bluuebunny/crossref_metadata_2025 huggingface dataset:
National Institutes of Health Funding Gaps for Principal Investigators
Authors: Gillen Kelly M. , Markowitz Daniel M. , Long Patricia , Villegas-Estrada Adriel , Chang Eileen , Gupta Ajay
Published: September 2023

Importance

Early-stage and established investigators compete for a limited supply of funds from the National Institutes of Health (NIH). Regardless of their previous funding success, many principal investigators (PIs) encounter a funding gap in which they no longer receive ongoing funding from the NIH.

Objective

To determine incidence rates of PI-level funding gaps, the mean funding gap length, and whether these 2 metrics are associated with previous funding success.

Design, Setting, and Participants

This study was conducted using data from NIH RePORTER. Historical datafiles for fiscal year (FY) 2011 to FY 2021 were aggregated to generate 2 master datafiles for this period: all NIH awards and only R01 awards. PIs with no funding in FY 2011 or FY 2021 were removed. PIs were sorted by FY 2011 total funding amounts and grouped by quarter of amount.

Results

A total of 39 944 unique researchers were awarded 220 131 NIH awards, of which 103 753 were R01 awards. For all NIH awards, there was an overall linear increase from top quarter to bottom quarter in the percentage of PIs who had at least 1 year without funding (from 27% to 75%), percentage of these gap PIs who had at least 2 consecutive years without funding (from 56% to 68%), and mean maximum consecutive years without funding for gap PIs (2.2 years to 3.1 years). For only R01 awards, there was an overall linear increase from top quarter to bottom quarter in the percentage of PIs who had at least 1 year without funding (50% to 74%), percentage of gap PIs who had at least 2 consecutive years without funding (59% to 71%), and mean maximum consecutive years without funding for gap PIs (2.4 years to 3.1 years).

Conclusions and Relevance

In this cohort study of NIH-funded investigators, PIs with higher NIH funding were less likely to experience a funding gap. Additionally, when these PIs encountered a funding gap, this period without funding was shorter; however, among all PIs, funding gaps typically lasted 2 to 3 years. These associations were found inclusive of all NIH awards and when analysis was limited to only R01 awards. These findings may be useful to PIs and academic institutions as they prepare, structure, and project research resource allocations.
Skilled Nursing Facility Changes in Ownership and Short-Stay Medicare Patient Outcomes
Authors: Prusynski Rachel A. , Humbert Andrew , Mroz Tracy M.
Published: September 2023

Importance

Skilled nursing facility (SNF) changes in ownership are receiving attention in the national conversation regarding health care quality and oversight. SNF ownership changes have been cited as possible ways for SNFs to obscure financial arrangements and shift funds away from patient care; however, it is unclear whether ownership changes are associated with quality outcomes, especially for short-stay patients.

Objective

To determine which SNF characteristics are associated with changes in ownership and whether ownership changes were associated with differences in short-stay patient outcomes.

Design, Setting, and Participants

This cohort study was a secondary analysis of 2016 to 2019 Medicare administrative data including SNFs in the United States with complete data. Data were analyzed from January 2016 through December 2019.

Exposure

SNF change in ownership.

Main Outcomes and Measures

Outcomes of interest were facility-level risk-adjusted rates of hospital readmissions, emergency department visits, and community discharge for short-stay patients after admission to an SNF. Analyses were conducted using multivariable logistic regression and controlled interrupted time series.

Results

Of 11 004 SNFs, 1459 (13.26%) changed ownership between 2016 and 2019. Compared with for-profit SNFs, nonprofit and government SNFs had lower odds of changing ownership (nonprofit: odds ratio [OR], 0.40; 95% CI, 0.32-0.49; government: OR, 0.26; 95% CI, 0.17-0.41). Chain SNFs had higher odds of changing ownership than nonchain SNFs (OR, 1.38; 95% CI, 1.21-1.59). Urban SNFs with lower occupancy rates (OR per 10–percentage-point decrease, 1.19; 95% CI, 1.14-1.25), larger Medicaid populations (OR per 10–percentage-point increase, 1.17; 95% CI, 1.13-1.22), and lower staffing ratings (OR per 1-star increase on staffing rating, 1.18; 95% CI, 1.14-1.25) had higher odds of changing ownership. Descriptively, all 3 quality outcomes were worse throughout the study in SNFs undergoing ownership change compared with controls that did not change ownership. However, results of interrupted time series models found no associations between an ownership change and hospital readmissions or community discharge rates. Ownership change was associated with a short-term increase of 0.32 (95% CI, 0.03 to 0.62) percentage points in emergency department visits.

Conclusions and Relevance

In this cohort study of 11 004 SNFs in the US between 2016 and 2019, SNF characteristics historically associated with lower quality were more likely to change ownership; however, ownership changes were only associated with short-term increases in ED visits. These results suggest that SNF ownership changes may be a symptom, not a cause, of lower quality.
Viability of the virtual cone technique using a fixed small multi‐leaf collimator field for stereotactic radiosurgery of trigeminal neuralgia
Authors: Neupane Taindra , Shang Charles , Kassel Maxwell , Muhammad Wazir , Leventouri Theodora , Williams Timothy R.
Published: September 2023

Dosimetric uncertainties in very small (≤1.5 × 1.5 cm2) photon fields are remarkably higher, which undermines the validity of the virtual cone (VC) technique with a diminutive and variable MLC fields. We evaluate the accuracy and reproducibility of the VC method with a very small, fixed MLC field setting, called a fixed virtual cone (fVC), for small target radiosurgery such as trigeminal neuralgia (TGN). The fVC is characterized by 0.5 cm x 0.5 cm high‐definition (HD) MLC field of 10MV FFF beam defined at 100 cm SAD, while backup jaws are positioned at 1.5 cm x 1.5 cm. A spherical dose distribution equivalent to 5 mm (diameter) physical cone was generated using 10–14 non‐coplanar, partial arcs. Dosimetric accuracy was validated using SRS diode (PTW 60018), SRS MapCHECK (SNC) measurements. As a quality assurance measure, 10 treatment plans (SRS) for TGN, consisting of various arc ranges at different collimator angles were analyzed using 6 MV FFF and 10 MV FFF beams, including a field‐by‐field study (n = 130 fields). Dose outputs were compared between the Eclipse TPS and measurements (SRS MapCHECK). Moreover, dosimetric changes in the field defining fVC, prompted by a minute (± 0.5–1.0 mm) leaf shift, was examined among TPS, diode measurements, and Monte Carlo (MC) simulations. The beam model for fVC was validated (≤3% difference) using SRS MapCHECK based absolute dose measurements. The equivalent diameters of the 50% isodose distribution were found comparable to that of a 5 mm cone. Additionally, the comparison of field output factors, dose per MU between the TPS and SRS diode measurements using the fVC field, including ± 1 mm leaf shift, yielded average discrepancies within 5.5% and 3.5% for 6 MV FFF and 10 MV FFF beams, respectively. Overall, the fVC method is a credible alternative to the physical cone (5 mm) that can be applied in routine radiosurgical treatment of TGN.
Dosimetric impact of MLC positional errors on dose distribution in IMRT
Authors: Enomoto Hiromi , Fujita Yukio , Matsumoto Saki , Nakajima Yujiro , Nagai Miyuki , Tonari Ayako , Ebara Takeshi
Published: September 2023

Optimizing the positional accuracy of multileaf collimators (MLC) for radiotherapy is important for dose accuracy and for reducing doses delivered to normal tissues. This study investigates dose sensitivity variations and complexity metrics of MLC positional error in volumetric modulated arc therapy and determines the acceptable ranges of MLC positional accuracy in several clinical situations. Treatment plans were generated for four treatment sites (prostate cancer, lung cancer, spinal, and brain metastases) using different treatment planning systems (TPSs) and fraction sizes. Each treatment plan introduced 0.25–2.0 mm systematic or random MLC leaf bank errors. The generalized equivalent uniform dose (gEUD) sensitivity and complexity metrics (MU/Gy and plan irregularity) were calculated, and the correlation coefficients were assessed. Furthermore, the required tolerances for MLC positional accuracy control were calculated. The gEUD sensitivity showed the highest dependence of systematic positional error on the treatment site, followed by TPS and fraction size. The gEUD sensitivities were 6.7, 4.5, 2.5, and 1.7%/mm for Monaco and 8.9, 6.2, 3.4, and 2.3%/mm (spinal metastasis, lung cancer, prostate cancer, and brain metastasis, respectively) for RayStation. The gEUD sensitivity was strongly correlated with the complexity metrics (r = 0.88–0.93). The minimum allowable positional error for MLC was 0.63, 0.34, 1.02, and 0.28 mm (prostate, lung, brain, and spinal metastasis, respectively). The acceptable range of MLC positional accuracy depends on the treatment site, and an appropriate tolerance should be set for each treatment site with reference to the complexity metric. It is expected to enable easier and more detailed MLC positional accuracy control than before by reducing dose errors to patients at the treatment planning stage and by controlling MLC quality based on complexity metrics, such as MU/Gy.
NIR‐II Regulation of Mitochondrial Potassium Channel with Dual‐Targeted Conjugated Oligomer Nanoparticles for Efficient Cancer Theranostics In Vivo
Authors: Li Chaoqun , Gao Dong , Gao Yijian , Zhang Ran , Qu Xiongwei , Li Shengliang , Xing Chengfen
Published: September 2023

Cell fate can be efficiently modulated by switching ion channels. However, the precise regulation of ion channels in cells, especially in specific organelles, remains challenging. Herein, biomimetic second near‐infrared (NIR‐II) responsive conjugated oligomer nanoparticles with dual‐targeted properties are designed and prepared to modulate the ion channels of mitochondria to selectively kill malignant cells in vivo. Upon 1060 nm laser irradiation, the mitochondria‐located nanoparticles photothermally release a specific ion inhibitor of the potassium channel via a temperature‐sensitive liposome, thus altering the redox balance and pathways of mitochondria. NIR‐II responsive nanoparticles can effectively regulate the potassium channels of mitochondria and fully suppress tumor growth. This work provides a new modality based on the NIR‐II nanoplatform to regulate ion channels in specific organelles and proposes an effective therapeutic mechanism for malignant tumors.
Covert Scattering Control in Metamaterials with Non‐Locally Encoded Hidden Symmetry
Authors: Sol Jérôme , Röntgen Malte , del Hougne Philipp
Published: September 2023

Symmetries and tunability are of fundamental importance in wave scattering control, but symmetries are often obvious upon visual inspection, which constitutes a significant vulnerability of metamaterial wave devices to reverse‐engineering risks. Here, it is theoretically and experimentally shown that a symmetry in the reduced basis of the “primary meta‐atoms” that are directly connected to the outside world is sufficient; meanwhile, a suitable topology of non‐local interactions between them, mediated by the internal “secondary” meta‐atoms, can hide the symmetry from sight in the canonical basis. Covert symmetry‐based scattering control in a cable‐network metamaterial featuring a hidden parity () symmetry in combination with hidden‐‐symmetry‐preserving and hidden‐‐symmetry‐breaking tuning mechanisms is experimentally demonstrated. Physical‐layer security in wired communications is achieved using the domain‐wise hidden ‐symmetry as a shared secret between the sender and the legitimate receiver. Within the approximation of negligible absorption, the first tuning of a complex scattering metamaterial without mirror symmetry to feature exceptional points (EPs) of ‐symmetric reflectionless states, as well as quasi‐bound states in the continuum, is reported. These results are reproduced in metamaterials involving non‐reciprocal interactions between meta‐atoms, including the first observation of reflectionless EPs in a non‐reciprocal system.
Optimized V‐Doped Defective TiO2/α‐(Fe2O3)1‐x(Cr2O3)x Heterojunctions for Photo‐Assisted Supercapacitor Devices: Insights on the Materials Integrity and Dual Conversion‐Storage Mechanism
Authors: Sayed Doha M. , Bahnasawy Nour , Allam Nageh K.
Published: September 2023

Energy conversion and storage integrated power units suffer from multiple engineering issues. Replacing two devices (solar cell and supercapacitor assembly) with one device (photo‐enhanced supercapacitor‐ PSC) requires materials with emerged dual solar‐electrochemical storage attributes. Herein, a propitious approach is developed to fabricate all visible light‐enhanced semisolid flexible PCS. Nanoflakes‐based p‐n junction α‐(Fe2O3)1‐x(Cr2O3)x photocathode is synthesized directly on industrial waste stainless steel mesh (316L‐SS). Alongside, three TiO2‐based electrodes are utilized as positive photoactive electrodes. Tuning the optical properties of TiO2 is displayed via doping with mixed valence vanadium (V4+/V5+) together with thermal hydrogen annealing. This is revealed via the reduction of the bandgap energy from 2.89 to 2.15 eV, which can be ascribed to the induced oxygen vacancies. The device can sustain up to 1.6 V potential window with 91% stability after 350 successive charge/discharge cycles with the possibility of performance regeneration to its 100% retention. An illustration of the photo‐storage mechanism is proposed based on the X–ray photoelectron spectroscopy, X–ray crystallography, and band position/alignment results. Quasi‐reversible water splitting/formation is concluded as the main storage mechanism in the semisolid state electrolyte under illumination conditions.
An unusually robust specimen attributed to Buriolestes schultzi (Dinosauria: Sauropodomorpha) from the Late Triassic of southern Brazil
Authors: Moro Débora , Damke Lísie Vitória Soares , Müller Rodrigo Temp , Kerber Leonardo , Pretto Flávio Augusto
Published: September 2023

Buriolestes schultzi is a small sauropodomorph dinosaur from Carnian beds (ca., 233 Ma) of southern Brazil. It is one of the earliest members of that lineage and is a key taxon to investigate the initial evolution of Sauropodomorpha. Here, we attribute a new specimen to B. schultzi from Late Triassic of southern Brazil, which represents the first occurrence of the taxon outside the type locality. The new specimen comprises a disarticulated and partial skeleton, including cranial and postcranial elements. It is tentatively regarded as an additional specimen of B. schultzi according to a unique combination of traits (including autapomorphies). Conversely, the new specimen is stouter than the other specimens of B. schultzi, as shown by femoral Robustness Index. Based on femoral circumference, the estimated body mass of the new specimen is approximately 15 kg, which is far higher than the previous estimations for other specimens of B. schultzi (i.e., approximately 7 kg). In fact, the new specimen and some specimens of Eoraptor lunensis and Saturnalia tupiniquim were found to be significantly stouter than coeval sauropodomorphs. Therefore, instead of all being constructed as gracile, the earliest sauropodomorphs experienced an unappreciated intraspecific variation in robustness. This is interesting because more precise data on species body mass are crucial in order to better understand the complex terrestrial ecosystems in which dinosaurs originated.
Detector system challenges of the wide‐field spectroscopic survey telescope (WST)
Authors: Bacon Roland , Roth Martin M. , Amico Paola , Hernandez Eloy ,   The WST Consortium
Published: September 2023

The wide‐field spectroscopic survey telescope (WST) is proposed to become the next large optical/near infrared facility for the European southern observatory (ESO) once the extremely large telescope (ELT) has become operational. While the latter is optimized for unprecedented sensitivity and adaptive‐optics assisted image quality over a small field of view, WST addresses the need for large survey volumes in spectroscopy with the light‐collecting power of a 10‐m class telescope. Its unique layout will feature the combination of multi‐object and integral field spectroscopy simultaneously. For the intended capacity of this layout, a very large number of detectors are needed. The complexity of the detector systems presents a number of challenges that are discussed with a focus on novel approaches and innovative detector designs that can be expected to emerge over the anticipated 20‐year timeline of this project.
Simultaneous detection of SO2 and viscosity in drug‐induced inflammation in live cells and zebrafish
Authors: Kafuti Yves S. , Liu Xiaosheng , Zeng Shuang , Han Jingjing , Li Haidong , Wang Jingyun
Published: September 2023

The viscosity within cells is a crucial microenvironmental factor, and sulfur dioxide (SO2) has essential functions in regulating cellular apoptosis and inflammation. Some evidence has been confirmed that changes in viscosity and overexposure of SO2 within the cell may cause detrimental effects including, but not limited to, respiratory and cardiovascular illnesses, inflammation, fatty liver, and various types of cancer. Therefore, precise monitoring of SO2 and viscosity in biological entities holds immense practical importance. Therefore, in this research, we developed a versatile fluorescent TCF‐Cou that enables the dual detection of SO2 and viscosity in the living system. Probe TCF‐Cou possessed a response to viscosity and SO2 through red and green emissions. The alteration of SO2 and viscosity levels in live cells and zebrafish were also monitored using probe TCF‐Cou. We hope that this fluorescent probe could be a potential tool for revealing the related pathological and physiological processes through monitoring the changes in SO2 and viscosity.
LC–MS/MS methods for determination of venetoclax in human plasma and cerebrospinal fluid
Authors: Yang Yan‐Ling , Qian Zhou‐Yi , Zhao Yang , Chen Xiang‐Long , Huang Qiong‐Ye , Guo Yu‐Jiao , Sun Lu‐Ning , Wang Yong‐Qing
Published: September 2023

We developed and validated sensitive MS/MS methods for the determination of venetoclax, an oral selective B‐cell lymphoma‐2 inhibitor, in human plasma and cerebrospinal fluid (CSF). Acetonitrile was used as protein precipitant. The mobile phase was 10 mM ammonium formate consisting of 0.1% formic acid and acetonitrile (40:60, v/v). The analytes were separated on an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 μm) in 5 min. An API 4000 mass spectrometer was selected to quantify venetoclax and internal standard using m/z 868.3 → 636.3 and 876.3 → 644.3 under multiple response monitoring mode. In plasma, the calibration curve exhibited good linearity ranging from 20.0 to 5000 ng/mL, whereas in the CSF, the linear range was 0.500–100 ng/mL. The matrix effect of venetoclax and internal standard (venetoclax‐d8) was not obvious in both plasma and CSF. The inter‐ and intra‐run accuracy was within ±11.9%, and the inter‐ and intra‐run precision was below 13.6%. Both methods had no carryover, and the recovery was close to 100%. The validated methods were employed to quantify the concentrations of venetoclax in the plasma and CSF of patients diagnosed with chronic lymphocytic leukemia or acute myelogenous leukemia.
Leukoplakia of the Marginal Gingiva: A Report of Two Cases
Authors: Tosios Konstantinos I. , Vasilas Athanasios , Melakopoulos Ioannis , Sklavounou‐Andrikopoulou Alexandra
Published: September 2023

Introduction

Leukoplakia of the marginal gingivae is uncommon and in most cases reported up to date represents a manifestation of proliferative verrucous leukoplakia. The clinical and pathologic features of two cases of leukoplakia confined to the marginal gingiva are described and their biologic significance is discussed.

Case Presentation

The cases involved two female patients, non‐smokers, aged 82 and 57. The lesions clinically appeared as small, well‐demarcated white plaques on the marginal gingiva of posterior teeth. After being totally excised, microscopic examination showed keratosis of unknown significance in the first patient and verrucous hyperplasia in the latter, while immunohistochemistry for p16INK4A was negative for both. There was no recurrence in 7 months and 5 months after excision, respectively.

Conclusion

A white plaque on the marginal gingiva may be overlooked due to its small size or may be misdiagnosed as frictional keratosis. However, it may represent leukoplakia, a potentially malignant disorder. Therefore, diagnosis and management should follow the established guidelines for leukoplakia.
The Modified Apically Repositioned Flap Technique and Its Potential to Regain Gingival Melanin Pigmentation
Authors: Carnio João , Camargo Paulo M. , Chen Julia W. , Leung Ho‐Yin , Pirih Flavia Q.
Published: September 2023

Introduction

Patients that have gingival melanin pigmentation present an esthetic challenge to clinicians because it is often hard to maintain or regain this pigmentation after surgery. These cases show the Modified Apically Repositioned Flap (MARF) technique and its potential to increase the likelihood of repigmentation of the surgical site with better matching esthetic results.

Case Series

A total of six healthy, non‐smoking patients presented with the need for increased dimension of attached gingiva. All patients had pre‐existing physiologic gingival melanin pigmentation and underwent the MARF technique. Ten teeth were included in the case series and the observational follow‐up period ranged from 1 to 2 years. The surgical areas were analyzed in relation to the width of keratinized and attached gingiva, marginal tissue recession, and probing depth. The final esthetic results, were judged by 20 periodontists using standardized photographs and a grading scale from 0 to 2.

Conclusions

Treatment with MARF resulted in a significant increase in the apico‐coronal dimension of the keratinized and attached gingiva (P < 0.05). The increase in keratinized tissue ranged from 1.85 to 4.65 mm, and the increase in attached gingiva ranged from 0.8 to 3.55 mm. Probing depths and recession did not change significantly compared to initial values. Experienced clinicians judged the final esthetic results to be completely matched, with pigmentation in the healed tissue blending well with pre‐existing pigmentation.

The MARF technique should be considered as an alternative surgical technique when an increase in the apico‐coronal dimension of attached gingiva is required in patients with gingival melanin pigmentation.
Castleman disease presenting as lymphadenopathy in a female with systemic lupus erythematosus: A rare case report
Authors: Khabbazi Alireza , Khalaji Amirreza , Pourbagherian Omid , Vahedi Amir , Jafarpour Mehdi
Published: September 2023

Key Clinical Message

Castleman disease is an infrequent disease that affects the lymph nodes and related tissues. The condition may manifest with lymphadenopathy, characterized by the enlargement of the lymph nodes, alongside additional symptoms such as high fever, nocturnal sweating, exhaustion, and loss of body mass. The diagnosis of Castleman disease typically entails a multifaceted approach that includes a physical examination, imaging modalities, and a biopsy of the lymph nodes that are affected. The selection of treatment modalities is contingent upon the classification and extent of the disease. Systemic lupus erythematosus (SLE) has been identified as a potential risk factor for the development of lymphoma, a condition that may manifest with lymphadenopathy resembling Castleman disease. Hence, it is crucial for individuals diagnosed with SLE and exhibiting lymphadenopathy to undergo a comprehensive assessment to exclude the possibility of any other associated disease. Although lymphadenopathy is a common symptom shared by both Castleman illness and SLE, these diseases have distinct etiologies and are treated in different ways. Seeking advice from a healthcare practitioner is crucial in order to obtain an accurate diagnosis and effective treatment. A 39‐year‐old female patient with a history of SLE since 18 years ago and lupus nephritis since 6 years ago which treated with Mycophenolic Acid 2 g daily, Hydroxychloroquine 400 mg daily, and low doses of Prednisolone. Also, Mycophenolic Acid has discontinued for her 5 months ago due to the reduction of proteinuria and the control of the disease. Although the association of Castleman Disease with SLE is infrequent, establishing a connection between them could prove advantageous in the treatment and etiology of diseases.
Encapsulation in Charged Droplets Generates Distorted Host‐Guest Complexes**
Authors: Stares Daniel L. , Szumna Agnieszka , Schalley Christoph A.
Published: September 2023

The ability of various hydrogen‐bonded resorcinarene‐based capsules to bind α,ω‐alkylbisDABCOnium (DnD) guests of different lengths was investigated in solution and in the gas‐phase. While no host‐guest interactions were detected in solution, encapsulation could be achieved in the charged droplets formed during electrospray ionisation (ESI). This included guests, which are far too long in their most stable conformation to fit inside the cavity of the capsules. A combination of three mass spectrometric techniques, namely, collision‐induced dissociation, hydrogen/deuterium exchange, and ion‐mobility mass spectrometry, together with computational modelling allow us to determine the binding mode of the DnD guests inside the cavity of the capsules. Significant distortions of the guest into horseshoe‐like arrangements are required to optimise cation‐π interactions with the host, which also adopt distorted geometries with partially open hydrogen‐bonding seams when binding longer guests. Such quasi “spring‐loaded” capsules can form in the charged droplets during the ESI process as there is no competition between guest encapsulation and ion pair formation with the counterions that preclude encapsulation in solution. The encapsulation complexes are sufficiently stable in the gas‐phase – even when strained – because non‐covalent interactions significantly strengthen in the absence of solvent.
A GHz‐level memristor emulator with only MOSFET
Authors: Zhou Lei , Wang Chune , Chen Xiaozhong
Published: September 2023

The MOS‐only memristor only uses the transistor's intrinsic capacitance to realize the memristor's memory effect, which is beneficial to increase its operating frequency and reduce its occupied chip area. This paper proposes a GHz‐level MOS‐only memristor emulator (i.e., PGME and NGME). PGME/NGME consists of three/four MOSFETs without any external elements and power supplies. The operating frequency of PGME/NGME is high up to 5 GHz. When the three/four MOSFETs in PGME are pch_hvts of TSMC's 65‐nm process, the occupied chip areas of PGME‐3, PGME‐4A, and PGME‐4B are 3.9 ∗ 2.7 
m2, 4.3 ∗ 3.3 
m2, and 4.3 ∗ 4.4 
m2, respectively. The minimum step time of material implication circuit based on PGME‐3 and NGME‐3 is only 70 ps. Additionally, a chaotic oscillator circuit based on PGME‐4A is presented and verified with discrete p‐channel MOSFETs of CD4007.
Genomic signatures of bottleneck and founder effects in dingoes
Authors: Kumar Manoharan , Conroy Gabriel , Ogbourne Steven , Cairns Kylie , Borburgh Liesbeth , Subramanian Sankar
Published: September 2023

Dingoes arrived in Australia during the mid‐Holocene and are the top‐order terrestrial predator on the continent. Although dingoes subsequently spread across the continent, the initial founding population(s) could have been small. We investigated this hypothesis by sequencing the whole genomes of three dingoes and also obtaining the genome data from nine additional dingoes and 56 canines, including wolves, village dogs and breed dogs, and examined the signatures of bottlenecks and founder effects. We found that the nucleotide diversity of dingoes was low, 36% less than highly inbred breed dogs and 3.3 times lower than wolves. The number of runs of homozygosity (RoH) segments in dingoes was 1.6–4.7 times higher than in other canines. While examining deleterious mutational load, we observed that dingoes carried elevated ratios of nonsynonymous‐to‐synonymous diversities, significantly higher numbers of homozygous deleterious Single Nucleotide Variants (SNVs), and increased numbers of loss of function SNVs, compared to breed dogs, village dogs, and wolves. Our findings can be explained by bottlenecks and founder effects during the establishment of dingoes in mainland Australia. These findings highlight the need for conservation‐based management of dingoes and the need for wildlife managers to be cognisant of these findings when considering the use of lethal control measures across the landscape.
Shading contributes to Sphagnum decline in response to warming
Authors: Norby Richard J. , Baxter Taylor , Živković Tatjana , Weston David J.
Published: September 2023

Experimental warming of an ombrotrophic bog in northern Minnesota has caused a rapid decline in the productivity and areal cover of Sphagnum mosses, affecting whole‐ecosystem carbon balance and biogeochemistry. Direct effects of elevated temperature and the attendant drying are most likely the primary cause of the effects on Sphagnum, but there may also be responses to the increased shading from shrubs, which increased with increasing temperature. To evaluate the independent effects of reduction in light availability and deposition of shrub litter on Sphagnum productivity, small plots with shrubs removed were laid out adjacent to the warming experiment on hummocks and hollows in three blocks and with five levels of shading. Four plots were covered with neutral density shade cloth to simulate shading from shrubs of 30%–90% reduction in light; one plot was left open. Growth of Sphagnum angustifolium/fallax and S. divinum declined linearly with increasing shade in hollows, but there was no response to shade on hummocks, where higher irradiance in the open plots may have been inhibitory. Shading caused etiolation of Sphagnum—they were thin and spindly under the deepest shade. A dense mat of shrub litter, corresponding to the amount of shrub litter produced in response to warming, did not inhibit Sphagnum growth or cause increases in potentially toxic base cations. CO2 exchange and chlorophyll‐a fluorescence of S. angustifolium/fallax from the 30% and 90% shade cloth plots were measured in the laboratory. Light response curves indicate that maximal light saturated photosynthesis was 42% greater for S. angustifolium/fallax grown under 30% shade cloth relative to plants grown under 90% shade cloth. The response of Sphagnum growth in response to increasing shade is consistent with the hypothesis that increased shade resulting from shrub expansion in response to experimental warming contributed to reduced Sphagnum growth.
Big data financial transactions and GDP nowcasting: The case of Turkey
Authors: Barlas Ali B. , Mert Seda Guler , Isa Berk Orkun , Ortiz Alvaro , Rodrigo Tomasa , Soybilgen Baris , Yazgan Ege
Published: September 2023

We use aggregated information from individual‐to‐firm and firm‐to‐firm transactions from the Garanti BBVA Bank to simulate domestic private demand and estimate aggregate consumption and investment for Turkey's quarterly national accounts in real time. We show that these big data variables successfully nowcast official consumption and investment flows. To further validate the usefulness of these indicators, we include both indicators among others which are generally used in gross domestic product (GDP) nowcasting and evaluate their contribution to nowcasting power of Turkish GDP by combining both linear and nonlinear models. The results are successful and confirm the usefulness of consumption and investment banking transactions for nowcasting purposes. These big data are valuable, especially at the beginning of the nowcasting process, when the traditional hard data are scarce. Accordingly, this information is especially relevant for countries with longer statistical release lags, such as emerging markets.
Saponins from Momordica charantia exert hypoglycemic effect in diabetic mice by multiple pathways
Authors: Deng Yuanyuan , Zhang Yan , Liu Guang , Zhou Pengfei , Li Ping , Zhao Zhihao , Zhang Ruifen , Tang Xiaojun , Wang Zhangying , Wei Zhencheng , Zhang Mingwei
Published: September 2023

The antidiabetic activity of saponins extracted from Momordica charantia (MCS) on streptozotocin‐induced diabetic mice was investigated in order to elucidate the mechanism of MCS for exerting hypoglycemic effects. Saponins were first extracted from M. charantia L. and their composition was analyzed. The diabetic Kunming mice were fed low‐dose saponins from M. charantia L. and high‐dose MCS, using normal mice and diabetic mice as controls. Body weight, blood glucose level, oral glucose tolerance, serum C‐peptide level, hepatic antioxidant capacity, hepatic glycogen and hexokinase in liver tissues, serum blood lipid level, and alpha‐glucosidase activity in small intestines were measured, and microstructure of pancreatic islet was analyzed. The results showed that the total content of seven triterpenoid compounds in MCS was 18.24 μg/mg, with Momordicoside K having the highest content at 11.66 μg/mg. Diabetic mice treated with MCS at 100 and 200 mg/kg body weight daily for 30 days showed a maximum glucose reduction (p < .05) of 12.63% and 26.47%, respectively. MCS significantly decreased levels of postprandial hyperglycemia, serum lipid, α‐glucosidase activity, and liver malondialdehyde. Additionally, levels of serum C‐peptide and liver glycogen, as well as hexokinase and antioxidant enzyme activity, were significantly increased compared to the diabetic control groups. Histopathological results showed that MCS markedly reduced degenerative changes in islet β‐cells. It is concluded that MCS exerts antidiabetic effects by improved hypoglycemic, hypolipidemic, and antioxidant effects, increased hexokinase activity and glycogen synthesis, and enhanced reparative effects on the histological architecture and insulin secretion function of the pancreas.
Nonclinical safety assessment of an mRNA Covid‐19 vaccine candidate following repeated administrations and biodistribution
Authors: Broudic Karine , Laurent Sébastien , Perkov Vladimir , Simon Charlene , Garinot Marie , Truchot Nathalie , Latour Julie , Désert Paul
Published: September 2023

Messenger RNA (mRNA) vaccines have demonstrated efficacy against Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) in humans. mRNA technology holds tremendous potential for rapid control and prevention of emergencies due to its flexibility with respect to production, application, and design for an efficacious and safe use in humans. We assessed the toxicity and biodistribution of MRT5500, an mRNA vaccine encoding for the full‐length of the SARS‐CoV‐2 spike protein and delivered by lipid nanoparticles (LNPs) containing a novel ionizable lipid, Lipid‐1 in preclinical animal models. In the repeated dose toxicity study, rabbits received three intramuscular (IM) injections of MRT5500 at 3‐week interval followed by a 4‐week observation period. In an exploratory biodistribution study in mice receiving a single IM injection of an mRNA encoding luciferase encapsulated in an LNP containing Lipid‐1, the expression of the luciferase protein was monitored in vivo and ex vivo at several time points. In the regulatory biodistribution study in rabbits receiving a single IM injection of MRT5500, the quantification of the mRNA and the ionizable Lipid‐1 were monitored in the same organs and time points as in the exploratory biodistribution study. MRT5500 was safe and well‐tolerated with a transient acute phase response/inflammation and an expected vaccine‐related immunological response, typical of those observed following a vaccine administration. The biodistribution data demonstrated that the mRNA and Lipid‐1 components of the vaccine formulations were mainly detected at the injection site and in the draining lymph nodes. These results support the use of MRT5500 and its deployment into clinical trials.
Adaptive, behavioral, and cognitive outcomes in individuals with fragile X syndrome with varying autism severity
Authors: Aishworiya Ramkumar , Tak Ye Eun , Ponzini Matthew Dominic , Biag Hazel Maridith Barlahan , Salcedo‐Arellano Maria Jimena , Kim Kyoungmi , Tassone Flora , Schneider Andrea , Thurman Angela John , Abbeduto Leonard , Hessl David , Randol Jamie Leah , Bolduc Francois V. , Lippe Sarah , Hagerman Paul , Hagerman Randi
Published: September 2023

This study aimed to determine the association between severity of autism spectrum disorder (ASD) and cognitive, behavioral, and molecular measures in individuals with fragile X syndrome (FXS). Study inclusion criteria included individuals with FXS and (1) age 6–40 years, (2) full‐scale IQ < 84, and (3) language ≥3‐word phrases. ASD symptom severity was determined by Autism Diagnostic Observation Schedule‐2 (ADOS‐2). Other measures identified non‐verbal IQ, adaptive skills, and aberrant behaviors. Molecular measures included blood FMR1 and CYFIP1 mRNA levels, FMRP and MMP9 levels. Analysis of variance (ANOVA) and Spearman's correlations were used to compare ASD severity groups. Data from 54 individuals was included with no/mild (N = 7), moderate (N = 18), and severe (N = 29) ASD. Individuals with high ASD severity had lower adaptive behavior scores (47.48 ± 17.49) than the no/mild group (69.00 ± 20.45, p = 0.0366); they also had more challenging behaviors, lethargy, and stereotypic behaviors. CYFIP1 mRNA expression levels positively correlated with the ADOS‐2 comparison score(r2 = 0.33, p = 0.0349), with no significant correlations with other molecular markers. In conclusion, autism symptom severity is associated with more adverse cognitive and adaptive skills and specific behaviors in FXS, whereas CYFIP1 mRNA expression levels may be a potential biomarker for severity of ASD in FXS.
Unique architecture of microbial snottites from a methane driven biofilm revealed by confocal microscopy
Authors: Neu Thomas R. , Kuhlicke Ute , Karwautz Clemens , Lüders Tillmann
Published: September 2023

Microbial biofilms occur in many shapes and different dimensions. In natural and semi‐artificial caves they are forming pendulous structures of 10 cm and more. In this study a methane driven microbial community of a former medicinal spring was investigated. The habitat was completely covered by massive biofilms and snottites with a wobbly, gelatinous appearance. By using fluorescence techniques in combination with confocal laser scanning microscopy the architecture of these so far unknown snottites was examined. The imaging approaches applied comprised reflection of geogenic and cellular origin, possible autofluorescence, nucleic acid staining for bacterial cells, protein staining for bacteria and extracellular fine structures, calcofluor white for β 1 → 3, β 1 → 4 polysaccharide staining for possible fungi as well as lectin staining for the extracellular biofilm matrix glycoconjugates. The results showed a highly complex, intricate structure with voluminous, globular, and tube‐like glycoconjugates of different dimensions and densities. In addition, filamentous bacteria seem to provide additional strength to the snottites. After screening with all commercially available lectins, by means of fluorescence lectin barcoding and subsequent fluorescence lectin binding analysis, the AAL, PNA, LEA, and Ban lectins identified α‐Fuc, β‐Gal, β‐GlcNAc, and α‐Man with α‐Fuc as a major component. Examination of the outer boundary with fluorescent beads revealed a potential outer layer which could not be stained by any of the fluorescent probes applied. Finally, suggestions are made to further elucidate the characteristics of these unusual microbial biofilms in form of snottites.

Research Highlights

The gelatinous snottites revealed at the microscale a highly complex structure not seen before.

The extracellular matrix of the snottite biofilm was identified as clusters of different shape and density.

The matrix of snottites was examined by taking advantage of 78 fluorescently‐labeled lectins.

The extracellular matrix glycoconjugates of snottites identified comprised: α‐Fuc, β‐Gal, β‐GlcNAc, and α‐Man.

Probing the snottite outer surface indicated an additional unknown stratum.
Hepatic abscess induced by gastric cancer mimicking differentiated hepatocellular carcinoma
Authors: Kishimoto Takuya , Morita Toshihiro , Yazumi Shujiro
Published: September 2023

A 58‐year‐old man was referred to our hospital with right abdominal pain. Contrast‐enhanced computed tomography (CECT) showed a rim‐enhanced lesion with a fluid collection in the right hepatic lobe. Upper gastrointestinal endoscopy revealed a Borrmann type 1 tumor on the middle gastric body, identified as an adenocarcinoma on pathology. The patient underwent percutaneous transhepatic abscess drainage and was treated with antibiotics. Two weeks after drainage, CECT revealed shrinkage of the abscess; however, the wall showed contrast enhancement. Needle biopsy was performed for the liver tumor, and it suggested the possibility of highly differentiated hepatocellular carcinoma. The patient first underwent gastrectomy, and the liver tumor was followed with CECT. Two months after surgery, CECT revealed that the liver tumor had vanished. Liver abscesses and infectious tumors can be difficult to differentiate between; therefore, careful scrutiny is essential before treatment.
Survey of maternal anxiety and perceptions towards foetal MRI and pre‐scan education
Authors: Plunkett Stephanie , Dobeli Karen , Prior Marita , Tusek Xanthe
Published: September 2023

Introduction

Foetal MRI scans can induce feelings of fear, concern and anxiety in pregnant patients. The aim of this research was to determine if providing patients with an information leaflet reduced maternal anxiety regarding foetal MRI.

Methods

A prospective, three‐arm comparative pilot study was performed in the MRI department of a quaternary public hospital in Brisbane, Australia. Three groups of 30 participants (total 90 participants) received differing levels of information about foetal MRI: Group A – no foetal‐MRI specific information (current practice at the site); Group B – a basic information leaflet; Group C – a comprehensive information leaflet. All participants completed a survey that explored their pre‐scan anxiety immediately after their MRI scan.

Results

Over 50% of participants in each group felt anxious before the MRI. Participants expressed anxiety towards the general process of the MRI, the outcome or results of the scan, and the safety of the modality. The basic and comprehensive leaflets were both efficacious in reducing anxiety for the majority of participants.

Conclusions

Whilst not all patients express anxiety regarding MRI scans, emotional distress surrounding the entire process is prevalent. Providing patients with comprehensive information about what the MRI scan entails (including the scan environment and duration, positioning, breath‐holding requirements, and foetal safety) reduces anxiety for most patients. These findings can be used to determine ways in which reduction of anxiety improves the patient experience.
Infection with COVID‐19 is no longer a public emergency: But what about degenerative dementia?
Authors: Yulug Burak , Ayyıldız Behçet , Ayyıldız Sevilay , Sayman Dila , Salar Ali Behram , Cankaya Seyda , Ozdemir Oktem Ece , Ozsimsek Ahmet , Kurt Cagla Ceren , Lakadamyalı Hatice , Akturk Aynur , Altay Özlem , Hanoglu Lutfu , Velioglu Halil Aziz , Mardinoglu Adil
Published: September 2023

Although no longer considered a public health threat, post‐COVID cognitive syndrome continues to impact on a considerable proportion of individuals who were infected with COVID‐19. Recent studies have also suggested that COVID may be represent a critical risk factor for the development of Alzheimer's disease (AD). We compared 17 COVID patients with 20 controls and evaluated the effects of COVID‐19 on general cognitive performance, hippocampal volume, and connections using structural and seed‐based connectivity analysis. We showed that COVID patients exhibited considerably worse cognitive functioning and increased hippocampal connectivity supported by the strong correlation between hippocampal connectivity and cognitive scores. Our findings of higher hippocampal connectivity with no observable hippocampal morphological changes even in mild COVID cases may be represent evidence of a prestructural compensatory mechanism for stimulating additional neuronal resources to combat cognitive dysfunction as recently shown for the prodromal stages of degenerative cognitive disorders. Our findings may be also important in light of recent data showing that other viral infections as well as COVID may constitute a critical risk factor for the development of AD. To our knowledge, this is the first study that investigated network differences in COVID patients, with a particular focus on compensatory hippocampal connectivity.
FOXD2 regulations IQGAP3 mediated Ca2+ signaling pathway to facilitate gastric adenocarcinoma cell promotion
Authors: Fei Ting , Zhou En‐Cheng , Wang Xiao‐Jun
Published: September 2023

As a transcriptional factor, the Forkhead box (FOX) gene family is closely connected with apoptosis, proliferation, and other cellular processes. FOXD2, as one descendant of the FOX gene family, has been mentioned in many articles to show a high expression in several cancers. However, whether FOXD2 has a connection with gastric adenocarcinoma remains an unanswered question. Expression of FOXD2 and IQGAP3 in gastric adenocarcinoma was evaluated by bioinformatics analysis, which was further detected by real‐time quantitative PCR (qRT‐PCR) and western blot. The downstream target genes of FOXD2 were also mined by bioinformatics analysis. Pathway enrichment analysis was then performed on the target genes. Chromatin immunoprecipitation assay (ChIP) and dual‐luciferase reporter assay were conducted to validate the regulatory relationship between FOXD2 and its downstream target gene IQGAP3. Methyl thiazolyl tetrazolium assay (MTT), combined with cell colony formation assay, was employed to assess the effect of FOXD2 and IQGAP3 on the proliferation of gastric adenocarcinoma cells. Intracytoplasmic Ca2+ concentration was measured by Fluo‐3 fluorescence staining. FOXD2 showed a high expression in gastric adenocarcinoma tissues and cells, and FOXD2 silencing considerably attenuated gastric adenocarcinoma cell proliferation. IQGAP3, a downstream target gene of FOXD2, had a positive connection with the expression of FOXD2. The binding relationship between FOXD2 and the promoter region of IQGAP3 was further verified by ChIP and dual‐luciferase reporter assays. The results of cell function experiments indicated that FOXD2 could promote gastric adenocarcinoma cell proliferation by transcriptionally activating IQGAP3 to induce an increase in intracellular Ca2+ level. This study confirmed that FOXD2 increased intracellular Ca2+ level through transcriptional activation of IQGAP3, which in turn propelled the proliferation of gastric adenocarcinoma cells, revealing the considerable significance of FOXD2 in the development of gastric adenocarcinoma.