bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly sensitive MoS2 photodetector on polarized thin-film lithium niobate with extremely low dark current
Authors: Liu Yifan , Chen Haiwei , Zhang Yuwei , Zhou Tao , Zhou Jun , Zhao Bei , Wang Wenhui , Lu Junpeng , Ni Zhenhua , Wan Dongyang
Published: July 2024

To obtain high performance optoelectronic devices, ferroelectric materials have received a lot of attention due to the various emerging effects on channel materials induced by the ferroelectric polarization. In this work, a special photodetector with the channel material of a triple-layer MoS2 on a polarized LiNbO3 substrate was fabricated. The device has a high responsivity of 113.1[Formula: see text]A/W and a high specific detectivity of up to [Formula: see text] Jones under red illumination, while maintaining the rise and fall time of 32 and 22[Formula: see text]ms, respectively. Meanwhile, the dark current of this device can be as low as [Formula: see text][Formula: see text]A with a bias of 5.0[Formula: see text]V because the channel material MoS2 is almost depleted under the internal electrical field induced by the polarized LiNbO3. This work promises a feasible way for the future development of integrated high-sensitivity photodetectors.
ANALYZING THE OCCURRENCE OF BIFURCATION AND CHAOTIC BEHAVIORS IN MULTI-FRACTIONAL-ORDER STOCHASTIC GINZBURG–LANDAU EQUATIONS
Authors: SUN YIQUN , QI JIANMING , CUI QINGHUA
Published: July 2024

The main novelty of this paper lies in five aspects. (1) Our study on the fractional-order derivative stochastic Ginzburg–Landau equation (FODSGLE) has resulted in numerous exact solutions using Jacobian elliptic functions (JEFs). These solutions offer valuable insights into complex physical phenomena and have practical implications across various fields. (2) By examining the effect of noise on FODSGLE solutions, we found consistent behavior regardless of the form of fractional derivatives. As noise intensity increases, the solutions deteriorate and tend toward zero. This study contributes to the existing literature by providing new insights and surpassing previous efforts in understanding the dynamics of FODSGLE. (3) Our research investigates how fractional order affects noise in solutions of the FODSGLE. Surprisingly, we found that changes in the fractional order ([Formula: see text]) have minimal influence on the system when the noise intensity ([Formula: see text]) is fixed. This indicates an aspect that has not been addressed extensively in existing literatures. (4) We compare different types of fractional derivatives within the context of the FODSGLE, presenting a novel contribution, while keeping the noise intensity or fractional order fixed. Our results demonstrate that the CFOD closely aligns with the MFOD, while displaying more differences with the solutions obtained using the BFOD. This comparison sheds light on an aspect that has not been thoroughly investigated in previous literatures. (5) This paper delves into the phase portraits of the FODSGLE and investigates the associated sensitivity and chaotic behaviors. Notably, previous studies on the stochastic Ginzburg–Landau equation (SGLE) have not extensively examined this aspect. By analyzing the phase portraits, we gain valuable insights into the dynamics and stability of FODSGLE solutions, uncovering intricate behaviors within the system. Our exploration of sensitivity and chaotic behaviors adds another dimension to understanding the (FODSGLE), laying a foundation for further research in this domain.
NEUTRON POINT KINETICS MODEL WITH A DISTRIBUTED-ORDER FRACTIONAL DERIVATIVE
Authors: GODÍNEZ F. A. , FERNÁNDEZ-ANAYA G. , QUEZADA-GARCÍA S. , QUEZADA-TÉLLEZ L. A. , POLO-LABARRIOS M. A.
Published: July 2024

In this paper, the solutions of an extended form of the Fractional-order Neutron Point Kinetics (FNPK) equation in terms of Caputo-time derivatives of the same order are investigated. Instead of using a Caputo derivative, a distributed-order fractional derivative in the Caputo sense was employed in the term of the FNPK equation which is multiplied by the reactivity. This term plays an important role in the description of neutron kinetics during the start-up, shutdown, and steady-state processes in nuclear reactors. The extended (DFNPK) model was solved using the beta, normal, bimodal and Dirac delta distributions to investigate their effect on the transient state solutions of the neutron density. Regardless of the distribution used, the most significant finding is that a destabilizing effect on the neutron density is induced when the mode (or the instant of application of the Dirac delta) of the distribution tends to one while maintaining the orders of the Caputo-time derivatives constant. What defines the destabilizing effect are large magnitude oscillations, a rapid decay, and an oscillation-free steady state with a monotonic increase that is parallel to but somewhat above the trend determined by the FNPK equation. The extended model is anticipated to be effective for modeling neutron density dispersion in a highly heterogeneous medium that may be described using distributed derivatives.
Partial order on involutive permutations and double Schubert cells
Authors: Smirnov Evgeny
Published: July 2024

As shown by Melnikov, the orbits of a Borel subgroup acting by conjugation on upper-triangular matrices with square zero are indexed by involutions in the symmetric group. The inclusion relation among the orbit closures defines a partial order on involutions. We observe that the same order on involutive permutations also arises while describing the inclusion order on [Formula: see text]-orbit closures in the direct product of two Grassmannians. We establish a geometric relation between these two settings.
Jan Mayen Microcontinent Composite Tectono-Sedimentary Element and Jan Mayen Prograded Margin Tectono-Sedimentary Element, Greenland Sea
Authors: Brekke Harald
Published: July 2024

The Jan Mayen Micro-Continent (JMMC) is the result of two Cainozoic phases of continental breakup, and subsequent seafloor spreading. The first established a spreading ridge system consisting of the Reykjanes, Ægir, and Mohn spreading ridges between Norway and Greenland in early Eocene. The second phase established the Kolbeinsey Ridge in Oligocene/Miocene separating the JMMC form Greenland. Two major stratigraphic elements are established accordingly, the Jan Mayen Micro-Continent Composite Tectono-Sedimentary Element (JMMC CTSE) for the Middle Devonian to Miocene succession, and the Jan Mayen Prograded Margin Tectono-Sedimentary Element (JMPM TSE) for the Miocene to Holocene succession. OBS refraction data show that the JMMC is underlain by a generally thickened crust. Plate reconstructions show that this crust most likely is a remnant of continental crust rifted off East Greenland, and thereby, consist of rocks that correlates with the Late Palaeozoic and Mesozoic strata stratigraphy of the conjugate margins of East Greenland and Norway known to be hydrocarbon. The arrival of the Iceland hot spot and the breakup magmatism greatly influenced the historic and current heat flow. Published maturation models and play analysis, show that there is a potential for oil and gas in the Jan Mayen Ridge within the JMMC.
Biofabrication of Living Actuators
Authors: Raman Ritu
Published: July 2024

The impact of tissue engineering has extended beyond a traditional focus in medicine to the rapidly growing realm of biohybrid robotics. Leveraging living actuators as functional components in machines has been a central focus of this field, generating a range of compelling demonstrations of robots capable of muscle-powered swimming, walking, pumping, gripping, and even computation. In this review, we highlight key advances in fabricating tissue-scale cardiac and skeletal muscle actuators for a range of functional applications. We discuss areas for future growth including scalable manufacturing, integrated feedback control, and predictive modeling and also propose methods for ensuring inclusive and bioethics-focused pedagogy in this emerging discipline. We hope this review motivates the next generation of biomedical engineers to advance rational design and practical use of living machines for applications ranging from telesurgery to manufacturing to on- and off-world exploration.
Next-Generation Vaccine Development with Nanomaterials: Recent Advances, Possibilities, and Challenges
Authors: Shetty Shamitha , Alvarado Pablo Cordero , Pettie Deleah , Collier Joel H.
Published: July 2024

Nanomaterials are becoming important tools for vaccine development owing to their tunable and adaptable nature. Unique properties of nanomaterials afford opportunities to modulate trafficking through various tissues, complement or augment adjuvant activities, and specify antigen valency and display. This versatility has enabled recent work designing nanomaterial vaccines for a broad range of diseases, including cancer, inflammatory diseases, and various infectious diseases. Recent successes of nanoparticle vaccines during the coronavirus disease 2019 (COVID-19) pandemic have fueled enthusiasm further. In this review, the most recent developments in nanovaccines for infectious disease, cancer, inflammatory diseases, allergic diseases, and nanoadjuvants are summarized. Additionally, challenges and opportunities for clinical translation of this unique class of materials are discussed.
It’s all in the timing: delayed feedback in autism may weaken predictive mechanisms during contour integration
Authors: Knight Emily J. , Altschuler Ted S. , Molholm Sophie , Murphy Jeremy W. , Freedman Edward G. , Foxe John J.
Published: July 2024

Children with autism often present with an atypical visual perceptual style that emphasizes parts or details over the whole. Using electroencephalography (EEG), this study identifies delays in the visual feedback from higher-order sensory brain areas to primary sensory regions. Because this type of visual feedback is thought to carry information about prior sensory experiences, individuals with autism may have difficulty efficiently using prior experience or putting together parts into a whole to help make sense of incoming new visual information. This provides empirical neural evidence to support theories of disrupted sensory perception mechanisms in autism.
Radiological Evaluation of the Accuracy of Demirjian, Nolla, and Willems Methods for Dental Age Estimation in 3–17‐Year‐Old Iranian Children
Authors: Pliska Benjamin , Nahvi Azam , Pakdaman Nikta , Dadgar Sepideh , Aryana Mehdi , Sobouti Farhad
Published: July 2024

Background: The stage of tooth formation is one of the most reliable indicators for predicting a patient’s developmental age by radiographs. This study compared the accuracy of three distinct dental age estimation methods (Demirjian, Nolla, and Willems) in children aged 3–17 in the northern Iranian population.

Methods: This cross‐sectional study examined panoramic radiographs of 434 children aged 3–17 from Mazandaran Province, Iran, who had teeth 31–37 present on the left mandible. This study employed the Demirjian, Nolla, and Willems methods to estimate the dental age of the sample and compare it with the chronological age. The data were analyzed using SPSS v16. A paired t‐test was used to compare chronological and dental ages. The Pearson correlation was used to correlate the chronological and dental ages. The errors of different methods were compared using the Wilcoxon test. P values < 0.05 were considered significant for all tests except Wilcoxon. For Wilcoxon, a P value < 0.017 was considered significant.

Results: The three methods presented differing mean estimated ages. The Demirjian method delivered the highest mean, and all three methods differed significantly when compared in pairs. The results showed that the Demirjian method overestimated chronological age by 0.25 years (P < 0.001) in girls and 0.09 years (P = 0.28) in boys. The Willems method underestimated chronological age by 0.05 years (P = 0.47) in girls and 0.12 years (P = 0.13) in boys. The Nolla method underestimated chronological age by 0.41 years (P < 0.001) in girls and 0.40 years (P < 0.001) in boys. The accuracy of each method varied with the patient’s age.

Conclusion: According to the findings, the Willems method outperformed the Demirjian method, and the Demirjian method exceeded the Nolla method for estimating dental age in Iranian children aged 3–17. Overall, the Demirjian method overestimated the age of the study population, whereas the other two underestimated it.
Integrative Multiomics Analyses Identify Molecular Subtypes of Head and Neck Squamous Cell Carcinoma with Distinct Therapeutic Vulnerabilities
Authors: Diao Pengfei , Dai Yibin , Wang An , Bu Xiaoxuan , Wang Ziyu , Li Jin , Wu Yaping , Jiang Hongbing , Wang Yanling , Cheng Jie
Published: July 2024

Substantial heterogeneity in molecular features, patient prognoses, and therapeutic responses in head and neck squamous cell carcinomas (HNSCC) highlights the urgent need to develop molecular classifications that reliably and accurately reflect tumor behavior and inform personalized therapy. Here, we leveraged the similarity network fusion bioinformatics approach to jointly analyze multiomics datasets spanning copy number variations, somatic mutations, DNA methylation, and transcriptomic profiling and derived a prognostic classification system for HNSCC. The integrative model consistently identified three subgroups (IMC1-3) with specific genomic features, biological characteristics, and clinical outcomes across multiple independent cohorts. The IMC1 subgroup included proliferative, immune-activated tumors and exhibited a more favorable prognosis. The IMC2 subtype harbored activated EGFR signaling and an inflamed tumor microenvironment with cancer-associated fibroblast/vascular infiltrations. Alternatively, the IMC3 group featured highly aberrant metabolic activities and impaired immune infiltration and recruiting. Pharmacogenomics analyses from in silico predictions and from patient-derived xenograft model data unveiled subtype-specific therapeutic vulnerabilities including sensitivity to cisplatin and immunotherapy in IMC1 and EGFR inhibitors (EGFRi) in IMC2, which was experimentally validated in patient-derived organoid models. Two signatures for prognosis and EGFRi sensitivity were developed via machine learning. Together, this integrative multiomics clustering for HNSCC improves current understanding of tumor heterogeneity and facilitates patient stratification and therapeutic development tailored to molecular vulnerabilities.

Significance: Head and neck squamous cell carcinoma classification using integrative multiomics analyses reveals subtypes with distinct genetics, biological features, clinicopathological traits, and therapeutic vulnerabilities, providing insights into tumor heterogeneity and personalized treatment strategies.
Augmenting CAR T-cell Functions with LIGHT
Authors: Cai Winson , Tanaka Kento , Mi Xiaoli , Rajasekhar Vinagolu K. , Khan Jonathan F. , Yoo Sarah , de Stanchina Elisa , Rahman Jahan , Mathew Serena , Abrahimi Parwiz , Souness Sydney , Purdon Terence J. , McDowell James R. , Meyerberg Jeremy , Fujino Takeshi , Healey John H. , Abdel-Wahab Omar , Scheinberg David A. , Brentjens Renier J. , Daniyan Anthony F.
Published: July 2024

Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both lymphotoxin-β receptor on cancer cells and herpes virus entry mediator on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with lymphotoxin-β receptor on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells’ proliferation and cytolytic profile. These data indicate that LIGHT-expressing CAR T cells may provide a way to eliminate antigen-negative tumor cells to prevent antigen-negative disease relapse.
Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals
Authors: Chen Ming Hui , Deng Ellen S. , Yamada Jessica M. , Choudhury Sangita , Scotellaro Julia , Kelley Lily , Isselbacher Eric , Lindsay Mark E. , Walsh Christopher A. , Doan Ryan N.
Published: July 2024

Background

Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center.

Methods and Results

One hundred eighty‐one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age‐ and sex‐matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44,
P
=4.6×10
−6
[95% CI, 1.67–3.58]) and also somatic mosaic variants (OR, 4.71,
P
=0.026 [95% CI, 1.20–18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were
FLNA
(encoding Filamin A),
NOTCH3
(encoding Notch receptor 3), and
FBN1
(encoding Fibrillin‐1). There was increased frequency of both missense and loss of function variants in TAA individuals.

Conclusions

Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.
Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real‐World Data
Authors: Müller Maximilian Leo , Latinova Ekaterina , Brand Anna , Mattig Isabel , Spethmann Sebastian , Messroghli Daniel , Hahn Katrin , Landmesser Ulf , Heidecker Bettina
Published: July 2024

Background

Results from ATTR‐ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy) indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR‐CA). However, real‐world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR‐CA treated with tafamidis in a real‐world setting and assess the prognostic role of the New York Heart Association (NYHA) classification.

Methods and Results

We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR‐CA (wild‐type or variant) treated with tafamidis. Clinical outcome was tracked through follow‐up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan‐Meier analysis estimated overall and MACE‐free survival including NYHA subgroups (NYHA I/II versus NYHA III).

One hundred sixty‐seven patients with ATTR‐CA (94.6% wild‐type) were enrolled and followed for a median of 539 [323–869] days. Median overall survival was not reached. Estimated 1‐year, 2‐year, and 5‐year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (
P
=0.002). Median MACE‐free survival time was 1082 (95% CI, 962–1202) days. MACE‐free survival was higher in the NYHA I/II subgroup (
P
<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48–23.18;
P
=0.012) and 3.95 (95% CI, 1.99–7.84;
P
<0.001), NYHA III was an independent predictor of death and MACE.

Conclusions

Treatment of ATTR‐CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.
Macrobrachium ngankeeae, a new species of freshwater shrimp (Crustacea: Decapoda: Palaemonidae) from Papua Barat Province, Indonesia
Authors: MAZANCOURT VALENTIN DE , MARQUET GERARD , WOWOR DAISY , KEITH PHILIPPE
Published: July 2024

A new freshwater prawn, Macrobrachium ngankeeae n. sp., is described from two rivers in the Kaimana Regency on the southern coast of Papua Barat Province, Indonesia. The new species belongs to the Macrobrachium placidulum species-group, but it can be easily distinguished from the other members of this group by having fewer postorbital teeth and the epigastric tooth placed more anteriorly with a relatively shorter epigastric length, i.e. 0.23–0.27 of carapace length (vs 0.24–0.55 in the other species members). Other distinguishing morphological characters and a molecular analysis of this new species are discussed. A key to the species of the M. placidulum species-group is also provided.
Taxonomic notes on three species of Tiwaripotamon Bott, 1970 (Crustacea: Brachyura: Potamidae) from Vietnam and China, one of which is new to science
Authors: NG PETER K. L.
Published: July 2024

A new species of semiterrestrial freshwater crab, Tiwaripotamon nganima n. sp. is described from northern Vietnam. The gonopods of the new species most closely resemble T. annamense (Balss, 1914) originally collected from Phuc-Son in Annam, central Vietnam, but can easily be distinguished as it has the median lobe on the posterior margin of the epistome being more projecting, the male pleon is proportionately more quadrate and less wide, the basal part of the male first gonopod has the median part of the subterminal segment more strongly curved, and the outer surface of the basal part of the terminal segment of the male first gonopod is prominently swollen. The taxonomy of two species described from southern China, T. pingguoense Dai & Naiyanetr, 1994, and T. xiurenense Dai & Naiyanetr, 1994, is also clarified after re-examination of type specimens and photographs of the original material; both species are redescribed and refigured.
On the genus Lyphira Galil, 2009 (Crustacea: Brachyura: Leucosiidae), with descriptions of four new species from the West Pacific
Authors: RAHAYU DWI LISTYO , NG PETER K. L.
Published: July 2024

The taxonomy of the shallow water leucosiid crab, Lyphira heterograna (Ortmann, 1892), is revised on the basis of the lectotype and material from Japan, southern China, Hong Kong and Southeast Asia previously identified with this species. Six species are now recognised in the Lyphira heterograna species-group, of which four are new species: L. chomel n. sp., L. ngankee n. sp., L. linda n. sp., and L. bellagrana n. sp. Philyra acutidens Chen, 1987, described from the Yellow Sea and previously synonymized with L. heterograna, is recognised as a valid species. These species are redescribed, figured and compared with congeners.
Description of a new genus and new species of freshwater crab (Crustacea, Decapoda, Potamidae) from Yunnan, China
Authors: YEO DARREN C. J. , ZHOU XIANMIN , NG PETER K. L.
Published: July 2024

A new genus and new species of freshwater crab is described from Yunnan Province, China. Proboscimon keeae gen. n., sp. n. belongs to a group of Chinese genera that lack a flagellum on the exopod of the third maxilliped. Of these, it is superficially most similar to Arquatopotamon Chu, Zhou & Sun, 2017 from Yunnan, but is distinguished from it and other genera mainly by the form of its male first pleopod as well as characters of the carapace, thoracic sternum, and male sternopleonal cavity.
A new intertidal barnacle, Chthamalus ngankeeae sp. nov. (Balanomorpha: Chthamalidae) from the Malaysian Peninsula and western Borneo waters
Authors: CHAN BENNY K. K. , TSAI PEI-CHEN , TSAO YAO-FENG
Published: July 2024

The present study identified a new barnacle species from Malaysian waters, Chthamalus ngankeeae sp. nov., on morphological and molecular grounds. Chthamalus ngankeeae sp. nov. is an intertidal species that is abundant on high shores, above the oyster zone. Chthamalus ngankeeae sp. nov. has two morphotypes, based on shell colour. Brown morphs have brown shells with pale brown ridges and look similar to Microeuraphia withersi (Pilsbry, 1916). Chthamalus ngankeeae sp. nov. has four teeth on the mandible, while M. withersi has but three. White morphs of C. ngankeeae sp. nov. possess white shells with gray ridges. The white morph of C. ngankeeae sp. nov. is similar to C. moro Pilsbry, 1916, but a major morphological difference includes a more prominent articular ridge on the scutum of C. ngankeeae sp. nov. compared to C. moro. Molecular analyses of sequence divergence in the COI and NaK genes of C. ngankeeae sp. nov. with other chthamalids showed that it forms an individual monophyletic group and does not belong to any of the cryptic lineages of C. moro, supporting its designation as a new species.
Subpolar North Atlantic Mean State Affects the Response of the Atlantic Meridional Overturning Circulation to the North Atlantic Oscillation in CMIP6 Models
Authors: Reintges Annika , Robson Jon I. , Sutton Rowan , Yeager Stephen G.
Published: July 2024

The Atlantic meridional overturning circulation (AMOC) plays an important role in climate, transporting heat and salt to the subpolar North Atlantic. The AMOC’s variability is sensitive to atmospheric forcing, especially the North Atlantic Oscillation (NAO). Because AMOC observations are short, climate models are a valuable tool to study the AMOC’s variability. Yet, there are known issues with climate models, like uncertainties and systematic biases. To investigate this, preindustrial control experiments from models participating in the phase 6 of Coupled Model Intercomparison Project (CMIP6) are evaluated. There is a large, but correlated, spread in the models’ subpolar gyre mean surface temperature and salinity. By splitting models into groups of either a warm–salty or cold–fresh subpolar gyre, it is shown that warm–salty models have a lower sea ice cover in the Labrador Sea and, hence, enable a larger heat loss during a positive NAO. Stratification in the Labrador Sea is also weaker in warm–salty models, such that the larger NAO-related heat loss can also affect greater depths. As a result, subsurface density anomalies are much stronger in the warm–salty models than in those that tend to be cold and fresh. As these anomalies propagate southward along the western boundary, they establish a zonal density gradient anomaly that promotes a stronger delayed AMOC response to the NAO in the warm–salty models. These findings demonstrate how model mean state errors are linked across variables and affect variability, emphasizing the need for improvement of the subpolar North Atlantic mean states in models.
Momelotinib for the treatment of myelofibrosis
Authors: Bose Prithviraj
Published: July 2024

In September 2023, the US Food and Drug Administration approved momelotinib for the treatment of myelofibrosis (MF) with anemia, marking the fourth US regulatory approval of a Janus kinase inhibitor for MF. A positive opinion from the European Medicines Agency followed in November 2023. Momelotinib’s ability to address splenomegaly, symptoms, and anemia, including in patients with thrombocytopenia (with platelet counts of ≥25 × 109/L), the ease of switching from ruxolitinib, and good tolerability uniquely position it to substantially impact the MF treatment landscape.
Growing from common ground: nontuberculous mycobacteria and bronchiectasis
Authors: Van Braeckel Eva , Bosteels Cédric
Published: July 2024

Bronchiectasis and nontuberculous mycobacteria (NTM) are intricately intertwined, with NTM capable of being both a cause and consequence of bronchiectatic disease. This narrative review focuses on the common ground of bronchiectasis and NTM pulmonary disease (NTM-PD) in terms of diagnostic approach, underlying risk factors and treatment strategies. NTM-PD diagnosis relies on a combination of clinical, radiological and microbiological criteria. Although their epidemiology is complicated by detection and reporting biases, the prevalence and pathogenicity of NTM species vary geographically, withMycobacterium aviumcomplex andMycobacterium abscessussubspecies most frequently isolated in bronchiectasis-associated NTM-PD. Diagnosis of nodular bronchiectatic NTM-PD should prompt investigation of host factors, including disorders of mucociliary clearance, connective tissue diseases and immunodeficiencies, either genetic or acquired. Treatment of NTM-PD in bronchiectasis involves a multidisciplinary approach and considers the (sub)species involved, disease severity and comorbidities. Current guideline-based antimicrobial treatment of NTM-PD is considered long, cumbersome and unsatisfying in terms of outcomes. Novel treatment regimens and strategies are being explored, including rifampicin-free regimens and inclusion of clofazimine and inhaled antibiotics. Host-directed therapies, such as immunomodulators and cytokine-based therapies, might enhance antimycobacterial immune responses. Optimising supportive care, as well as pathogen- and host-directed strategies, is crucial, highlighting the need for personalised approaches tailored to individual patient needs. Further research is warranted to elucidate the complex interplay between host and mycobacterial factors, informing more effective management strategies.
WTAP/IGF2BP3-mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c-Myc
Authors: Jin Weiwei , Yao Yanru , Fu Yuhan , Lei Xiangxiang , Fu Wen , Lu Qiliang , Tong Xiangmin , Xu Qiuran , Su Wei , Hu Xiaoge
Published: July 2024

Background

Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated.

Methods

The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC.

Results

GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition.

Conclusions

Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC.
Violence in the emergency department: a quantitative survey study of healthcare providers in India
Authors: Ahluwalia Tania , Singh Sukhpreet , Gandhi Navvin , Toy Serkan , Douglass Katherine , Blanchard Janice , Davey Kevin
Published: July 2024

Background

Workplace violence (WPV) in Emergency Departments (EDs) is an increasingly recognized challenge healthcare providers face in low-resource settings. While studies have highlighted the increased prevalence of WPV in healthcare, most of the existing research has been conducted in developed countries with established laws and repercussions for violence against healthcare providers. More data on WPV against ED providers practicing in low-resource settings is necessary to understand these providers’ unique challenges.

Objective

This study aims to gain insight into the incidence and characteristics of WPV among ED healthcare providers in India.

Methods

This study was conducted at two EDs in geographically distinct regions of India. A survey was designed to assess violence in EDs among healthcare providers. Surveys were distributed to ED workplace providers, completed by hand, and returned anonymously. Data was entered and stored in the RedCAP database to facilitate analysis.

Results

Two hundred surveys were completed by physicians, nurses, and paramedics in Indian EDs. Most reported events involved verbal abuse (68%), followed by physical abuse (26%), outside confrontation (17%), and stalking (5%). By far, the most common perpetrators of violence against healthcare workers were bystanders including patient family members or other accompanying individuals. Notably, reporting was limited, with most cases conveyed to ED or hospital administration.

Conclusion

These results underscore the prevalence of WPV among Indian ED healthcare providers. High rates of verbal abuse followed by physical abuse are of concern. Most perpetrators of WPV against healthcare providers in this study were patient family members or bystanders rather than the patients themselves. It is imperative to prioritize implementing prevention strategies to create safer work environments for healthcare workers.
Development of pre-implantation genetic testing protocol for monogenic disorders (PGT-M) of Hb H disease
Authors: Somboonchai Pannarai , Charoenkwan Pimlak , Piyamongkol Sirivipa , Lattiwongsakorn Worashorn , Pantasri Tawiwan , Piyamongkol Wirawit
Published: July 2024

Hb H disease is the most severe form of α-thalassemia compatible with post-natal life. Compound heterozygous α0-thalassemia− SEA deletion/α+-thalassemia− 3.7kb deletion is the commonest cause of Hb H disease in Thailand. Preimplantation genetics testing for monogenic disorders (PGT-M) is an alternative for couples at risk of the disorder to begin a pregnancy with a healthy baby. This study aims to develop a novel PCR protocol for PGT-M of Hb H disease− SEA/−3.7kb using multiplex fluorescent PCR. A novel set of primers for α+-thalassemia− 3.7kb deletion was developed and tested. The PCR protocol for α0-thalassemia− SEA deletion was combined for Hb H disease− SEA/−3.7kb genotyping. The PCR protocols were applied to genomic DNA extracted from subjects with different thalassemia genotypes and on whole genome amplification (WGA) products from clinical PGT-M cycles of the families at risk of Hb Bart’s. The results were compared and discussed. The results showed three PCR products from α+-thalassemia− 3.7kb primer set, and three from α0thalassemiaSEA primer set. The results were consistent with the known thalassemia genotypes. The novel -α3.7 primers protocol was also tested on 37 WGA products from clinical PGT-M cycles giving accurate genotyping results and a satisfying amplification efficiency with the ADO rates of 2.7%, 0%, and 0% for HBA2, HBA1, and internal control fragments, respectively. This novel PCR protocol can precisely distinguish Hb H disease− SEA/−3.7kb from other genotypes. Additionally, this is the first PCR protocol for Hb H disease− SEA/−3.7kb which is optimal for PGT-M.
Screening for frailty and its association with activities of daily living, cognitive impairment, and falls among community-dwelling older adults in China
Authors: Ji Dakang , Guo Haijian , Qiu Shanhu , Dong Lirong , Shen Ya , Shen Zhengkai , Xu Jinshui
Published: July 2024

Objectives

Frailty is a prevalent geriatric condition that significantly impacts the health of older adults. This study aimed to examine the prevalence of frailty among older Chinese adults aged ≥ 65 years and to assess its association with adverse geriatric outcomes.

Method

This study included 20,724 older adults aged ≥ 65 years in Jiangsu Province, China, utilizing a random, stratified, multistage cluster sampling approach. Frailty was assessed using the 5-item FRAIL scale. Geriatric outcomes, such as independence in activities of daily living (ADL), cognitive impairment, and frequent fall events (occurring four or more times in the preceding year), were evaluated. Logistic regression models were employed to evaluate the association between frailty and geriatric outcomes, with results presented as odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The mean age of the participants was 73.4 ± 6.4 years. The standardized prevalence of prefrailty and frailty was 35.2% and 10.3%, respectively. Individuals identified as prefrail or frail tended to live in rural areas, have lower educational levels, be widowed, have lower incomes, and engage in less physical activity. Prefrailty and frailty were associated with an increased risk of limitations in BADL (OR: 9.62, 95% CI: 7.43–12.46; and OR: 29.25, 95% CI: 22.42–38.17, respectively) and IADL (OR: 2.54, 95% CI 2.35–2.74; and OR: 5.19, 95% CI 4.66–5.78, respectively), positive cognitive impairment screening (OR: 1.23, 95% CI: 1.16–1.31; and OR: 1.72, 95% CI: 1.56–1.91, respectively), and frequent falls (occurring four or more times in the preceding year) (OR: 3.38, 95% CI: 2.50–4.56; and OR: 8.37, 95% CI: 6.01–11.65). The association between frailty and both limitations in BADL and falls was notably more pronounced among the younger age groups (p for interaction < 0.001).

Conclusions

According to the 5-item FRAIL scale, frailty was associated with limitations in BADLs and IADLs, positive cognitive impairment screening, and recent falls among older adults living in the community. Screening for frailty in younger age groups has the potential to prevent declines in physical function and falls.
The use of technology by seniors with neurocognitive disorders in long-term care: a scoping review
Authors: Hardy Marie-Soleil , Fanaki Chaimaa , Savoie Camille
Published: July 2024

Background

To map the current state of knowledge about the use of technology with seniors with neurocognitive disorders in long-term care to foster interactions, wellness, and stimulation.

Methods

Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus); MEDLINE; PsycINFO; Embase and Web of Science were searched in eligible literature, with no limit of time, to describe the current use of technology by seniors with neurocognitive disorders in long-term care. All types of literature were considered except for theses, editorial, social media. This scoping review was built around the recommendations of Peters et al. (2020 version). Three researchers collaborated on the selection of articles and independently reviewed the papers, based on the eligibility criteria and review questions.

Results

The search yielded 3,605 studies, of which 39 were included. Most technology type reported was robotics. Included studies reports different positive effects on the use of such technology such as increase of engagement and positive.

Conclusion

The study highlights different types and potential benefits of technology for long-term care residents with neurocognitive disorders, emphasizing the crucial need for additional research to refine interventions and their use.
Association of frailty with workplace social activity, physical activity, and well-being among older employees: a moderated mediation in two income-variant samples
Authors: Danquah Emelia , Asiamah Nestor , Jnr Reginald Arthur-Mensah , Kouveliotis Kyriakos
Published: July 2024

Background

Research suggests that frailty is associated with lower physical activity and well-being in old age, but social activities at work may facilitate physical activity and its positive effect on well-being among older employees with frailty. This study, therefore, ascertained whether there is a moderated mediation of the association of frailty, Workplace Social Activity (WSA), and well-being by Physical Activity (PA).

Methods

The study adopted a cross-sectional design with relevant sensitivity analyses for confounding. The participants were within two Ghanaian samples with different income levels (low-income, n = 897, and higher income, n = 530). The minimum samples were calculated, and the statistical models were tested with Haye’s Process Model through structural equation modelling.

Results

Frailty was negatively associated with PA, and this relationship was moderated by WSA in both samples. Higher frailty was directly and indirectly associated with lower well-being in the higher-income sample but only indirectly associated with lower well-being in the low-income sample. The mediation of PA in the frailty-well-being relationship is partial in the higher-income sample but complete in the low-income sample. There was evidence of moderated mediation in both samples.

Conclusion

WSA may reduce the strength of the negative association of frailty with PA and well-being among older employees in both samples. Workplace interventions aimed at enhancing WSA may encourage PA and enhance well-being among older employees with frailty.
Predictors for the development of motoric cognitive risk syndrome in older adults
Authors: Rivan Nurul Fatin Malek , Ludin Arimi Fitri Mat , Clark Brian C. , Shahar Suzana
Published: July 2024

Background

Motoric cognitive risk (MCR) syndrome refers to a condition where both slow gait and memory complaints coexist, which heightens their vulnerability to developing dementia. Considering that the risk factors of MCR are elucidated from cross-sectional studies and also likely vary based on socioeconomic status, we conducted a community-based longitudinal study to determine the predictors of MCR among older adults in Malaysia.

Methods

Out of 1,249 older participants (aged 60 years and above) without MCR at baseline (Wave II of LRGS-TUA cohort study), 719 were successfully followed up after 3.5 years to identify predictors of subsequent MCR development. A comprehensive interview-based questionnaire was administered for sociodemographic information, cognitive function, psychosocial, functional status, and dietary intake. Anthropometric measurements, body composition, and physical performance were assessed. Univariate analyses were performed for each variable, followed by a hierarchical logistic regression analysis to identify the predictors of MCR that accounted for confounding effects between the studied factors.

Results

The incidence rate of MCR was 4.0 per 100 person-years. Smoking (Adjusted Odd Ratio (Adj OR) = 1.782; 95% Confidence Interval (CI):1.050–3.024), hypertension (Adj OR = 1.725; 95% CI:1.094–2.721), decreased verbal memory as assessed by the lower Rey Auditory Verbal Learning Test (RAVLT) (Adj OR = 1.891; 95% CI:1.103–3.243), and decreased functional status measured using instrumental activity of daily living (IADL) (Adj OR = 4.710; 95% CI:1.319–16.823), were predictors for MCR incidence.

Conclusions

Our study results provide an initial reference for future studies to formulate effective preventive management and intervention strategies to reduce the growing burden of adverse health outcomes, particularly among Asian older adults.
Mediastinal hematoma after trans-radial cerebral angiography: a case report
Authors: Ma Peipei , Gong Zhenyu , Du Meng , Zhu Deyuan , Li Peng , Fang Yibin
Published: July 2024

Background

Trans-radial (TRA) access has become increasingly prevalent in neurointervention. Nonetheless, mediastinal hematoma after TRA is an infrequent yet grave complication associated with a notably elevated mortality rate. While our review found no reported mediastinal hematoma cases managed conservatively within neuro-interventional literature, similar complications are documented in cardiac and vascular interventional radiology, indicating its potential occurrence across disciplines.

Case Presentation

Carotid computed tomography angiography (CTA) showed calcified plaques with stenosis (Left: Severe, Right: Moderate) in the bilateral internal carotid arteries (ICAs) of an 81-year-old male presented with paroxysmal weakness in the right upper limb. Dual antiplatelet therapy with aspirin and clopidogrel was administered. On day 7, DSA of the bilateral ICAs was performed via TRA. Post-DSA, the patient experienced transient loss of consciousness, chest tightness, and other symptoms without ECG or MRI abnormalities. Hemoglobin level decreased from 110 g/L to 92 g/L. Iodinated contrast-induced laryngeal edema was suspected, and the patient was treated with intravenous methylprednisolone. Neck CT indicated a possible mediastinal hemorrhage, which chest CTA confirmed. The patient’s treatment plan involved discontinuing antiplatelet medication as a precautionary measure against the potential occurrence of an ischemic stroke instead of the utilization of a covered stent graft and surgical intervention. Serial CTs revealed hematoma absorption. Discharge CT showed a reduced hematoma volume of 35 × 45 mm.

Conclusions

This case underscores the need for timely identification and precise manipulation of guidewires and guide-catheters through trans-radial access. The critical components of successful neuro-interventional techniques include timely examination, rapid identification, proper therapy, and diligent monitoring.
Designing a core data set for benign hysterectomy registration system and its implementation in a referral teaching hospital in Northwest Iran
Authors: Asl Fatemeh Moghadami , Maserat Elham , Vaezi Maryam , Mohammadzadeh Zeinab
Published: July 2024

Background and aims

Although minimally invasive hysterectomy offers advantages, abdominal hysterectomy remains the predominant surgical method. Creating a standardized dataset and establishing a hysterectomy registry system present opportunities for early interventions in reducing volume and selecting benign hysterectomy methods. This research aims to develop a dataset for designing benign hysterectomy registration system.

Methods

Between April and September 2020, a qualitative study was carried out to create a data set for enrolling patients who were candidate for hysterectomy. At this stage, the research team conducted an information needs assessment, relevant data element identification, registry software development, and field testing; Subsequently, a web-based application was designed. In June 2023the registry software was evaluated using data extracted from medical records of patients admitted at Al-Zahra Hospital in Tabriz, Iran.

Results

During two months, 40 patients with benign hysterectomy were successfully registered. The final dataset for the hysterectomy patient registry comprise 11 main groups, 27 subclasses, and a total of 91 Data elements. Mandatory data and essential reports were defined. Furthermore, a web-based registry system designed and evaluated based on data set and various scenarios.

Conclusion

Creating a hysterectomy registration system is the initial stride toward identifying and registering hysterectomy candidate patients. this system capture information about the procedure techniques, and associated complications. In Iran, this registry can serve as a valuable resource for assessing the quality of care delivered and the distribution of clinical measures.