bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating topographic effects in surface wave tomography based on shortest-path ray tracing
Authors: Du Nanqiao , Yang Tingwei , Xu Tao , Liu Qinya
Published: March 2024

We propose a new method to obtain 3-D shear wave velocity structures for regions with undulating topography based on surface wave dispersion data. In our method, we assume that surface waves propagate along a curved free surface, and the dispersion effects of these waves can be modelled as a frequency-dependent ray tracing problem. We use the shortest-path method to address off-great-circle propagation arising from inhomogeneous elastic parameters and topographic variations. We then apply our method to both synthetic and real-data inversions and demonstrate that ignoring topographic effects may significantly distort the inverted images. Finally, we analysed the accuracy of our method and provided a rule-of-thumb principle to quantitatively assess the need to account for topographic effects in surface wave tomography for a region.
Prognosis-based management of unexplained infertility—why not?
Authors: Shingshetty Laxmi , Wang Rui , Feng Qian , Maheshwari Abha , Mol Ben W
Published: March 2024

Up to a half of couples seeking medical assistance for infertility are diagnosed with unexplained infertility, characterized by normal ovulation, tubal patency, and semen analysis results. This condition presents a challenge in determining the optimal treatment approach. Available treatments include IUI and IVF, but guidelines vary on when to offer each. Prognosis-based management is identified as a research priority, and various prediction models have been developed to guide treatment decisions. Prognostic factors include female age, duration of subfertility, and sperm parameters, among others. Prognosis-based strategies can enhance cost-effectiveness, safety, and patient outcomes, offering less invasive options to those with good prognoses and more aggressive interventions to those with poor prognoses. However, there is a gap between research evidence and its clinical application. In this article, we discuss the application of prognosis-based management in the context of unexplained infertility, highlighting its potential to improve clinical decision-making and patient outcomes.
Non-practicing entities in Europe: an empirical analysis of patent acquisitions at the European Patent Office
Authors: Sterzi Valerio , Maronero Cecilia , Orsatti Gianluca , Vezzulli Andrea
Published: March 2024

This paper delves into the proliferation of non-practicing entities (NPEs), a hot topic in academia and public policy, especially in the United States. The common belief is that Europe is less exposed to NPEs due to a robust patent system, higher enforcement costs, and smaller damage awards. Yet, using a new database of NPE patent applications at the European Patent Office (EPO), the study uncovers that NPEs activity in Europe is arising: they own nearly 20,000 EPO patents, primarily in Electrical Engineering. Moreover, we contribute the literature investigating the heterogeneity of the NPE business model and its relationship with the characteristics and use of the patents they target. Our econometric analysis provides threefold original evidence. First, NPEs with higher propensity for litigation (i.e., “Litigation” NPEs) acquire patents with higher infringement risk but similar technological quality than practicing entities. Second, patent aggregators (i.e., “Portfolio” NPEs) and technology companies (i.e., “Technology” NPEs) acquire higher-quality patents compared to those acquired by practicing entities. Third, patent acquisitions by “Litigation” NPEs and “Portfolio” NPEs reduce the subsequent use of protected technologies.
Randomized comparison of HARVesting the Left Internal Thoracic Artery in a skeletonized versus pedicled technique: the HARVITA trial—study protocol
Authors: Abfalterer Hannes , Ruttmann-Ulmer Elfriede , Grimm Michael , Feuchtner Gudrun , Maier Sarah , Ulmer Hanno , Sandner Sigrid , Zimpfer Daniel , Doenst Torsten , Czerny Martin , Thielmann Matthias , Böning Andreas , Gaudino Mario , Siepe Matthias , Bonaros Nikolaos
Published: March 2024

Latest research has indicated a potential adverse effect on graft patency rates and clinical outcomes with skeletonizing the left internal thoracic artery. We aim to provide a prospective, randomized, multicentre trial to compare skeletonized versus pedicled harvesting technique of left internal thoracic artery concerning graft patency rates and patient survival. A total of 1350 patients will be randomized to either skeletonized or pedicled harvesting technique and undergo surgical revascularization. Follow-up will be performed at 30 days, 1 year, 2 years and 5 years after surgery. The primary outcome will be death or left internal thoracic artery graft occlusion in coronary computed tomography angiography or invasive angiography within 2 years (+/- 3 months) after surgery. The secondary outcome will be major adverse cardiac events (composite outcome of all-cause death, myocardial infarction and repeated revascularization) within 1 year, 2 years and 5 years after surgery. The primary end point will be compared in the modified intention-to-treat population between the two treatment groups using Kaplan–Meier graphs, together with log-rank testing. Hereby, we present the study protocol of the first adequately powered prospective, randomized, multicentre trial which compares skeletonized and pedicled harvesting technique of left internal thoracic artery regarding graft patency rates and patient survival.
Establishment of humanised xenograft models as in vivo study for lung metastasis of osteosarcoma
Authors: Khamarudin Farhana , Muhamad Mudiana , Johari Ibahim Mohamad , Wan Mohamad Zain Wan Nor I’zzah , Aziz Mardiana Abdul , Adib Ridzuan Nurul Raudzah , Ab-Rahim Sharaniza
Published: March 2024

Humanised xenograft models and cancer cell lines are widely used for preclinical drug evaluation, biological studies, and targeted therapy strategies in cancer research. A humanised mouse model is a laboratory mouse that has been genetically modified to contain specific human genes, cells, or tissues. By introducing human-specific elements into rodents, researchers can create a more accurate representation of human physiological and pathological processes. Lacking an appropriate animal model for osteosarcoma (OS), hindered understanding of underlying mechanisms in OS metastasis progression. Markedly, metastasis influences the prognosis and treatment of osteosarcoma. Gaining insight into the mechanisms and occurrences of metastasis could potentially facilitate oncologists in improving therapies. Hence, it is important to develop a lung metastatic OS model to study the basic biology of its progression. This study has established a tumour-bearing mouse model using HOS-143B cell line which was injected into male NOD.SCID gamma (NSG) mice at two locations; intramuscularly (hind leg) and subcutaneously (back) respectively. The primary and metastatic tumour size was monitored by palpating the area of tumour induced and quantified using digital calliper. H&E staining was performed by pathologist to confirm metastasis. Our results showed that mice injected with 1 million cancer cells were unable to produce tumours. Meanwhile, mice injected with three million cancer cells showed tumour development and lung metastasis after 25 days of cancer cell inoculation. In conclusion, this study has successfully established a lung metastatic OS mouse model that could be useful for biological studies of OS. These findings imply that this model is essential for safety and efficacy before clinical trials, accelerate the translation from basic research to therapeutic applications.
Performance of Fentanyl Immunoassays in an ED Patient Population
Authors: Mills Catherine M , Dryja Parker C , Champion-Lyons Elizabeth , Keppler Charles , Babic Nikolina
Published: March 2024

Background

Fentanyl is a synthetic opioid fueling the current opioid crisis in the United States. While emergency department (ED) visits due to opioid-related overdoses, injection complications, and withdrawals become increasingly more frequent, fentanyl is not detected in routine toxicology testing. We evaluated 2 FDA-approved fentanyl immunoassays in a sampled ED population.

Methods

De-identified, remnant urine specimens (n = 213) collected from patients presenting to a large ED were analyzed using ARK Fentanyl II (ARK II) and Immunalysis SEFRIA (SEFRIA) fentanyl immunoassays on an Architect c16000 (Abbott) analyzer. All discrepant specimens were evaluated by LC-MS/MS. Additionally, polysubstance abuse patterns and trends were analyzed.

Results

While intra-assay imprecision was comparable for ARK II and SEFRIA, inter-assay imprecision for ARK II and SEFRIA varied from 8.0% to 1.8% and from 37% to 12.5%, respectively. SEFRIA had a marginally higher false-positivity rate (3%) than ARK II (1%). Both assays had equivalent sensitivity of 95%, with ARK II (99%) having greater specificity than SEFRIA (97%). Fentanyl was detected in 13.7% of drug-panel-positive patient samples and most frequently observed in patients also testing positive for amphetamines and cocaine. Notably, fentanyl was detected in 5.3% of patient samples that were negative for all other drugs in our standard toxicology panel.

Conclusions

A sizable portion of drug-positive samples from our ED were positive for fentanyl, with a subset of patients testing positive for fentanyl alone. Implementation of fentanyl testing into routine toxicology panels can elucidate polysubstance abuse paradigms and capture ED patients that would go undetected in standard panels.
Comparative phenotypic and genotypic analysis of community-acquired and hospital-acquired intra-abdominal infections among liver transplanted patients
Authors: Elmanakhly Arwa R , Safwat Nesreen , Tohamy Sally T K , Elsayed Khaled M , ElSherif Heba M , Elsayed Mahitab , El-Tarabili Reham M , Alhomrani Majid , Alamri Abdulhakeem S , Ghoneim Mohammed M , Alshahrani Mohammed A , Saif Ahmed , Mansour Abdallah T , Bendary Mahmoud M
Published: March 2024

Aim

During liver transplantation, both hospital-acquired (HA) and community-acquired (CA) intra-abdominal infections (IAIs) are involved causing life-threatening diseases. Therefore, comparative studies of aerobic and facultative anaerobic HA-IAIs and CA-IAIs after liver transplantation surgery are necessary.

Methods and results

The species of detected isolates (310) from intra-abdominal fluid were identified and classified into hospital-acquired intra-abdominal infections (HA-IAIs) and community-acquired intra-abdominal infections (CA-IAIs). Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were the most commonly detected species. The resistant phenotypes were commonly detected among the HA-IAIs; however, the virulent phenotypes were the predominant strains of CA-IAIs. Regrettably, the resistance profiles were shocking, indicating the inefficacy of monotherapy in treating these isolates. Therefore, we confirmed the use of empirical combination therapies of amikacin and meropenem for treating all IAIs (FICI ≤ 0.5). Unfortunately, the high diversity and low clonality of all identified HA and CA-IAIs were announced with D-value in the range of 0.992–1.

Conclusion

This diversity proves that there are infinite numbers of infection sources inside and outside healthcare centers.
Competent or Sad Blue? Lively or Aggressive Red? Why, How, and When Background Color Shapes the Meanings of Logo Hues
Authors: Celhay Franck , Luffarelli Jonathan
Published: March 2024

Why, how, and when can logos with a blue positive space communicate competence versus sadness? Why, how, and when might logos with a red positive space evoke impressions of liveliness versus aggressiveness? As the current research establishes, a black background strengthens the negative meanings associated with the hue of a logo’s positive space and weakens its positive meanings. Conversely, a white background strengthens its positive meanings and weakens its negative meanings. These automatic effects occur because the hue of the positive space interacts with the color of the negative space to determine whether logos communicate positive or negative brand impressions more vividly. These effects are broadly applicable to both well-known and unknown brands, yet they are attenuated for meaningful logos and filled-frame logos. With these novel findings, this article identifies specific factors that can alter the meanings of logo hues, provides a theoretical lens for understanding the interplay of the background color and the hue of the positive space, and offers guidelines for crafting effective logos. This article also reveals which brands can benefit most from conveying negative impressions through their logos: logos with a black (white) background enhance evaluations of brands that possess negatively (positively) valenced personality traits.
Geophysical characterization of lamproite fields in the Dharwar craton using VLF-EM and advanced filtering techniques: insights from conductivity analysis and analytical signal mapping
Authors: Jonnalagadda Ravi , Mathur Ram Raj , Sridhar A
Published: March 2024

This study presents a geophysical investigation of the lamproite fields located in the Dharwar craton, aiming to map conductivity variations using contemporary techniques. The study employs very low-frequency electromagnetic (VLF-EM) methods, applying Hilbert transformations, and first-order vertical derivatives to the Fraser and Karous–Hjelt filtered contoured of VLF-EM data. The peninsular gneissic complex (PGC) granitic rocks in the study area experienced tectonic forces, resulting in fractures along specific WNW–ESE to NW–SE trends. Within these crustal weak zones, these lamproites are emplaced. The lamproite pipes are volcanic rocks. As a result, the top portions are weathered and tend to conductive, and the conductivity tends to decrease with depth. The volumetric size of lamproites ranges from centimetres to hundreds of metres, unlike kimberlites that are larger. Hence, the exploration of lamproites poses challenges. The contours of in-phase and quadrature components were used to identify the cluster of lamproite zones within the study area. From this study, the boundaries of the lamproite pipes were clearly identified using real component's analytical and first-order vertical derivative signal contour maps. The VLF-EM pseudo-depth current density section was used to identify anomalous lamproite, pipes, and their subsurface extensions, along with the surrounding formations. The current investigation findings specify that the lamproites exhibit weak conductive. These results provide valuable insights for exploration efforts within the Dharwar craton, and can aid in the identification and mapping of the lamproite fields.
Mr. Gilbert’s World Tour: Rethinking Disabled Veterans Across British Imperial Spaces
Authors: Robinson Michael
Published: March 2024

This article provides a comparative analysis of the treatment of disabled First World War veterans in 1920s Britain and the simultaneous care of Imperial Pensioners residing in Australia and South Africa via the detailed administrative reports of a British civil servant, G.F. Gilbert. Imperial Pensioners were disabled veteran migrants of the British Army residing overseas. A study of these veteran populations in Australia and South Africa provides two primary insights into the broader historiography of disabled veterans. Firstly, a comparative case study helps to show the way in which cultural notions of disability were part of broader ideas of nation-building overseas. Secondly, the specific disability diagnosis category chosen as a more in-depth case study can further complicate and contradict broader assessments of national responses. This article attempts to build upon recent transnational histories of veterans by transcending national boundaries and homogenous veteran profiles with an extension in methodological scope by providing an intra-national case study via the Imperial Pensioner.
Inspiration or infringement? Social media ‘viral’ trends: a case study on TikTok
Authors: Galea Michela
Published: March 2024

Short-form videos have recently gained popularity thanks to social media platforms like TikTok. Some of the videos created by users go ‘viral’ and are ‘reproduced’ by others as they become trends on this platform.

This article examines whether viral social media trends can warrant copyright protection and whether, by recreating such trends without permission, a potential infringement takes place. The idea–expression dichotomy will form the basis of the analysis so that the question is whether the infringer merely borrows an unprotected idea or rather copies a protectable expression.

Additionally, as hinted in the pending referral in Mio (C-580/23), the Court of Justice of the European Union (CJEU) is yet to determine how the assessment of similarity, when examining an alleged infringement, must be conducted—is this one of recognizability or rather overall impression? Exceptions and limitations—most pertinently, pastiche—also form part of the discussion as questions are raised on the application of this undefined concept, pending the judgment in Pelham II (C-590/23).

A balancing approach shall be taken between the interests of the different stakeholders at hand, including having regard to freedom of expression and protection of IP.
Platycodin D facilitates antiviral immunity through inhibiting cytokine storm via targeting K63-linked TRAF6 ubiquitination
Authors: Liu Hui , Xu Lirong , Lu Enhao , Tang Chenchen , Zhang Hanxiao , Xu Yanwu , Yu Yuanyuan , Ong Naomi , Yang Xiao-Dong , Chen Qilong , Zheng Yuejuan
Published: March 2024

Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases. As one of the major terpenoid saponins extracted from P. grandiflorum, Platycodin D (PD) has been reported to play several roles, including anti-inflammation, analgesia, anticancer, hepatoprotection, and immunoregulation. However, the therapeutic roles of PD to treat influenza virus infection remain unknown. Here, we show that PD can protect the body weight loss in severely infected influenza mice, alleviate lung damage, and thus improve the survival rate. More specifically, PD protects flu mice via decreasing the immune cell infiltration into lungs and downregulating the overactivated inflammatory response. Western blot and immunofluorescence assays exhibited that PD could inhibit the activation of TAK1/IKK/NF-κB and MAPK pathways. Besides that, cellular thermal shift assay, surface plasmon resonance, and immunoprecipitation assays indicated that PD binds with TRAF6 to decrease its K63 ubiquitination after R837 stimulation. Additionally, small interfering RNA interference experiments exhibited that PD could inhibit the secretion of interleukin-1β and tumor necrosis factor α in TRAF6-dependent manner. Altogether, our results suggested that PD is a promising drug candidate for treating influenza. Our study also offered a scientific explanation for the commonly used P. grandiflorum in many antiepidemic classic formulas. Due to its host-directed regulatory role, PD may serve as an adjuvant therapeutic drug in conjunction with other antiviral drugs to treat the flu.
Have courage and be kind: gender depictions, female empowerment, and modern audience ratings in film adaptations of Cinderella from 1914 to 2022
Authors: Shawcroft Jane , Jorgensen-Wells McKell A , Coyne Sarah M , Rogers Adam A , Meldrum Madeleine
Published: March 2024

Fairytales may represent a unique genre of media well-suited to depict feminine traits as valuable to characters of all genders by positioning traditionally feminine-coded traits as sources of strength and power to characters in fairytale plots. To examine this theoretical supposition, this study examines the association between indices of female empowerment (United States), modern audience ratings of films, and gendered depictions within 31 film adaptations of Cinderella produced over the span of 100 years. Results indicate Cinderella was consistently depicted as more feminine and the Prince more masculine, but both Cinderella and the Prince consistently displayed both masculine and feminine traits—providing mixed evidence of the renegotiation of gender in fairytales. Cinderella’s femininity was negatively related to indices of female empowerment, but positively related to modern audience ratings, suggesting possible tension between the production and consumption of gendered media in this context.
Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism
Authors: Zhang Junjie , Qi Ao , Shen Jing , Liu Lulu , Cai Chun , Xu Hui
Published: March 2024

Objectives

Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear.

Methods

Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC–MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated.

Results

We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment.

Conclusion

Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism
A rare complication in percutaneous nephrolithotomy: clinical case and implications
Authors: Nedjim Saleh Abdelkerim , Berdé Hissein Hagguir , Kbirou Adil , Moataz Amine , Dakir Mohamed , Debbagh Adil , Aboutaieb Rachid
Published: March 2024

Percutaneous nephrolithotomy has become the standard procedure for the management of large kidney stones. Compared with other endo-urological techniques, it has a better fragmentation rate in a single session for kidney stones over 20 mm. It is therefore the recommended first-line treatment modality for large kidney stones. Bleeding is a well-known complication of this procedure, often requiring transfusion. In 0.8% of cases, bleeding can be severe, requiring surgical intervention to control hemostasis. Damage to the lumbar artery is a very rare event, and a potential complication. To our knowledge, this is the first report of lumbar artery involvement during percutaneous nephrolithotomy, complicated by severe bleeding and hemodynamic instability, necessitating conversion. Surgical exploration revealed a severed and bleeding lumbar artery. After hemostasis control by coagulation and ligation, the patient became stable. The patient was discharged on D3, where ureteroscopic lithotripsy was planned after collegial discussion with the patient. Based on this experience, it is important for the surgeon to have in mind certain principles and a thorough knowledge of the classic lateral lumbotomy approach to the kidney.
Are high-throughput root phenotyping platforms suitable for informing root system architecture models with genotype-specific parameters? An evaluation based on the root model ArchiSimple and a small panel of wheat cultivars
Authors: Nguyen Hong Anh , Martre Pierre , Collet Clothilde , Draye Xavier , Salon Christophe , Jeudy Christian , Rincent Renaud , Muller Bertrand
Published: March 2024

Given the difficulties in accessing plant roots in situ, high-throughput root phenotyping (HTRP) platforms under controlled conditions have been developed to meet the growing demand for characterizing root system architecture (RSA) for genetic analyses. However, a proper evaluation of their capacity to provide the same estimates for strictly identical root traits across platforms has never been achieved. In this study, we performed such an evaluation based on six major parameters of the RSA model ArchiSimple, using a diversity panel of 14 bread wheat cultivars in two HTRP platforms that had different growth media and non-destructive imaging systems together with a conventional set-up that had a solid growth medium and destructive sampling. Significant effects of the experimental set-up were found for all the parameters and no significant correlations across the diversity panel among the three set-ups could be detected. Differences in temperature, irradiance, and/or the medium in which the plants were growing might partly explain both the differences in the parameter values across the experiments as well as the genotype × set-up interactions. Furthermore, the values and the rankings across genotypes of only a subset of parameters were conserved between contrasting growth stages. As the parameters chosen for our analysis are root traits that have strong impacts on RSA and are close to parameters used in a majority of RSA models, our results highlight the need to carefully consider both developmental and environmental drivers in root phenomics studies.
In vitro investigation of the effects of Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 exopolysaccharides on tight junction damage caused by influenza virus infection
Authors: Ishikawa Hiroki , Kuno Yoshihiro , Yokoo Takehiro , Nagashima Ryuichi , Takaki Takashi , Sasaki Hiraku , Kohda Chikara , Iyoda Masayuki
Published: March 2024

It is a problem that influenza virus infection increases susceptibility to secondary bacterial infection in lungs leading to lethal pneumonia. We previously reported that exopolysaccharides (EPS) derived from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1) could prevent against influenza virus infection followed by secondary bacterial infection in vitro. Therefore, the present study assessed whether EPS derived OLL1073R-1 protects the alveolar epithelial barrier disfunction caused by influenza virus infection. After A549 cells treated with EPS or without EPS were infected influenza virus A/Puerto Rico/8/34 (IFV) for 12 h, the levels of tight junction genes expression and inflammatory genes expression were measured by reverse transcription polymerase chain reaction. As results, EPS treatment could protect against low-titer IFV infection, but not high-titer IFV infection, followed by suppression of the increased expression of inflammatory cytokine gene levels and recovery of the decrease in the expression level of ZO-1 gene that was caused by low-titer IFV infection, leading to an improvement trend in the barrier function. Our findings showed that EPS derived from OLL1073R-1 could inhibit low-titer IFV infection leading to maintenance of the epithelial barrier function through the suppression of inflammatory cytokine genes expression.
COVID-19 associated candidemia: From a shift in fungal epidemiology to a rise in azole drug resistance
Authors: Najafzadeh Mohammad Javad , Shaban Tahmineh , Zarrinfar Hossein , Sedaghat Alireza , Hosseinikargar Neginsadat , Berenji Fariba , Jalali Mahsa , Lackner Michaela , James Jasper Elvin , Ilkit Macit , Lass-Flörl Cornelia
Published: March 2024

Our understanding of fungal epidemiology and the burden of antifungal drug resistance in COVID-19-associated candidemia (CAC) patients is limited. Therefore, we conducted a retrospective multicenter study in Iran to explore clinical and microbiological profiles of CAC patients. Yeast isolated from blood, were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method M27-A3 protocol. A total of 0.6% of the COVID-19 patients acquired CAC (43/6174). Fluconazole was the most widely used antifungal, and 37% of patients were not treated. Contrary to historic candidemia patients, Candida albicans and C. tropicalis were the most common species. In vitro resistance was high and only noted for azoles; 50%, 20%, and 13.6% of patients were infected with azole-non-susceptible (ANS) C. tropicalis, C. parapsilosis, and C. albicans isolates, respectively. ERG11 mutations conferring azole resistance were detected for C. parapsilosis isolates (Y132F), recovered from an azole-naïve patient. Our study revealed an unprecedented rise in ANS Candida isolates, including the first C. parapsilosis isolate carrying Y132F, among CAC patients in Iran, which potentially threatens the efficacy of fluconazole, the most widely used drug in our centers. Considering the high mortality rate and 37% of untreated CAC cases, our study underscores the importance of infection control strategies and antifungal stewardship to minimize the emergence of ANS Candida isolates during COVID-19.
Resolved properties of classical bulge and pseudo-bulge galaxies
Authors: Hu Jia , Wang Lan , Ge Junqiang , Zhu Kai , Zeng Guangquan
Published: March 2024

We compare properties of classical and pseudo-bulges and properties of their hosting galaxies selected from the MaNGA survey. Bulge types are identified based on the Sérsic index n of bulge component and the position of bulges on the Kormendy diagram. For the 393 classical bulges and 422 pseudo-bulges selected and their hosting galaxies, we study their kinematic properties including a proxy for specific angular momentum and central velocity dispersion, their stellar population properties including stellar age, metallicity, and specific star formation rate, as well as H i fractions of the galaxies. Our results show that at given stellar mass, disc components of pseudo-bulge galaxies are younger, have more active star formation, rotate more, and may contain more H i content compared with those of classical bulge galaxies, and the differences are larger than those between bulges themselves. The correlations between bulge types and disc properties indicate that different types of bulges are shaped by different processes that may regulate both growth of central components and evolution of outer discs in galaxies. In addition, we propose a stellar mass dependent divider of central velocity dispersion to separate galaxies with classical bulges from those with pseudo-bulges in galaxy mass range of $10.4\lt \mathrm{log}(M_*/\rm M_\odot)\lt 11.4$: $\mathrm{log}(\sigma _0) = 0.23 \times \mathrm{log}(M_*/\rm M_\odot)-0.46$. Galaxies with larger/smaller σ0 can be classified as hosts of classical/pseudo-bulges.
Timing analysis of the newly discovered black hole candidate Swift J1727.8−1613 with Insight-HXMT
Authors: Yu Wei , Bu Qing-Cui , Zhang Shuang-Nan , Liu He-Xin , Zhang Liang , Ducci Lorenzo , Tao Lian , Santangelo Andrea , Doroshenko Victor , Huang Yue , Yang Zi-Xu , Qu Jin-Lu
Published: March 2024

We present the results obtained from an X-ray timing study of the new black hole candidate Swift J1727.8−1613. The work is based on Hard X-ray Modulation Telescope (Insight-HXMT) observations carried out during the 2023 outburst. Prominent type-C low-frequency Quasi-periodic Oscillations (LFQPOs) are detected throughout the observations. With the substantial effective area of the Insight-HXMT at high energies, we examine the energy dependence of various parameters, including the centroid frequency, fractional rms, and phase lags of the type-C QPOs. Our findings align closely with those observed in high-inclination systems. During the initial stage of the outburst, a peaked noise component is also detected, the frequency of which is highly correlated with the LFQPO frequency, aligning with the Psaltis–Belloni–van der Klis relation. By assuming that the peaked noise originates from the precession of the accretion disc, the spin of this source can be constrained. Our results suggest that this source may possess a high spin.
Radio-to-submillimetre spectral energy distributions of NGC 1365
Authors: Chen Guangwen , Bendo George J , Fuller Gary A , Zhang Hong-Xin , Kong Xu
Published: March 2024

We analyse the radio-to-submillimetre spectral energy distribution (SED) for the central pseudo-bulge of NGC 1365 using archival data from the Atacama Large Millimeter/submillimeter Array (ALMA) and the Very Large Array. This analysis shows that free–free emission dominates the continuum emission at 50–120 GHz and produces about 75 per cent of the 103 GHz continuum emission. However, the fraction of 103 GHz continuum emission originating from free–free emission varies significantly among different subregions in the pseudo-bulge, particularly for an outflow from the active galactic nuclei (AGN) on the eastern pseudo-bulge where the synchrotron emission produces half of the 103 GHz continuum emission. Free–free emission also dominates at 103 GHz within the central 400 pc diameter region, but this emission is associated with the AGN rather than star formation. The star formation rate (SFR) within the pseudo-bulge derived from the ALMA free–free emission is 8.9 ± 1.1 M⊙ yr−1. This is comparable to the SFR from the mid-infrared emission but higher than the SFR from the extinction-corrected H α line emission, mainly because the pseudo-bulge is heavily dust obscured. The 1.5 GHz emission yields a comparable SFR for the pseudo-bulge but may have lower SFRs within subregions of the pseudo-bulge because of the diffusion outside of these regions of the electrons producing the synchrotron radiation. We propose that applying a correction factor of 75 per cent to the 80–110 GHz continuum emission could provide valuable estimates of the free–free emission without performing any SED decomposition, which could derive extinction-free SFRs within 20 per cent accuracy.
The Origin and Evolution of Sex Peptide and Sex Peptide Receptor Interactions
Authors: Peng Junhui , Svetec Nicolas , Molina Henrik , Zhao Li
Published: March 2024

Post-mating responses play a vital role in successful reproduction across diverse species. In fruit flies, sex peptide binds to the sex peptide receptor, triggering a series of post-mating responses. However, the origin of sex peptide receptor predates the emergence of sex peptide. The evolutionary origins of the interactions between sex peptide and sex peptide receptor and the mechanisms by which they interact remain enigmatic. In this study, we used ancestral sequence reconstruction, AlphaFold2 predictions, and molecular dynamics simulations to study sex peptide–sex peptide receptor interactions and their origination. Using AlphaFold2 and long-time molecular dynamics simulations, we predicted the structure and dynamics of sex peptide–sex peptide receptor interactions. We show that sex peptide potentially binds to the ancestral states of Diptera sex peptide receptor. Notably, we found that only a few amino acid changes in sex peptide receptor are sufficient for the formation of sex peptide–sex peptide receptor interactions. Ancestral sequence reconstruction and molecular dynamics simulations further reveal that sex peptide receptor interacts with sex peptide through residues that are mostly involved in the interaction interface of an ancestral ligand, myoinhibitory peptides. We propose a potential mechanism whereby sex peptide–sex peptide receptor interactions arise from the preexisting myoinhibitory peptides–sex peptide receptor interface as well as early chance events both inside and outside the preexisting interface that created novel sex peptide-specific sex peptide–sex peptide receptor interactions. Our findings provide new insights into the origin and evolution of sex peptide–sex peptide receptor interactions and their relationship with myoinhibitory peptides–sex peptide receptor interactions.
Simulation-based caregiving skills training for family members of high-grade glioma patients
Authors: Whisenant Meagan , Weathers Shiao-Pei , Li Yisheng , Aldrich Ellen , Ownby Kristin , Thomas Jessica , Ngo-Huang An , Bruera Eduardo , Milbury Kathrin
Published: March 2024

Background

Because family caregivers of patients with a high-grade glioma experience high levels of distress and feel unprepared to perform the complex caregiving tasks associated with the disease and its treatment, we pilot-tested a caregiving skills intervention that integrates hands-on caregiving with coping skill training.

Methods

In this single-arm trial, caregivers participated in a 4-session research nurse-led intervention involving simulation-based caregiving skills training at the hospital and psychoeducation delivered via videoconference. We collected measures of patients’ and caregivers’ psychological symptoms; caregivers’ caregiving self-efficacy and role adjustment; and patients' cancer-related symptoms (MDASI) at baseline and again postintervention. We tracked feasibility data.

Results

We approached 29 dyads of which 10 dyads (34%) consented. All patients (mean age: 60 years, 89% male) and caregivers (mean age: 58 years, 80% female, 80% spouses) completed the baseline and 7 dyads completed the follow-up assessments (attrition was related to patient’s hospice transfer). Seven caregivers completed all 4 sessions and rated the program as beneficial. Paired t-tests revealed a significant improvement in caregiving self-efficacy at 6 weeks postintervention (t = –3.06, P = .02). Although improvements in caregiver role adjustment and patient and caregiver symptoms were not observed, no decreases in symptom burden or role adjustment were found during the follow-up period.

Conclusions

This novel supportive care program appears to be safe, feasible, acceptable, and perceived as useful for caregivers of patients with high-grade glioma. Based on feasibility indicators and a signal of intervention efficacy, a randomized controlled trial is warranted.
Thylakoid supplementation and hunger and fullness perception: a systematic review and dose-response meta-analysis of randomized controlled trials
Authors: Nikrad Negin , Sarghein Mehdi Ghaffari , Abbasalizad Farhangi Mahdieh
Published: March 2024

Context

It has been suggested that thylakoid supplementation could be associated with favorable changes in appetite. However, the present trials are inconsistent.

Objective

This systematic review and meta-analysis aimed to investigate whether thylakoid supplementation is effective in hunger/fullness changes.

Data Sources

A comprehensive literature search was performed before conducting a systematic search in PubMed, Scopus, and ISI Web of Sciences databases up to May 2023.

Data Extraction

Of the 262 articles found, 5 articles that measured hunger fullness expressed as ratings on the visual analog scale (VAS) for appetite analyses were selected and thoroughly examined. Relevant information, such as the authors' names, year of publication, country of origin, study design, number and status of participants, intervention dosage and type, study duration, assay used, and key findings, was extracted from these articles. The Jadad scale was used to evaluate the quality of studies.

Data Analysis

The data were obtained using STATA version 13 (StataCorp). Effect sizes were reported as weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup analyses were performed to estimate whether the effects of thylakoid supplementation on hunger and fullness varied according to dose, intervention duration, baseline population age and body mass index, baseline hunger and fullness, total sample size, and study quality. Fractional polynomial modeling was carried out to estimate time- and dose-response meta-analysis of the association between thylakoid and satiety and fullness. The meta-analysis also suggests a significant association between the combination of thylakoids with meals and reduced hunger (WMD: –2.415 mm; 95% CI: –3.544, –1.287; P < 0.001) and increased fullness (WMD: +4.602 mm; 95% CI: 2.356, 6.848; P < 0.001). Further analysis showed that thylakoid supplementation with 2 doses of 5 g/day (P = 0.002) and 7.4 g/day (P = 0.021) is more effective in reducing the feeling of hunger during an intervention of less than 56 days (P < 0.001) and with a lower level of hunger (VAS <45 mm, P < 0.001). Furthermore, a significant increase in the perception of fullness was found at a duration of less than 84 days (P < 0.001) and baseline fullness of more than 45 mm (P < 0.001).

Conclusions

Supplementation with thylakoid shows favorable effects on reducing hunger and increasing fullness during a shorter intervention duration. Further trials are required to shed light on this relationship.

Systematic Review Registration

PROSPERO registration no. CRD42023432429.
Drug Exposure of Long-Acting Cabotegravir and Rilpivirine in Older People With Human Immunodeficiency Virus: A Pharmacokinetic Modeling Study
Authors: Bettonte Sara , Berton Mattia , Stader Felix , Battegay Manuel , Marzolini Catia
Published: March 2024

Background

The life expectancy of people with human immunodeficiency virus (PWH) has significantly increased, thanks to combined antiretrovirals with improved potency and tolerability. One further step has been achieved with the development of long-acting (LA) injectable antiretrovirals, which allow for infrequent dosing. However, the pharmacokinetics of LA antiretrovirals has been poorly characterized in older PWH, as they are generally excluded from trials. We performed virtual studies using physiologically based pharmacokinetic (PBPK) modeling to determine the anticipated exposure of LA cabotegravir/rilpivirine in older individuals.

Methods

Our PBPK model was verified against available observed data for LA cabotegravir and rilpivirine. Cohorts of virtual individuals aged 20–50, 50–65, or 65–85 years were generated to simulate the exposure of LA cabotegravir/rilpivirine for each age group. The fold changes in trough concentration (Cmin) and in drug exposure (area under the time-concentration curve [AUC]) were determined for older relative to young individuals.

Results

The verified PBPK models predicted an increase in exposure within the 0.8–1.25 fold range for monthly LA cabotegravir/rilpivirine. The Cmin and AUC were predicted to be 29% and 26% higher in older compared with young adults for LA cabotegravir administered bimonthly (every 2 months) and 46% and 41% higher for LA rilpivirine bimonthly. The Cmin and AUC of LA cabotegravir and rilpivirine were predicted to be modestly increased in female compared with male individuals for all age groups.

Conclusions

LA cabotegravir/rilpivirine exposure and trough concentrations are predicted to be higher in older than in young PWH; thus, older adults could have a lower risk to present suboptimal concentrations during the dosing interval.
Identifying General Practitioners’ Antibiotic Prescribing Profiles Based on National Health Reimbursement Data
Authors: Arias Pauline , Matta Matta , Strazzulla Alessio , Le Mener Christine , Gallien Sébastien , Diamantis Sylvain
Published: March 2024

Background

Antibiotic selection pressure in human medicine is a significant driver of antibiotic resistance in humans. The primary aspect of antibiotic consumption is associated with general practitioner (GP) prescriptions. We aimed to identify prescriber profiles for targeted antimicrobial stewardship programs using novel indicators.

Methods

A cross-sectional study was conducted in 2018 investigating GPs’ antibiotic prescriptions in a French department, utilizing the reimbursement database of the national health service. Three antibiotic prescribing indicators were used. Specific targets were established for each indicator to identify the antibiotic prescribers most likely contributing to the emergence of resistance.

Results

Over 2018, we had 2,908,977 visits to 784 GPs, leading to 431,549 antibiotic prescriptions. Variations between GPs were shown by the 3 indicators. The median antibiotic prescription rate per visit was 13.6% (interquartile range [IQR], 9.8%–17.7%). Median ratios of the prescriptions of low-impact antibiotics to the prescriptions of high-impact antibiotics and of amoxicillin prescriptions to amoxicillin–clavulanic acid prescriptions were 2.5 (IQR, 1.7–3.7) and 2.94 (IQR, 1.7–5), respectively. We found 163 (21%) high prescribers of antibiotics with 3 distinct patterns: The first group overuses broad-spectrum antibiotics but without an overprescription rate per visit, the second group displays an overprescription rate but no excessive use of broad-spectrum antibiotics, and the third group shows both an overprescription rate and excessive use of broad-spectrum antibiotics.

Conclusions

Prescription-based indicators enable the identification of distinct profiles of antibiotic prescribers. This identification may allow for targeted implementation of stewardship programs focused on the specific prescribing patterns of each profile.
Regulatory networks in plant responses to drought and cold stress
Authors: Kim June-Sik , Kidokoro Satoshi , Yamaguchi-Shinozaki Kazuko , Shinozaki Kazuo
Published: March 2024

Drought and cold represent distinct types of abiotic stress, each initiating unique primary signaling pathways in response to dehydration and temperature changes, respectively. However, a convergence at the gene regulatory level is observed where a common set of stress-responsive genes is activated to mitigate the impacts of both stresses. In this review, we explore these intricate regulatory networks, illustrating how plants coordinate distinct stress signals into a collective transcriptional strategy. We delve into the molecular mechanisms of stress perception, stress signaling, and the activation of gene regulatory pathways, with a focus on insights gained from model species. By elucidating both the shared and distinct aspects of plant responses to drought and cold, we provide insight into the adaptive strategies of plants, paving the way for the engineering of stress-resilient crop varieties that can withstand a changing climate.
Physical coupling of H3K4me3 demethylases and Polycomb repressive complex 2 to accelerate flowering in rice
Authors: Xuan Hua , Shi Nan , Chen Jianhao , Jiang Yili , Zhang Hao , Chu Chuanliang , Li Shaoqing , Chen Xiangsong , Yang Hongchun
Published: March 2024

Two H3K4me3 demethylases physically interact with the Polycomb repressive complex 2, thereby altering methylation of a key flowering locus and promoting rice flowering.