bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual linguistic statistical learning is traceable through neural entrainment
Authors: Sáringer Szabolcs , Kaposvári Péter , Benyhe András
Published: March 2024

The human brain can detect statistical regularities in the environment across a wide variety of contexts. The importance of this process is well‐established not just in language acquisition but across different modalities; in addition, several neural correlates of statistical learning have been identified. A current technique for tracking the emergence of regularity learning and localizing its neural background is frequency tagging (FT). FT can detect neural entrainment not only to the frequency of stimulus presentation but also to that of a hidden structure. Auditory learning paradigms with linguistic and nonlinguistic stimuli, along with a visual paradigm using nonlinguistic stimuli, have already been tested with FT. To complete the picture, we conducted an FT experiment using written syllables as stimuli and a hidden triplet structure. Both behavioral and neural entrainment data showed evidence of structure learning. In addition, we localized two electrode clusters related to the process, which spread across the frontal and parieto‐occipital areas, similar to previous findings. Accordingly, we conclude that fast‐paced visual linguistic regularities can be acquired and are traceable through neural entrainment. In comparison with the literature, our findings support the view that statistical learning involves a domain‐general network.
Psychosocial experiences of competitive rugby players on the “long, long journey” to recovery following ACL ruptures and reconstruction
Authors: Borman Anel , Derman Wayne , Grobbelaar Heinrich
Published: March 2024

Anterior Cruciate Ligament (ACL) injuries are serious and potentially career‐ending. Reconstruction surgery and extended rehabilitation typically follow, but some athletes never attain the same level of sport performance. The psychosocial experiences of athletes who sustain ACL injuries and their cognitive appraisal, emotional and behavioral responses to the injury, and reconstruction require further attention during the different recovery phases. The aim is to explore these psychosocial experiences, social support needs and sources thereof of competitive athletes who sustained unilateral ACL ruptures and underwent reconstruction surgery. Semi‐structured interviews with six competitive rugby players (M age: 22.3 ± 2.92 years), elicited information at seven time‐points. We analyzed the qualitative information through thematic analysis. Five common themes emerged: (1) cognitive appraisal, (2) emotional responses (negative and positive affective responses), (3) behavioral responses, (4) social support needs and sources thereof, and (5) adversity‐induced identity expansion (athletic and person‐centered identities). In‐vivo quotes gave a rich description of the athletes' experiences throughout the “long, long journey” to return‐to‐sport. These findings may sensitize and assist sports healthcare professionals, coaches, teammates, family, and friends to explore various psychosocial experiences throughout the injury and recovery period. Phase‐appropriate psychosocial support or referral to sport psychology services is recommended to enhance the recovery process, improve long‐term physical and mental health, and subsequent performance.
C. S. Peirce on Jeremy Bentham: “A shallow logician” confined to analysis of “lower motives”
Authors: Zhang Yanxiang
Published: March 2024

C.S. Peirce offered an evaluation of Bentham's philosophy to the effect that on some points Bentham's performance was of great value, but essentially, he was ‘a shallow logician’ confined to analysis of ‘lower motive’. This paper argues that Bentham's logic is deeply metaphysically based, multi‐levelled, and comprehensive. There are at least three constituent parts in his utilitarian logic: the first is his ontology, with its distinction between real and fictitious entities, and with pain and pleasure constituting the core real entities; the second is his reductionism in, and analytical view of, simple and complex pleasures and pains; the third is the distinction between private ethics and public ethics. Bentham's logic is staunchly based on empiricism and truth and he developed a pragmatic utilitarian solution to overcome the potential impasse of Hume's scepticism through a mechanism of reflection. Even the doctrines of belief and abduction embraced and developed by Peirce are contained in Bentham's utilitarian logic. Bentham would certainly take Peirce's philosophy as ipse dixitism. Peirce was not in fact a serious reader of Bentham and failed to employ the distinction between argument and argumentation in his study of Bentham's logic.
IbNF‐YA1 is a key factor in the storage root development of sweet potato
Authors: Xue Luyao , Wang Yuxin , Fan Yue , Jiang Zhicheng , Wei Zihao , Zhai Hong , He Shaozhen , Zhang Huan , Yang Yufeng , Zhao Ning , Gao Shaopei , Liu Qingchang
Published: March 2024

As a major worldwide root crop, the mechanism underlying storage root yield formation has always been a hot topic in sweet potato [Ipomoea batatas (L.) Lam.]. Previously, we conducted the transcriptome database of differentially expressed genes between the cultivated sweet potato cultivar “Xushu18,” its diploid wild relative Ipomoea triloba without storage root, and their interspecific somatic hybrid XT1 with medium‐sized storage root. We selected one of these candidate genes, IbNF‐YA1, for subsequent analysis. IbNF‐YA1 encodes a nuclear transcription factor Y subunit alpha (NF‐YA) gene, which is significantly induced by the natural auxin indole‐3‐acetic acid (IAA). The storage root yield of the IbNF‐YA1 overexpression (OE) plant decreased by 29.15–40.22% compared with the wild type, while that of the RNAi plant increased by 10.16–21.58%. Additionally, IAA content increased significantly in OE plants. Conversely, the content of IAA decreased significantly in RNAi plants. Furthermore, real‐time quantitative reverse transcription‐PCR (qRT‐PCR) analysis demonstrated that the expressions of the key genes IbYUCCA2, IbYUCCA4, and IbYUCCA8 in the IAA biosynthetic pathway were significantly changed in transgenic plants. The results indicated that IbNF‐YA1 could directly target IbYUCCA4 and activate IbYUCCA4 transcription. The IAA content of IbYUCCA4 OE plants increased by 71.77–98.31%. Correspondingly, the storage root yield of the IbYUCCA4 OE plant decreased by 77.91–80.52%. These findings indicate that downregulating the IbNF‐YA1 gene could improve the storage root yield in sweet potato.
Computed tomographic features of canine intracranial and jugular foraminal masses involving the combined glossopharyngeal, vagus, and accessory nerve roots
Authors: Lluesma Begoña , Whitley Nathaniel T. , Hughes Jonathan R.
Published: March 2024

A chronic cough, gag, or retch is a common presenting clinical complaint in dogs. Those refractory to conservative management frequently undergo further diagnostic tests to investigate the cause, including CT examination of their head, neck, and thorax for detailed morphological assessment of their respiratory and upper gastrointestinal tract. This case series describes five patients with CT characteristics consistent with an intracranial and jugular foraminal mass of the combined glossopharyngeal (IX), vagus (X), and accessory (XI) cranial nerves and secondary features consistent with their paresis. The consistent primary CT characteristics included an intracranial, extra‐axial, cerebellomedullary angle, and jugular foraminal soft tissue attenuating, strongly enhancing mass (5/5). Secondary characteristics included smooth widening of the bony jugular foramen (5/5), mild hyperostosis of the petrous temporal bone (3/5), isolated severe atrophy of the ipsilateral sternocephalic, cleidocephalic, and trapezius muscles (5/5), atrophy of the ipsilateral thyroarytenoideus and cricoarytenoideus muscles of the vocal fold (5/5), and an ipsilateral “dropped” shoulder (4/5). Positional variation of the patient in CT under general anesthesia made the “dropped” shoulder of equivocal significance. The reported clinical signs and secondary CT features reflect a unilateral paresis of the combined cranial nerves (IX, X, and XI) and are consistent with jugular foramen syndrome/Vernet's syndrome reported in humans. The authors believe this condition is likely chronically underdiagnosed without CT examination, and this case series should enable earlier CT diagnosis in future cases.
Commuting tuple of multiplication operators homogeneous under the unitary group
Authors: Ghara Soumitra , Kumar Surjit , Misra Gadadhar , Pramanick Paramita
Published: March 2024

Let be the group of unitary matrices. We find conditions to ensure that a ‐homogeneous ‐tuple is unitarily equivalent to multiplication by the coordinate functions on some reproducing kernel Hilbert space , . We describe this class of ‐homogeneous operators, equivalently, nonnegative kernels quasi‐invariant under the action of . We classify quasi‐invariant kernels transforming under with two specific choice of multipliers. A crucial ingredient of the proof is that the group has exactly two inequivalent irreducible unitary representations of dimension and none in dimensions , . We obtain explicit criterion for boundedness, reducibility, and mutual unitary equivalence among these operators.
Comparison of three titanium-precursors for atomic-layer-deposited TiO2 for passivating contacts on silicon
Authors: Hiller Daniel , Munnik Frans , López-Vidrier Julian , Solonenko Dmytro , Reif Johanna , Knaut Martin , Thimm Oliver , Grant Nicholas E.
Published: March 2024

Atomic layer-deposited (ALD) TiO2 thin films on silicon were deposited using titanium tetrachloride (TiCl4), titanium tetraisopropoxide (TTIP), and tetrakis(dimethylamino)titanium (TDMAT) together with water vapor as the oxidant at temperatures ranging between 75 and 250 °C. The Si surface passivation quality of as-deposited and isothermally annealed samples was compared using photoconductance lifetime measurements in order to calculate their effective surface recombination velocities Seff. A low Seff of 3.9 cm/s (J0s=24fA/cm2) is achieved for as-deposited TiCl4-TiO2 at 75 °C when a chemically grown (i.e., from RCA cleaning) SiOx interface layer is present. Depositing TTIP-TiO2 at 200 °C on a chemically grown SiOx interface layer yields equivalent Seff values; however, in this case, TTIP-TiO2 requires a 5–15 min postdeposition forming gas anneal at 250 °C. In contrast, TDMAT-TiO2 was not found to provide a similar level of passivation with/without a chemically grown SiOx interface layer and postdeposition anneal. Modeling of the effective lifetime curves was used to determine the magnitude of the effective charge densities Qf in the TiO2 films. In all cases, Qf was found to be of the order of ∼1011 q cm−2, meaning field-effect passivation arising from ALD TiO2 is relatively weak. By comparing the material properties of the various TiO2 films using ellipsometry, photothermal deflection spectroscopy, Raman spectroscopy, elastic recoil detection analysis, x-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy, we find experimental support for the role of Cl (in conjunction with hydrogen) playing a beneficial role in passivating dangling bond defects at the Si surface. It is concluded that low deposition temperature TiCl4 processes are advantageous, by providing the lowest Seff without any postanneal and a comparatively high growth per cycle (GPC).
Fine tuning of Nb-incorporated TiO2 thin films by atomic layer deposition and application as efficient electron transport layer in perovskite solar cells
Authors: Vincent Thomas , Coutancier Damien , Dally Pia , Al Katrib Mirella , Frégnaux Mathieu , Cacovich Stefania , Donsanti Frédérique , Yaïche Armelle , Medjoubi Karim , Guillemot Thomas , Provost Marion , Rousset Jean , Bouttemy Muriel , Schneider Nathanaelle
Published: March 2024

Access to finely tuned thin films that can act as electron transport layer (ETL) and adapt to the absorber composition and whole cell fabrication process is key to achieve efficient perovskite-based solar cells. In this study, the growth of mixed niobium-titanium oxide (Nb-TiO2) thin films by atomic layer deposition and its use to extract photogenerated electrons is reported. Films were obtained at 200 °C from titanium (IV) i-propoxide, (t-butylimido)tris(diethylamido)niobium(V), and water by introducing Nb2O5 growth cycle in a TiO2 matrix. Process parameters (order of precursor introduction, cycle ratio) were optimized; the growth mechanism and the effective Nb incorporation were investigated by an in situ quartz crystal microbalance and x-ray photoelectron spectroscopy. The composition, morphology, structural, and optoelectronic properties of the as-deposited films were determined using a variety of characterization techniques. As a result, a fine control of the film properties (between TiO2 and Nb2O5 ones) could be achieved by tuning Nb content. To allow a successful implementation in solar devices, a comprehensive annealing study under several conditions (temperatures, various atmospheres) was conducted leading to an evolution of the optical properties due to a morphological change. Ultimately, the incorporation of these 15 nm-thick films in mesoscopic perovskite solar cells as ETL shows an improvement of the cell performances and of their stability with increasing Nb content, in comparison of both TiO2 and Nb2O5 pure compounds, reaching power conversion efficiency up to 18.3% and a stability above 80% of its nominal value after 138 h under illumination.
Extra centrosomes delay DNA damage–driven tumorigenesis
Authors: Braun Vincent Z. , Karbon Gerlinde , Schuler Fabian , Schapfl Marina A. , Weiss Johannes G. , Petermann Paul Y. , Spierings Diana C.J. , Tijhuis Andrea E. , Foijer Floris , Labi Verena , Villunger Andreas
Published: March 2024

Deregulated centrosome numbers are frequently found in human cancer and can promote malignancies in model organisms. Current research aims to clarify if extra centrosomes are cause or consequence of malignant transformation, and if their biogenesis can be targeted for therapy. Here, we show that oncogene-driven blood cancer is inert to genetic manipulation of centrosome numbers, whereas the formation of DNA damage–induced malignancies is delayed. We provide first evidence that this unexpected phenomenon is connected to extra centrosomes eliciting a pro-death signal engaging the apoptotic machinery. Apoptosis induction requires the PIDDosome multi-protein complex, as it can be abrogated by loss of any of its three components,
Caspase-2
,
Raidd/Cradd
, or
Pidd1
. BCL2 overexpression equally blocks cell death, documenting for the first time induction of mitochondrial apoptosis downstream of extra centrosomes. Our findings demonstrate context-dependent effects of centrosome amplification during transformation and ask to adjust current belief that extra centrosomes are intrinsically pro-tumorigenic.
Lithium isotopic constraints on the evolution of continental clay mineral factory and marine oxygenation in the earliest Paleozoic Era
Authors: Wei Guang-Yi , Zhao Mingyu , Sperling Erik A. , Gaines Robert R. , Kalderon-Asael Boriana , Shen Jun , Li Chao , Zhang Feifei , Li Gaojun , Zhou Chuanming , Cai Chunfang , Chen Daizhao , Xiao Ke-Qing , Jiang Lei , Ling Hong-Fei , Planavsky Noah J. , Tarhan Lidya G.
Published: March 2024

The evolution of oxygen cycles on Earth’s surface has been regulated by the balance between molecular oxygen production and consumption. The Neoproterozoic–Paleozoic transition likely marks the second rise in atmospheric and oceanic oxygen levels, widely attributed to enhanced burial of organic carbon. However, it remains disputed how marine organic carbon production and burial respond to global environmental changes and whether these feedbacks trigger global oxygenation during this interval. Here, we report a large lithium isotopic and elemental dataset from marine mudstones spanning the upper Neoproterozoic to middle Cambrian [~660 million years ago (Ma) to 500 Ma]. These data indicate a dramatic increase in continental clay formation after ~525 Ma, likely linked to secular changes in global climate and compositions of the continental crust. Using a global biogeochemical model, we suggest that intensified continental weathering and clay delivery to the oceans could have notably increased the burial efficiency of organic carbon and facilitated greater oxygen accumulation in the earliest Paleozoic oceans.
Subaerial volcanism broke mid-Proterozoic environmental stasis
Authors: Zhang Shuichang , Wang Huajian , Wang Xiaomei , Zheng Wang , Hao Jihua , Pogge von Strandmann Philip A. E. , Ye Yuntao , Shi Miao , Liu Yuke , Lyu Yitong
Published: March 2024

The mid-Proterozoic, spanning 1.8 to 0.8 billion years ago, is recognized as a phase of marine anoxia, low marine primary productivity (MPP), and constrained eukaryotic biodiversity. However, emerging evidence suggesting intermittent environmental disturbances and concurrent eukaryotic evolution challenges the notion of a stagnant Earth during this era. We present a study detailing volcanic activity and its consequential impact on terrestrial weathering and MPP, elucidated through the examination of 1.4-billion-year-old tropical offshore sediments. Our investigation, leveraging precise mercury (Hg) and lithium (Li) isotopic analyses, reveals the introduction of fresh rock substrates by local volcanism. This geological event initiated a transformative process, shifting the initial regolith-dominated condition in tropical lowland to a regime of enhanced chemical weathering and denudation efficiency. Notably, the heightened influx of nutrient-rich volcanic derivatives, especially phosphorus, spurred MPP rates and heightened organic carbon burial. These factors emerge as potential drivers in breaking the long-term static state of the mid-Proterozoic.
Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism
Authors: Chi Ximin , Chen Yiming , Li Yaning , Dai Lu , Zhang Yuanyuan , Shen Yaping , Chen Yun , Shi Tianhao , Yang Haonan , Wang Zilong , Yan Renhong
Published: March 2024

The solute carrier 13 (SLC13) family comprises electrogenic sodium ion–coupled anion cotransporters, segregating into sodium ion–sulfate cotransporters (NaSs) and sodium ion–di- and–tricarboxylate cotransporters (NaDCs). NaS1 and NaDC1 regulate sulfate homeostasis and oxidative metabolism, respectively. NaS1 deficiency affects murine growth and fertility, while NaDC1 affects urinary citrate and calcium nephrolithiasis. Despite their importance, the mechanisms of substrate recognition and transport remain insufficiently characterized. In this study, we determined the cryo–electron microscopy structures of human NaS1, capturing inward-facing and combined inward-facing/outward-facing conformations within a dimer both in apo and sulfate-bound states. In addition, we elucidated NaDC1’s outward-facing conformation, encompassing apo, citrate-bound, and
N
-(
p
-amylcinnamoyl) anthranilic acid (ACA) inhibitor–bound states. Structural scrutiny illuminates a detailed elevator mechanism driving conformational changes. Notably, the ACA inhibitor unexpectedly binds primarily anchored by transmembrane 2 (TM2), Loop 10, TM11, and TM6a proximate to the cytosolic membrane. Our findings provide crucial insights into SLC13 transport mechanisms, paving the way for future drug design.
MoS2phononic crystals for advanced thermal management
Authors: Xiao Peng , El Sachat Alexandros , Angel Emigdio Chávez , Ng Ryan C. , Nikoulis Giorgos , Kioseoglou Joseph , Termentzidis Konstantinos , Sotomayor Torres Clivia M. , Sledzinska Marianna
Published: March 2024

Effective thermal management of electronic devices encounters substantial challenges owing to the notable power densities involved. Here, we propose layered MoS2phononic crystals (PnCs) that can effectively reduce thermal conductivity (κ) with relatively small disruption of electrical conductivity (σ), offering a potential thermal management solution for nanoelectronics. These layered PnCs exhibit remarkable efficiency in reducing κ, surpassing that of Si and SiC PnCs with similar periodicity by ~100-fold. Specifically, in suspended MoS2PnCs, we measure an exceptionally low κ down to 0.1 watts per meter kelvin, below the amorphous limit while preserving the crystalline structure. These findings are supported by molecular dynamics simulations that account for the film thickness, porosity, and temperature. We demonstrate the approach efficiency by fabricating suspended heat-routing structures that effectively confine and guide heat flow in prespecified directions. This study underpins the immense potential of layered materials as directional heat spreaders, thermal insulators, and active components for thermoelectric devices.
Scedosporiosis and lomentosporiosis: modern perspectives on these difficult-to-treat rare mold infections
Authors: Neoh Chin Fen , Chen Sharon C-A , Lanternier Fanny , Tio Shio Yen , Halliday Catriona L. , Kidd Sarah E. , Kong David C. M. , Meyer Wieland , Hoenigl Martin , Slavin Monica A.
Published: March 2024

AlthoughScedosporiumspecies andLomentospora prolificansare uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the differentScedosporiumspecies.L. prolificansis intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.
Retracted and republished from: “The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs”
Authors: Li Yanbai , Huo Shanshan , Yin Zhe , Tian Zuguang , Huang Fang , Liu Peng , Liu Yue , Yu Fei
Published: March 2024

Influenza viruses (IVs) threaten global human health due to the high morbidity, infection, and mortality rates. Currently, the influenza drugs recommended by the Food and Drug Administration are oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These recommended antivirals are currently effective for major subtypes of IVs as the compounds target conserved domains in neuraminidase or polymerase acidic (PA) protein. However, this trend may gradually change due to the selection of antiviral drugs and the natural evolution of IVs. Therefore, there is an urgent need to develop drugs related to the treatment of influenza to deal with the next pandemic. Here, we summarized the cutting-edge research in mechanism of action, inhibitory activity, and clinical efficacy of drugs that have been approved and drugs that are still in clinical trials for influenza treatment. We hope this review will provide up-to-date and comprehensive information on influenza antivirals and generate hypotheses for screens and development of new broad-spectrum influenza drugs in the near future.
Structural analysis of resistance-nodulation cell division transporters
Authors: Klenotic Philip A. , Yu Edward W.
Published: March 2024

Infectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.
Modelling the potential clinical and economic impact of universal antenatal hepatitis C (HCV) screening and providing treatment for pregnant women with HCV and their infants in Egypt: a cost-effectiveness study
Authors: Hachicha-Maalej Nadia , Lepers Clotilde , Collins Intira Jeannie , Mostafa Aya , Ades Anthony E , Judd Ali , Scott Karen , Gibb Diana M , Pett Sarah , Indolfi Giuseppe , Yazdanpanah Yazdan , El Sayed Manal H , Deuffic-Burban Sylvie
Published: March 2024

Backgrounds and aims

Pregnant women and children are not included in Egypt’s hepatitis C virus (HCV) elimination programmes. This study assesses the cost-effectiveness of several screening and treatment strategies for pregnant women and infants in Egypt.

Design

A Markov model was developed to simulate the cascade of care and HCV disease progression among pregnant women and their infants according to different screening and treatment strategies, which included: targeted versus universal antenatal screening; treatment of women in pregnancy or deferred till after breast feeding; treatment of infected children at 3 years vs 12 years. Current practice is targeted antenatal screening with deferred treatment for the mother and child. We also explored prophylactic treatment after birth for children of diagnosed HCV-infected women. Discounted lifetime cost, life expectancy (LE) and disability-adjusted life-years (DALYs) were calculated separately for women and their infants, and then combined.

Results

Current practice led to the highest cost (US$314.0), the lowest LE (46.3348 years) and the highest DALYs (0.0512 years) per mother–child pair. Universal screening and treatment during pregnancy followed by treatment of children at 3 years would be less expensive and more effective (cost saving) compared with current practice (US$219.3, 46.3525 and 0.0359 years). Prophylactic treatment at birth for infants born to HCV RNA-positive mothers would also be similarly cost saving, even with treatment uptake as low as 15% (US$218.6, 46.3525 and 0.0359 years). Findings were robust to reasonable changes in parameters.

Conclusion

Universal screening and treatment of HCV in pregnancy, with treatment of infected infants at age 3 years is cost saving compared with current practice in the Egyptian setting.
Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review
Authors: Villard Christina , Jorns Carl , Bergquist Annika
Published: March 2024

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterised by persistent biliary inflammation resulting in fibrosis and multifocal strictures of the biliary tree. The course of disease is highly variable, ranging from asymptomatic disease to the development of end-stage biliary cirrhosis and an increased risk of biliary tract cancer (BTC), particularly cholangiocarcinoma (CCA).

PSC is the most important risk factor for CCA in younger people, with a reported lifetime prevalence ranging from 6% to 13%. Perihilar CCA (pCCA), involving the hepatic duct bifurcation, is the most common CCA amounting to approximately 50% of all cases, whereas intrahepatic CCA (iCCA), located within the hepatic parenchyma, represents less than 10%.

CCA is an aggressive tumour, and only a minority of patients are amenable to surgical resection with curative intent. Radical liver resection and liver transplantation are potentially curative therapeutic options in patients with PSC in the absence of metastatic or locally advanced disease. Liver transplantation with neoadjuvant chemoradiation could be considered in selected patients with unresectable pCCA and without pretreatment in patients with PSC with bile duct high-grade dysplasia. Recent reports demonstrating favourable outcomes in transplanted patients with small iCCA and patients with locally advanced disease following neoadjuvant therapy have challenged the previously described poor outcome in transplanted patients with iCCA.

Treatment for CCA is challenged by the inherent difficulties in enabling an early diagnosis and thereby preventing an otherwise dismal prognosis. This comprehensive review aims to describe therapeutic considerations and challenges in patients with PSC-CCA.
National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett’s oesophagus and stage I oesophageal adenocarcinoma
Authors: di Pietro Massimiliano , Trudgill Nigel J , Vasileiou Melina , Longcroft-Wheaton Gaius , Phillips Alexander W , Gossage James , Kaye Philip V , Foley Kieran G , Crosby Tom , Nelson Sophie , Griffiths Helen , Rahman Muksitur , Ritchie Gill , Crisp Amy , Deed Stephen , Primrose John N
Published: March 2024

Barrett’s oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett’s oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett’s oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett’s oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett’s-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett’s oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.
IoT Based Wireless Communication System for Smart Irrigation and Rice Leaf Disease Prediction Using ResNeXt-50
Authors: Sangeetha S. , Indumathi N. , Grover Reena , Singh Rakshit , Mavi Renu
Published: March 2024

Agriculture not only plays a vital role in human survival but also contributes to the nation’s greater economic development. With the use of technologies like IoT, WSNs, remote sensing, camera surveillance, and many more, precision agriculture is the newest buzzword in the field of technology. Its primary goal is to lessen the labour of farmers while increasing the output of farms. Many machine learning techniques are designed to improve the productivity and quality of the crops, but the improper irrigation and disease prediction of the existing techniques leads to loss of productivity and quality. Hence, the IoT based wireless communication system is designed for smart irrigation and rice leaf prediction using ANN and ResNeXt-50 model. In this designed model, smart irrigation is controlled by collecting the temperature and moisture of the soil in the agricultural field by using the WSN. Likewise, a surveillance camera is placed in the agricultural field to capture the rice leaf to find the disease such as rice blast, leaf smut, brown spot and bacterial blight. These collected data are processed and classified for smart irrigation and rice leaf disease prediction. For evaluating the performance of both the ANN and ResNeXt-50 trained model, the performance metrics such as accuracy, sensitivity, specificity, precision, error etc. The performance metrics for the ANN and ResNeXt-50 model are 0.9427, 0.925, 0.903, 0.86, 0.0573 and 0.967, 0.935, 0.943, 0.939 and 0.033. Thus, the evaluation of the designed model results that the proposed approach is performing better compared to the current techniques.
Curvature-mediated source and sink effects on the genesis of premature ventricular complexes in long QT syndrome
Authors: Zhang Yuhao , Zhang Zhaoyang , Qu Zhilin
Published: March 2024

The effects of the curvature or geometry of the repolarization gradient region and wavefront curvature on the genesis of premature ventricular complexes are systematically investigated using computer modeling and simulation. Premature ventricular complexes can be promoted by either positive or negative curvature of the gradient region depending on the source and sink conditions. The underlying mechanisms of the curvature effects are revealed, which provides mechanistic insights into arrhythmogenesis in cardiac diseases.
Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart
Authors: Guevara Amanda , Smith Charlotte E. R. , Caldwell Jessica L. , Ngo Lena , Mott Lilian R. , Lee I-Ju , Tapa Srinivas , Wang Zhen , Wang Lianguo , Woodward William R. , Ng G. Andre , Habecker Beth A. , Ripplinger Crystal M.
Published: March 2024

Here, we show that chronic nicotine exposure was associated with increased heart rate, increased susceptibility to alternans, and reduced sympathetic electrophysiological responses in the intact rabbit heart. We suggest that this was due to sympathetic hypoinnervation of the myocardium and diminished β-adrenergic responsiveness of the sinoatrial node following nicotine treatment. Though these differences did not result in increased arrhythmia propensity in our study, we hypothesize that prolonged nicotine exposure may exacerbate this proarrhythmic remodeling.
Ferroptosis Mediates Pulmonary Fibrosis: Implications for the Effect of Astragalus and Panax notoginseng Decoction
Authors: Wen Jing , Wang Cui , Song Li-yun , Wang Yin-ying , Liang Peng-tao , Pang Wen-lin , Yin Wen , Zhang Qiang , Zhao Wei-tian , Sun Xue-ping , Yan Jin-yuan , Yang Zhong-shan
Published: March 2024

Context. Ferroptosis is known to influence the pathogenesis of pulmonary fibrosis. Astragalus and Panax notoginseng are used to treat pulmonary fibrosis; however, the therapeutic mechanisms require further elucidation. Objective. To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods. First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor β, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results. APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.
Analysis and Simulation of Lateral Collision Risk under Paired Approach
Authors: Lu Fei , Zhang Jian , Chen Haonan , Chen Zichen
Published: March 2024

The paired approach can improve the efficiency of closely spaced parallel runways. Calculating the probability and frequency of horizontal overlap is an indispensable step when evaluating the horizontal collision risk of the paired approach. As the generation of horizontal overlap probability is closely related to horizontal position error, we propose a calculation method of horizontal overlap probability based on position error from the perspective of pilot operation. First, according to the principle of flight mechanics, the attitude adjustment model is established for the horizontal direction of the approach process, and the pilot’s operation model for various position errors is based on the concept of the stochastic process. This attitude adjustment model can replicates the process of the pilot operating the steering column to change the aircraft’s attitude. When combined with the pilot’s operation model, it is possible to simulate the position errors generated during the approach process. Building on this, the horizontal overlapping conditions of two aircraft are analyzed to simulate the horizontal overlap process in the paired approach. The duration and instances of overlap counted and the ratio between these results and the total running time give the overlap probability and frequency. Multiple simulations in MATLAB reveal that higher pilot operating accuracy shortens the time for the aircraft to align with the course, whereas lower accuracy leads to unstable horizontal position errors. Furthermore, the horizontal overlap in paired approaches primarily occurs at the beginning of the procedure, and enhancing the pilot’s operating accuracy does not significantly affect the probability and frequency of horizontal overlap.
Semicontinuous Blending of Pharmaceutical Ingredients and the Impact of Process Parameters on the Blending Performance of an Integrated Feeder Blender Operating Semicontinuously
Authors: Kumar Sumit , Huang Yan-Shu , Nagy Zoltan , Reklaitis Gintaras V. , Gonzalez Marcial , Mort Paul
Published: March 2024

The pharmaceutical industry is looking for new and innovative ways of manufacturing to improve product quality and reduce process complexity. In manufacturing oral solid dosage products, blending is a crucial step in ensuring the homogeneity of active pharmaceutical ingredients (APIs) in the final product. Currently, batch and continuous blending are the two commonly used modes for blending in the industry. However, these methods have limitations in terms of blending time, manual intervention, and flexibility in handling multiple ingredients. To address these limitations, this study aims to explore the feasibility and benefits of using a semicontinuous blending mode in the pharmaceutical industry. A case study is conducted using a binary blend of microcrystalline cellulose and acetaminophen to compare the performance of the semicontinuous mode of blending with the batch and continuous blending modes. The results show that the semicontinuous blending setup can produce blends with good blend uniformity and homogeneity and that the output can be used for both batch and continuous downstream operations. The effect of variation in the three most important process parameters, impeller rotation per minute, blending time, and fill level on the blend uniformity, is also investigated. The semicontinuous blending mode had a higher line rate of 12.5 kg/hour than a similarly sized batch blender at 3.6 kg/hour and less than that of a continuous blender. The benefits of the new blending mode include reduced blending time, minimal manual intervention, flexibility in blending multiple ingredients, easier scale-up, and a smaller footprint. Overall, this study highlights the relative advantages of using this new semicontinuous blending mode in pharmaceutical manufacturing and its potential as a good alternative to the existing blending modes. The semicontinuous mode is well placed between the batch blending and continuous blending mode, with many benefits over the former mode and performance comparable to the latter continuous mode.
Investigation on Quality Characteristics and Antidiabetic Properties of Mulberry Leaf Fu Brick Tea
Authors: Shao Yuanyuan , Lin Ling , Xu Wei , Gong Zhihua , Li Jinfeng , Zhang Jun , Yan Xinpei , Liu Zhonghua , Xiao Wenjun
Published: March 2024

Mulberry leaves (Morus alba L.) exhibit antidiabetic properties; however, their taste is unappetizing, leading to limited practical applications. Although Fu brick tea has a favorable flavor, its hypoglycemic effects are weak. Hence, we combined the two to create mulberry leaf Fu brick tea (SF) and investigated its sensory perception, safety, microorganism content, key metabolites, and impact on hyperglycemic mice using the same raw materials and techniques to prepare Fu brick tea (F) and mulberry leaf brick tea (S) individually. Our study showed that SF, which comprises blended mulberry leaf primary dark tea and primary dark tea (1 : 3 g/g), was sweeter and smoother, with a median lethal dose of 22.3 g/kg, indicating that it is safe for consumption. Compared to F, caffeine levels were reduced in SF and 1-deoxynojirimycin and aminobutyric acid levels were increased. Phenolic substances and flavonoids showed increased levels in SF compared with S. These changes contribute to the taste and functionality of SF. The primary microorganisms in SF were Bacillus, Lactobacillus, and Aspergillus, which contributed to the improved quality. SF demonstrated its antidiabetic effects by reducing the blood sugar levels of hyperglycemic mice, restoring the function of pancreatic cells, reducing lipid levels, and improving the antioxidant capacity of the liver. Overall, SF exhibited a better taste and antidiabetic properties than F and S, highlighting its potential as a functional beverage.
Cytokine Storm Syndrome Responsive to IL‐1 Inhibition in Trisomy 21
Authors: Magnarelli Aimee , Shalen Julia , Gutierrez Maria J.
Published: March 2024

Background. Cytokine storm syndromes (CSS) are life‐threatening systemic inflammatory disorders caused by immune system dysregulation. They can lead to organ failure and are triggered by various factors, including infections, malignancy, inborn errors of immunity, and autoimmune conditions. Trisomy 21 (TS21), also known as Down syndrome, is a genetic disorder associated with immune dysfunction, increased infection susceptibility, and inflammation. While TS21 has been linked to infectious‐triggered hyperinflammation, its role as a primary cause of CSS has not been confirmed. Case Presentation. We present a case of a 16‐year‐old male with TS21 with fever, rash, joint pain, and abdominal symptoms. Extensive investigations ruled out infections, autoimmune conditions, malignancies, and inborn errors of immunity as triggers for a CSS. The patient’s symptoms improved with treatment using IL‐1 inhibition and corticosteroids. Conclusions. This case reinforces that TS21 is an immune dysregulation disorder and highlights the importance of considering CSS in TS21 patients, even when triggers are unclear. The positive response to IL‐1 inhibition in this patient suggests that dysregulation of the IL‐1 superfamily and the NLRP3 inflammasome may contribute to CSS in TS21. This finding raises the possibility of using IL‐1 inhibition as a treatment approach for CSS in TS21 patients.
GD2-Targeting CAR T-cell Therapy for Patients with GD2+ Medulloblastoma
Authors: Ciccone Roselia , Quintarelli Concetta , Camera Antonio , Pezzella Michele , Caruso Simona , Manni Simona , Ottaviani Alessio , Guercio Marika , Del Bufalo Francesca , Quadraccia Maria Cecilia , Orlando Domenico , Di Cecca Stefano , Sinibaldi Matilde , Aurigemma Mariasole , Iaffaldano Laura , Sarcinelli Andrea , D'Amore Maria Luisa , Ceccarelli Manuela , Nazio Francesca , Marabitti Veronica , Giorda Ezio , Pezzullo Marco , De Stefanis Cristiano , Carai Andrea , Rossi Sabrina , Alaggio Rita , Del Baldo Giada , Becilli Marco , Mastronuzzi Angela , De Angelis Biagio , Locatelli Franco
Published: March 2024

Purpose:

Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard of care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, and endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward the disialoganglioside GD2 can represent a potentially more effective treatment with reduced long-term side effects.

Experimental Design:

GD2 expression was evaluated on primary tumor biopsies of MB children by flow cytometry. GD2 expression in MB cells was also evaluated in response to an EZH2 inhibitor (tazemetostat). In in vitro and in vivo models, GD2+ MB cells were targeted by a CAR-GD2.CD28.4-1BBζ (CAR.GD2)-T construct, including the suicide gene inducible caspase-9.

Results:

GD2 was expressed in 82.68% of MB tumors. The SHH and G3–G4 subtypes expressed the highest levels of GD2, whereas the WNT subtype expressed the lowest. In in vitro coculture assays, CAR.GD2 T cells were able to kill GD2+ MB cells. Pretreatment with tazemetostat upregulated GD2 expression, sensitizing GD2dimMB cells to CAR.GD2 T cells cytotoxic activity. In orthotopic mouse models of MB, intravenously injected CAR.GD2 T cells significantly controlled tumor growth, prolonging the overall survival of treated mice. Moreover, the dimerizing drug AP1903 was able to cross the murine blood–brain barrier and to eliminate both blood-circulating and tumor-infiltrating CAR.GD2 T cells.

Conclusions:

Our experimental data indicate the potential efficacy of CAR.GD2 T-cell therapy. A phase I/II clinical trial is ongoing in our center (NCT05298995) to evaluate the safety and therapeutic efficacy of CAR.GD2 therapy in high-risk MB patients.