bluuebunny/crossref_metadata_2025 huggingface dataset:
Soldier phenotypic differences among 2 invasive and destructiveCoptotermesspecies and their hybrids (Blattodea: Isoptera: Rhinotermitidae)
Authors: Patel Jayshree S , Chouvenc Thomas , Wu Chia-Chien , Li Hou-Feng , Su Nan-Yao
Published: November 2023

With recent evidence of hybridization events in the field, the phenotypic traits of F1 hybrid colonies of 2 destructive subterranean termite species, Coptotermes formosanus Shiraki and Coptotermes gestroi (Wasmann) remain to be investigated. In this study, laboratory colonies of 2 conspecific pairings and 2 heterospecific pairings (hybrid F = ♀C. formosanus × ♂C. gestroi, hybrid G = ♀C. gestroi × ♂C. formosanus) were examined in Florida, USA, and in Taiwan. Colony nest architecture for both hybrids displayed disorganized carton materials compared to the defined trabecular carton of both parental species. Soldier head measurements were not a reliable approach for diagnostic purposes, as soldier morphometric traits widely overlapped across all mating combinations, except for hybrid F soldiers displaying abnormally long mandibles. Hybrid F soldiers’ mandibles also remained parallel when at rest. However, 4 qualitative morphological differences in soldiers were determined for diagnostic purposes. First, the fontanelle in both hybrids is horizontally ellipsoid whereas subcircular in C. gestroi and trianguliform in C. formosanus. Second, sclerotized striations along the postmental sulcus are present in C. gestroi, absent in C. formosanus, and intermediate in both hybrid soldier types. Third, each lateral margin of the fontanelle is flanked by 2 setae in C. formosanus and both hybrids, while a single seta resides on each side of the fontanelle in C. gestroi. Finally, C. gestroi and hybrid soldiers’ heads are characterized by a bulging vertex that is lacking in C. formosanus. Therefore, a combination of these 4 characteristics now allows for soldier identification of hybrid Coptotermes.
Rare but clinically important salivary gland-type tumor of the lung: A review
Authors: Takamori Shinkichi , Yatabe Yasushi , Osoegawa Atsushi , Aokage Keiju , Yoshioka Hiroshige , Miyoshi Tomohiro , Mimae Takahiro , Endo Makoto , Hattori Aritoshi , Yotsukura Masaya , Isaka Tetsuya , Isaka Mitsuhiro , Maniwa Tomohiro , Nakajima Ryu , Watanabe Shun-ichi
Published: November 2023

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.
Fitness of the first backcross generations from the second to the sixth progenies of glyphosate-resistant transgenic Brassica napus and wild Brassica juncea in absence of the herbicide
Authors: Huang Lei , Shao Zi-Cheng , Dai Ling-Ling , Zheng Ai-Qin , Zhang Qing-Ling , Wang Xiao-Lei , Qiang Sheng , Song Xiao-Ling
Published: November 2023

Successful introgression of a transgene from a transgenic crop into a wild or weedy relative is determined by the fitness of backcross generations carrying the transgene. To provide insight for ecological risk assessment of gene flow between transgenic Brassica napus and wild Brassica juncea, this study investigated the fitness of the first backcross generations from the second to the sixth progenies (BC1F2R–BC1F6R) between glyphosate-resistant transgenic B. napus and wild B. juncea at low density (5 plants/m2) and high density (10 plants/m2), and monoculture and mixed planting (wild B. juncea: BC1F2R–BC1F6R = 1:1). Correlations between the fitness components of backcross progeny, planting density and planting patterns were analyzed. In the monoculture at low density, compared with B. juncea, earlier generations BC1F2R and BC1F3R had low composite fitness, while later generations from BC1F4R to BC1F6R were more fit. At high density, whatever monoculture or mixed planting, all backcrossed generations had lower composite fitness than B. juncea. Correlation analysis indicated that both planting density and pattern significantly affected the fitness components of the first backcross generations from the second to the sixth progenies (BC1F2R–BC1F6R). These results indicate that the probability of transgene introgression from cultivated B. napus to weedy B. juncea is likely to be highly contingent on the specific growing conditions of their backcross descendants.
Association of HIV Exposure and HIV Infection With In-hospital Mortality Among Hospitalized Infants <1 Year of Age, South Africa, 2016–2018
Authors: Wolter Nicole , Walaza Sibongile , von Mollendorf Claire , von Gottberg Anne , Tempia Stefano , McMorrow Meredith L , Moyes Jocelyn , Treurnicht Florette , Hellferscee Orienka , Moleleki Malefu , Makhasi Mvuyo , Baute Neydis , Cohen Cheryl
Published: November 2023

We enrolled 1323 hospitalized infants aged <1 year in 2016–2018, and examined the association between HIV status and in-hospital mortality. After controlling for confounders, HIV-exposed uninfected infants did not have an increased risk of mortality, whereas infants living with HIV had 4 times greater risk compared with HIV-uninfected infants.
Daily fraction dose-adjusted radiotherapy policy to avoid prolonging the overall treatment time for early glottic squamous cell carcinoma: a single-institutional retrospective study
Authors: Dekura Yasuhiro , Yasuda Koichi , Minatogawa Hideki , Uchinami Yusuke , Tsushima Nayuta , Suzuki Takayoshi , Kano Satoshi , Mori Takashi , Nishioka Kentaro , Kobashi Keiji , Katoh Norio , Homma Akihiro , Aoyama Hidefumi
Published: November 2023

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66 Gy in 33 fractions for T1 disease and 70 Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0 to 2.5 Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9 months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes.
Lipofibromatous hamartoma of median nerve: a case report
Authors: Yousef Al-Abbad Fatimah , Al-Khunaizi Sakinah
Published: November 2023

Herein, we report a 48-year-old male with lipofibromatous hamartoma-induced secondary carpal tunnel syndrome, treated successfully with decompression. The patient presented to the emergency with complaints of paresthesia and oedema of the wrists. When non-invasive methods failed to ease symptoms and nerve damage became a big concern, surgical intervention was recommended. Surgery to remove the nerve sheath and expose the carpal tunnel alleviated pressure on the median nerve. After a 3-year follow-up, the patient reported no discomfort, paresthesia, or limitation in wrist or finger movements, indicating a remarkable recovery. The tumour did not recur, and the sensorium was unharmed.
Development of PMA-qPCR assay to accurately and reproducible quantify viable bacteria of Paenibacillus polymyxa
Authors: Guo Jiacai , Fan Fei , Wang Weiliang , Wan Minxi , Li Yuanguang
Published: November 2023

Paenibacillus polymyxa is an important biocontrol bacterium. The combination of propidium monoazide (PMA) and quantitative polymerase chain reactionq (qPCR) has proven effective in quantifying live bacteria from various microorganisms. The objective was to create a PMA-qPCR assay to precisely and consistently measure the number of living bacteria of biocontrol P. polymyxa. The primers were designed for the spo0A gene of P. polymyxa HY96-2. The optimal conditions for treating the target strain with PMA were a PMA concentration of 15 μg/mL, an incubation time of 5 min, and an exposure time of 10 min. The PMA-qPCR method had a limit of quantification (LOQ) of 1.0 × 103 CFU/mL for measuring the amount of viable P. polymyxa bacteria. The PMA-qPCR method is more sensitive than the qPCR method in detecting viable bacteria in the mixtures of viable and dead bacteria. The accuracy and reproducibility of quantifying viable P. polymyxa bacteria using the PMA-qPCR method were higher compared to the plate count method.
Flow morphology of a supersonic gravitating sphere
Authors: Prust Logan J , Bildsten Lars
Published: November 2023

Stars and planets move supersonically in a gaseous medium during planetary engulfment, stellar interactions, and within protoplanetary discs. For a nearly uniform medium, the relevant parameters are the Mach number and the size of the body, R, relative to its accretion radius, RA. Over many decades, numerical and analytical work has characterized the flow, the drag on the body, and the possible suite of instabilities. Only a limited amount of work has treated the stellar boundary as it is in many of these astrophysical settings, a hard sphere at R. Thus, we present new 3D athena++  hydrodynamic calculations for a large range of parameters. For RA ≪ R, the results are as expected for pure hydrodynamics with minimal impact from gravity, which we verify by comparing to experimental wind tunnel data in air. When RA ≈ R, a hydrostatically supported separation bubble forms behind the gravitating body, exerting significant pressure on the sphere and driving a recompression shock, which intersects with the bow shock. For RA ≫ R, the bubble transitions into an isentropic, spherically symmetric halo, as seen in earlier works. These two distinct regimes of flow morphology may be treated separately in terms of their shock stand-off distance and drag coefficients. Most importantly for astrophysical applications, we propose a new formula for the dynamical friction, which depends on the ratio of the shock stand-off distance to RA. That exploration also reveals the minimum size of the simulation domain needed to accurately capture the deflection of incoming streamlines due to gravity.
Asteroseismic g-mode period spacings in strongly magnetic rotating stars
Authors: Rui Nicholas Z , Ong J M Joel , Mathis Stéphane
Published: November 2023

Strong magnetic fields are expected to significantly modify the pulsation frequencies of waves propagating in the cores of red giants or in the radiative envelopes of intermediate- and high-mass main-sequence stars. We calculate the g-mode frequencies of stars with magnetic dipole fields which are aligned with their rotational axes, treating both the Lorentz and Coriolis forces non-perturbatively. We provide a compact asymptotic formula for the g-mode period spacing and universally find that strong magnetism decreases this period spacing substantially more than is predicted by perturbation theory. These results are validated with explicit numerical mode calculations for realistic stellar models. The approach we present is highly versatile: once the eigenvalues λ of a certain differential operator are pre-computed as a function of the magnetogravity and rotational frequencies (in units of the mode frequency), the non-perturbative impact of the Coriolis and Lorentz forces is understood under a broad domain of validity and is readily incorporated into asteroseismic modelling.
Formation of dense filaments induced by runaway supermassive black holes
Authors: Ogiya Go , Nagai Daisuke
Published: November 2023

A narrow linear object extending ∼60 kpc from the centre of a galaxy at redshift z ∼ 1 has recently been discovered and interpreted as shocked gas filament forming stars. The host galaxy presents an irregular morphology, implying recent merger events. Supposing that each of the progenitor galaxies has a central supermassive black hole (SMBH) and the SMBHs are accumulated at the centre of the merger remnant, a fraction of them can be ejected from the galaxy with a high velocity due to interactions between SMBHs. When such a runaway SMBH (RSMBH) passes through the circumgalactic medium (CGM), converging flows are induced along the RSMBH path, and star formation could eventually be ignited. We show that the CGM temperature prior to the RSMBH perturbation should be below the peak temperature in the cooling function to trigger filament formation. While the gas is temporarily heated due to compression, the cooling efficiency increases, and gas accumulation becomes allowed along the path. When the CGM density is sufficiently high, the gas can cool down and develop a dense filament by z = 1. The mass and velocity of the RSMBH determine the scale of filament formation. Hydrodynamical simulations validate the analytical expectations. Therefore, we conclude that the perturbation by RSMBHs is a viable channel to form the observed linear object. Using the analytical model validated by simulations, we show that the CGM around the linear object to be warm ($T \lesssim 2 \times 10^5$ K) and dense ($n \gtrsim 2 \times 10^{-5} (T/2 \times 10^5 \, K)^{-1} \, {\rm cm^{-3}}$).
The minimum measurable eccentricity from gravitational waves of LISA massive black hole binaries
Authors: Garg Mudit , Tiwari Shubhanshu , Derdzinski Andrea , Baker John G , Marsat Sylvain , Mayer Lucio
Published: November 2023

We explore the eccentricity measurement threshold of Laser Interferometer Space Antenna (LISA) for gravitational waves radiated by massive black hole binaries (MBHBs) with redshifted BH masses Mz in the range 104.5–107.5 M⊙ at redshift z = 1. The eccentricity can be an important tracer of the environment where MBHBs evolve to reach the merger phase. To consider LISA’s motion and apply the time delay interferometry, we employ the lisabeta software and produce year-long eccentric waveforms using the inspiral-only post-Newtonian model taylorf2ecc. We study the minimum measurable eccentricity (emin, defined one year before the merger) analytically by computing matches and Fisher matrices, and numerically via Bayesian inference by varying both intrinsic and extrinsic parameters. We find that emin strongly depends on Mz and weakly on mass ratio and extrinsic parameters. Match-based signal-to-noise ratio criterion suggest that LISA will be able to detect emin ∼ 10−2.5 for lighter systems (Mz ≲ 105.5 M⊙) and ∼10−1.5 for heavier MBHBs with a 90 per cent confidence. Bayesian inference with Fisher initialization and a zero noise realization pushes this limit to emin ∼ 10−2.75 for lower-mass binaries, assuming a <50 per cent relative error. Bayesian inference can recover injected eccentricities of 0.1 and 10−2.75 for a 105 M⊙ system with an ∼10−2 per cent and an ∼10 per cent relative errors, respectively. Stringent Bayesian odds criterion ($\ln {\mathcal {B}}\gt 8$) provides nearly the same inference. Both analytical and numerical methodologies provide almost consistent results for our systems of interest. LISA will launch in a decade, making this study valuable and timely for unlocking the mysteries of the MBHB evolution.
The Syriac Legend of Alexander's Gate
Authors: Tesei Tommaso
Published: November 2023

This book is the first monographic study entirely consecrated to the Syriac text entitled Neṣḥānā d-Aleksandrōs (also known as the Syriac Alexander Legend), a seminal text for later Christian and Muslim apocalyptic traditions. While the scholarly consensus commonly dates the Neṣḥānā to the time of the Byzantine emperor Heraclius (r. 610–641 ce), this study demonstrates that an earlier version of the text was produced during the reign of Justinian I (r. 527–565). This new historical contextualization of the text enables one to better delineate the development of politicized forms of apocalypticism during Late Antiquity, a process in which the Neṣḥānā played a decisive role. By analyzing the contents and the ideology of the text, the book explores the origins and developments of important literary motifs of medieval literature worldwide, including the characterization of Alexander as a pious prophet-king (in both Christianity and Islam alike), and the story of the gate that he erects to confine the eschatological nations of Gog and Magog. Moreover, the book sheds light on lesser-known aspects of political debates in the sixth-century Near East and offers historians a valuable insight into important aspects of Justinian’s reign, as seen by an author who was not on the emperor’s payroll.
Debates about Dating and Context of the Neṣḥānā d-Aleksandrōs
Authors: Tesei Tommaso
Published: November 2023

This chapter reviews earlier scholarship on the Neṣḥānā d-Aleksandrōs, with special attention to the scholarly debate over the original date of composition of the Syriac work. The author analyzes the arguments advanced by scholars in favor of an early composition of the Neṣḥānā (i.e., prior to the seventh century) and highlights the shortcomings of some of these arguments. The author then describes the views of those scholars who have argued in favor of a seventh-century composition and who have sought to set the origins of the Syriac work during the reign of Heraclius. The chapter concludes with a review of recent expressions of skepticism concerning the seventh-century dating.
The 940 ag Prophecy
Authors: Tesei Tommaso
Published: November 2023

In this chapter the author demonstrates, by means of philological analysis, that the only passage in the text that clearly indicates a seventh-century dating—the 940 ag prophecy referring to events that occurred between 626 and 629 ce—is in fact an interpolation within an earlier composition dating to the end of the reign of Justinian. This interpolation—the author argues—demonstrates that several decades after its composition, the Syriac work was modified in order to connect it to new historical circumstances, namely the widespread belief in the Byzantine world that the ideal emperor described in the Neṣḥānā had returned in the figure of Heraclius.
The Conflict with Tūbarlaq
Authors: Tesei Tommaso
Published: November 2023

This chapter explores the section of text about the war between Alexander and his Persian rival, Tūbarlaq. Against many previous scholars, the author of this study demonstrates that themes and topoi adopted by the Syriac author do not relate to a specific understanding of the notion of holy war in the seventh century. In fact, he shows that the Neṣḥānā conforms to literary trends observable in earlier Christian texts. Then, he demonstrates that the peace agreements between Alexander and the Persian king Tūbarlaq described in the Neṣḥānā reflect the reality of Roman-Persian peace treaties in the sixth century—not the seventh century, as claimed by many scholars. By formulating an idealized version of the peace contracts stipulated by Justinian and Khosrow Anōshirvān, the Syriac author criticizes the Byzantine policy of buying peace with gold. This chapter connects the author’s criticism of Justinian to broader dissatisfactions in the Byzantine world with the emperor’s poor achievements in the conflicts with the Persians. It also demonstrates that the author’s criticism of Justinian has a close parallel in the work of another sixth-century Syriac writer, the anonymous author of the Julian Romance. Then, it analyzes the prophecy uttered by Tūbarlaq at the end of the Neṣḥānā and argues against the view that this prophecy echoes themes of Heraclius’s war propaganda. Finally, it addresses the unsolved problem of Tūbarlaq’s identity and offers a new solution for this question.
The Syriac Alexander
Authors: Tesei Tommaso
Published: November 2023

This chapter situates the figure of Alexander in the Neṣḥānā in relation to the well-known phenomenon of the imitatio Alexandri, adopted by Roman historiographers and imperial propagandists to relate Eastern, “Persian,” campaigns led by Roman generals and emperors to the glorious antecedent of Alexander’s war against the Achaemenid Empire. The chapter highlights the political connotations of the image of Alexander as a kosmokrator in the mid- sixth century. Through this peculiar characterization of Alexander, the Syriac author not only expressed his anti-Sasanian feelings, which culminate in Alexander’s prophecy about the imminent collapse of the Sasanian Empire, but also criticized Justinian for his inability to repeat Alexander’s glorious deeds against the Persians and for his poor achievements in the conflict against the Sasanian enemy. In the Neṣḥānā the figure of Alexander is thus a nemesis of the Byzantine ruler. The chapter also notes the parallel between the Neṣḥānā and the Julian Romance, drawing attention to similarities between the characterizations of Alexander and Jovian in the two works—both of which criticize Justinian.
Alexander, the Danielic Visions, and the Gate against Gog and Magog
Authors: Tesei Tommaso
Published: November 2023

This chapter analyzes the peculiar and unprecedented characterization of Alexander as a pious (Christian) prophet-king and as the founder of the Roman Empire, envisaged as an eschatological agent. It argues that the figure of the Christian, apocalyptic Alexander in the Syriac work is rooted in the hermeneutics of the Danielic prophecies (Dan 2, 7, and 8) developed by Christians in both the Byzantine and Sasanian empires to situate the two empires in the framework of God’s plan for human salvation. The chapter emphasizes the parallels between the Neṣḥānā and the conceptualization of Alexander’s kingdom in Aphrahat’s (d. 345 ce) hermeneutic of Daniel. Finally, the chapter argues that a better understanding of the ideology and concepts behind the elaboration of the Syriac Alexander helps the reader to better understand the development of the story of Alexander’s eschatological gate. It demonstrates that some main features of the episode of the gate are embedded with a symbolism that relates to the Neṣḥānā author’s readings of the Danielic prophecies and to his views on the role of Alexander’s empire in sacred history.
Alexander’s Horns
Authors: Tesei Tommaso
Published: November 2023

This chapter analyzes the first part of the prayer that Alexander addresses to God at the beginning of the Syriac work, with special attention to the motif of Alexander’s horns in the Neṣḥānā. This motif emerges from ancient iconographic representations of Alexander crowned with ram horns—as in the effigies of the Greco-Egyptian god Zeus-Ammon. Unlike late antique Christians, who typically displayed hostility toward this pagan symbolism, the author of the Neṣḥānā Christianizes the image of the horned Alexander by reading it through the lens of biblical texts—including the Book of Daniel. The author uses the motif of Alexander’s horns to formulate an innovative hermeneutic of the Danielic vision of the ram and the he-goat in Daniel 8. This hermeneutic results in the attribution of an apocalyptic value to the ancient horn symbolism. The chapter argues that this literary operation is related to the author’s willingness to address contemporary political circumstances, especially Byzantine-Sasanian relationships. Through a sophisticated combination of biblical and Classical traditions, the Syriac author transforms the ancient representation of the horned Alexander into an element of his anti-Sasanian polemic.
Anxiety and depression in rheumatoid arthritis patients: prevalence, risk factors and consistency between the Hospital Anxiety and Depression Scale and Zung’s Self-rating Anxiety Scale/Depression Scale
Authors: Cheng Lu , Gao Wenjia , Xu Yan , Yu Zhe , Wang Wen , Zhou Jun , Zang Yinshan
Published: November 2023

Objectives

The aim was to explore the prevalence and independent risk factors for anxiety and depression in RA patients and to assess the consistency between the hospital anxiety and depression scale (HADS) and Zung’s self-rating anxiety scale/depression scale (SAS/SDS).

Methods

In total, 160 RA patients and 60 healthy controls (HCs) were enrolled consecutively, and HADS and SAS/SDS were completed.

Results

The HADS-defined anxiety rate, HADS-defined depression rate, SAS-defined anxiety rate and SDS-defined depression rate were 36.9, 36.3, 29.4 and 29.4%, respectively, in RA patients, all of which were much higher in RA patients than in HCs (all P < 0.001). A relatively high consistency was observed between HADS-defined anxiety and SAS-defined anxiety (κ = 0.551, P < 0.001) and between HADS-defined depression and SDS-defined depression (κ = 0.563, P < 0.001) in RA patients. Interestingly, screened by multivariate logistic regression analyses, single/divorced/widowed marital status, swollen joint count, disease duration, ESR, physician’s global assessment (PhGA) and DAS28 were independently correlated with HADS-defined or SAS-defined anxiety risk in RA patients; meanwhile, female biological sex, single/divorced/widowed marital status, rural location, disease duration, PhGA and DAS28 were independently associated with HADS-defined or SDS-defined depression risk in RA patients.

Conclusion

Anxiety and depression are highly prevalent in RA patients and are independently correlated with single/divorced/widowed marital status and higher disease activity. In addition, the HADS presents a high consistency with the SAS/SDS with many fewer questions, which might be more suitable for long-term assessment of RA.
Individual and organizational effects of international mobility policy: Effects of Mexico’s Scholarship Program in nanotechnology
Authors: Tirado Mayra M
Published: November 2023

This paper addresses policy effects of international mobility in developing countries. It proposes a multilevel approach to study research training policies, specifically focusing on international mobility schemes as capacity-building instruments, where effects need to be identified at both individual and organizational levels. The paper asserts that current categorizations of country efforts to build a solid scientific base should consider transference of effects in domestic research contexts. Using a survey and interview-based study of a mobility policy in Mexico, and nanotechnology-related disciplines and sectors, this paper’s findings suggest that mobility policies are crucial in creating high-quality individual research skills, but that their impact on building domestic research capacity may be modest. This paper contributes to the evaluation literature on national research training programs and their influence on research capacity in two ways. First, it mobilizes a multilevel analytical approach to examine the effects of policies on individuals and organizations, offering a broader conceptualization of impact. Second, by introducing these individual and organizational effects, the paper provides insights into how effects are enacted and transferred.
Cultural variation in neural responses to social but not monetary reward outcomes
Authors: Blevins Elizabeth , Ko Michael , Park BoKyung , Qu Yang , Knutson Brian , Tsai Jeanne L
Published: November 2023

European Americans view high-intensity, open-mouthed ‘excited’ smiles more positively than Chinese because they value excitement and other high arousal positive states more. This difference is supported by reward-related neural activity, with European Americans showing greater Nucleus Accumbens (NAcc) activity to excited (vs calm) smiles than Chinese. But do these cultural differences generalize to all rewards, and are they related to real-world social behavior? European American (N = 26) and Chinese (N = 27) participants completed social and monetary incentive delay tasks that distinguished between the anticipation and receipt (outcome) of social and monetary rewards while undergoing Functional Magnetic Resonance Imaging (FMRI). The groups did not differ in NAcc activity when anticipating social or monetary rewards. However, as predicted, European Americans showed greater NAcc activity than Chinese when viewing excited smiles during outcome (the receipt of social reward). No cultural differences emerged when participants received monetary outcomes. Individuals who showed increased NAcc activity to excited smiles during outcome had friends with more intense smiles on social media. These findings suggest that culture plays a specific role in modulating reward-related neural responses to excited smiles during outcome, which are associated with real-world relationships.
Naturally occurring autoimmune disease in (NZB × NZW) F1 mice is correlated with suppression of MZ B-cell development due to aberrant B-cell receptor (BCR) signaling, which is exacerbated by exposure to inorganic mercury
Authors: Gill Randall F , Mathieu Patricia A , Lash Lawrence H , Rosenspire Allen J
Published: November 2023

Autoimmune diseases are multifactorial and include environmental as well as genetic drivers. Although much progress has been made in understanding the nature of genetic underpinnings of autoimmune disease, by comparison much less is understood regarding how environmental factors interact with genetics in the development of autoimmunity and autoimmune disease. In this report, we utilize the (New Zealand black × New Zealand white [NZB × NZW]) F1 mouse model of systemic lupus erythematosus (SLE). Mercury is a xenobiotic that is environmentally ubiquitous and is epidemiologically linked with the development of autoimmunity. Among other attributes of human SLE, (NZB × NZW) F1 mice spontaneously develop autoimmune-mediated kidney disease. It has been previously shown that if (NZB × NZW) F1 mice are exposed to inorganic mercury (Hg2+), the development of autoimmunity, including autoimmune kidney pathology, is accelerated. We now show that in these mice, the development of kidney disease is correlated with a decreased percentage of marginal zone (MZ) B-cells in the spleen. In Hg2+-intoxicated mice, kidney disease is significantly augmented, and matched by a greater decrease in MZ B-cell splenic percentages than found in control mice. In Hg2+- intoxicated mice, the decrease in MZ B-cells appears to be linked to aberrant B-cell receptor signal strength in transitory 2 (T2) B-cells, developmental precursors of MZ B-cells.
Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential
Authors: Chappell Todd C. , Maiello Kathleen G. , Tierney Allison J. , Yanagi Karin , Lee Jessica A. , Lee Kyongbum , Mace Charles R. , Bennett Clay S. , Nair Nikhil U.
Published: November 2023

Microbial derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have potential as new therapeutics to target drug resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low yield biosynthetic gene clusters in the genusStreptomyces. Here, we describe our efforts to improve yields of landomycins – angucycline family polyketides under investigation as cancer therapeutics – by a genetically modifiedStreptomyces cyanogenus136. After simplifying the extraction process fromS. cyanogenuscultures, we identified a wavelength at which the major landomycin products absorb in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram-positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram-negative bacteria that is likely mediated by exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced byStreptomyces, as well as the light-absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest.
Rediscovering theRete Ovarii: a secreting auxiliary structure to the ovary
Authors: Anbarci Dilara N. , McKey Jennifer , Levic Daniel S. , Bagnat Michel , Capel Blanche
Published: November 2023

Therete ovarii(RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.
A seven-sex species recognizes self and non-self mating-type via a novel protein complex
Authors: Yan Guanxiong , Ma Yang , Wang Yanfang , Zhang Jing , Cheng Haoming , Tan Fanjie , Wang Su , Zhang Delin , Xiong Jie , Yin Ping , Miao Wei
Published: November 2023

Although most species have two sexes, multisexual (or multi-mating type) species are also widespread. However, it is unclear how mating-type recognition is achieved at the molecular level in multisexual species. The unicellular ciliateTetrahymena thermophilahas seven mating types, which are determined by the MTA and MTB proteins. In this study, we found that both proteins are essential for cells to send or receive complete mating-type information, and transmission of the mating-type signal requires both proteins to be expressed in the same cell. We found that MTA and MTB form a mating-type recognition complex that localizes to the plasma membrane, but not to the cilia. Stimulation experiments showed that the mating-type-specific regions of MTA and MTB mediate both self- and non-self-recognition, indicating thatT. thermophilauses a dual approach to achieve mating-type recognition. Our results suggest that MTA and MTB form an elaborate multifunctional protein complex that can identify cells of both self and non-self mating types in order to inhibit or activate mating, respectively.

Impact statement

A giant multifunctional protein complex mediates mating-type recognition through a non-ligand-receptor mechanism in a multisexual species.
BioWiC: An Evaluation Benchmark for Biomedical Concept Representation
Authors: Rouhizadeh Hossein , Nikishina Irina , Yazdani Anthony , Bornet Alban , Zhang Boya , Ehrsam Julien , Gaudet-Blavignac Christophe , Naderi Nona , Teodoro Douglas
Published: November 2023

Due to the complexity of the biomedical domain, the ability to capture semantically meaningful representations of terms in context is a long-standing challenge. Despite important progress in the past years, no evaluation benchmark has been developed to evaluate how well language models represent biomedical concepts according to their corresponding context. Inspired by the Word-in-Context (WiC) benchmark, in which word sense disambiguation is reformulated as a binary classification task, we propose a novel dataset, BioWiC, to evaluate the ability of language models to encode biomedical terms in context. We evaluate BioWiC both intrinsically and extrinsically and show that it could be used as a reliable benchmark for evaluating context-dependent embeddings in biomedical corpora. In addition, we conduct several experiments using a variety of discriminative and generative large language models to establish robust baselines that can serve as a foundation for future research.
Milo2.0 unlocks population genetic analyses of cell state abundance using a count-based mixed model
Authors: Alice Kluzer , Marioni John C , Morgan Michael D
Published: November 2023

Cell type proportions vary between individuals and are heritable, as demonstrated by statistical genetic analysis of flow cytometry data [1,2]. Higher-resolution cell states can be identified by single-cell RNA-sequencing, the scalability of which now makes it applicable to population-scale cohorts. However, the integration of statistical genetic analysis of cell states using cohort-scale single-cell data requires appropriate algorithms to account for and model the genetic relationships and complex batch-processing inherent to these studies. We describe Milo2.0, which enables the discovery of cell state quantitative trait loci (csQTL), scaling to millions of cells across hundreds of individuals. We identify > 500 csQTLs across peripheral blood immune states and investigate their relationship with the genetic regulation of gene expression. Moreover, we colocalise immune csQTLs with human traits and identify links between immune regulators, cell state abundance and immune-mediated disease.
Use of Multiple Pharmacodynamic Measures to Deconstruct the Nix-TB Regimen in a Short-Course Murine Model of Tuberculosis
Authors: Lyons M.A. , Obregon-Henao A. , Ramey M.E. , Bauman A.A. , Pauly S. , Rossmassler K. , Reid J. , Karger B. , Walter N.D. , Robertson G.T.
Published: November 2023

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen (bedaquiline-pretomanid-linezolid [BPaL]) during the first three weeks of treatment at human equivalent doses. RS ratio, an exploratory pharmacodynamic (PD) marker of ongoingMycobacterium tuberculosisrRNA synthesis, to-gether with solid culture CFU and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness ofin vivosystems for preclinical TB regimen development.
Unsaturated fatty acid alters the immune response in non-small cell lung adenocarcinoma through regulation of HMGB1 trafficking
Authors: Cole-Skinner Breanna , Andre Nicole M. , Blankenheim Zachary , Root Kate , Simmons Glenn E.
Published: November 2023

Cancer cell evasion of the immune response is critical to cancer development and metastases. The ability of clinicians to kickstart the immune system to target these rogue cells is an ever-growing area of research and medicine. In this study, we delved into the relationship between lipid metabolism, High Mobility Group Box 1 protein (HMGB1), and immune regulation within non-small cell lung adenocarcinoma (NSCLC), shedding light on novel therapeutic avenues and potential personalized approaches for patients. We found that the expression of stearoyl CoA desaturase 1 (SCD1) was decreased in NSCLC tumors compared to normal tissues. This emphasized the critical role of lipid metabolism in tumor progression. Interestingly, monounsaturated fatty acid (MUFA) availability impacted the expression of programmed death receptor ligand −1 (PD-L1), a pivotal immune checkpoint target in lung cancer cells and immune cells, suggesting a novel approach to modulating the immune response. This study uncovered a complex interplay between HMGB1, SCD1, and PD-L1, influencing the immunological sensitivity of tumors. Our work underscores the importance of understanding the intricate relationships between lipid metabolism and immune modulation to develop more effective NSCLC treatments and personalized therapies. As we continue to explore these connections, we hope to contribute to the ever-evolving field of cancer research, improving patient outcomes and advancing precision medicine in NSCLC.
Covert RNA viruses in medflies differ in their mode of transmission and tissue tropism
Authors: Hernández-Pelegrín Luis , Huditz Hannah-Isadora , García-Castillo Pablo , de Ruijter Norbert C.A. , van Oers Monique M. , Herrero Salvador , Ros Vera I.D.
Published: November 2023

Numerous studies have demonstrated the presence of covert viral infections in insects. These infections can be transmitted in insect populations via two main routes: vertical from parents to offspring, or horizontal between nonrelated individuals. Thirteen covert RNA viruses have been described in the Mediterranean fruit fly (medfly). Some of these viruses are established in different laboratory-reared and wild medfly populations, although variations in the viral repertoire and viral levels have been observed at different time points. To better understand these viral dynamics, we characterized the prevalence and levels of covert RNA viruses in two medfly strains, assessed the route of transmission of these viruses, and explored their distribution in medfly adult tissues. Altogether, our results indicated that the different RNA viruses found in medflies vary in their preferred route of transmission. Two iflaviruses and a narnavirus are predominantly transmitted through vertical transmission via the female, while a nodavirus and a nora virus exhibited a preference for horizontal transmission. Overall, our results give valuable insights into the viral tropism and transmission of RNA viruses in the medfly, contributing to the understanding of viral dynamics in insect populations.
Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1
Authors: Xu Cheng , Kleinschmidt Holly , Yang Jianyu , Leith Erik , Johnson Jenna , Tan Song , Mahony Shaun , Bai Lu
Published: November 2023

Despite the unique ability of pioneer transcription factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called ChIP-ISO to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1. Combining ChIP-ISO within vitroand neural network analyses, we find that 1) FOXA1 binding is strongly affected by co-binding TFs AP-1 and CEBPB, 2) FOXA1 and AP-1 show binding cooperativityin vitro, 3) FOXA1’s binding is determined more by local sequences than chromatin context, including eu-/heterochromatin, and 4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.
Cytoneme-mediated intercellular signaling in keratinocytes essential for epidermal remodeling
Authors: Wang Yi , He Qingan , Has Oliver , Forouzesh Kiarash , Eom Dae Seok
Published: November 2023

The skin, the largest organ, functions as a primary defense mechanism. Epidermal stem cells supply undifferentiated keratinocytes that differentiate as they migrate toward the outermost skin layer. Although such a replenishment process is disrupted in various human skin diseases, its underlying mechanisms remain elusive. With high-resolution live imaging and in vivo manipulations, we revealed that Notch signaling between keratinocytes is mediated by signaling filopodia called cytonemes and is essential for proper keratinocyte differentiation and proliferation. Inhibiting keratinocyte cytonemes reduced Notch expression within undifferentiated keratinocytes, leading to abnormal differentiation and hyperproliferation, resembling human skin disease phenotypes. Overproduction of Interleukin (IL)-17 signal, associated with skin diseases likepsoriasis, induces psoriatic phenotypes via cytonemes in zebrafish. Our study suggests that intercellular signaling between keratinocytes through cytonemes is critical for epidermal maintenance, and its misregulation could be an origin of human skin diseases.