and the prevalence of cognitive impairment in a linguistically diverse community.

METHODS

A door‐to‐door community study was conducted from January to December 2021 in urban Bengaluru, India. 1234 individuals aged ≥60 years participated in the study. Participants were diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), or dementia using established diagnostic criteria.

RESULTS

Dementia prevalence was higher in monolinguals (4.9%) than bilinguals (0.4%) (P = .001). The prevalence of MCI was also higher in monolinguals (8.5%) than bilinguals (5.3%) (P = .001). The study also revealed better cognitive function in bilinguals than monolinguals with NCI, after controlling for confounding variables.

DISCUSSION

The current study provides significant support for the protective effect of bilingualism on cognitive impairment in an urban community with extensive bilingual interactional contexts in everyday life.

Highlights

Bilingualism has been demonstrated to protect against dementia and mild cognitive impairment in a linguistically diverse community with extensive code‐switching contexts.

Bilingual older individuals had superior baseline cognitive performance compared to monolingual older individuals.

Bilingualism was found to have an independent effect on general cognition after adjusting for major social determinants of health in the group without cognitive impairment.