bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep diving off the ‘Cosmic Cliffs’: previously hidden outflows in NGC 3324 revealed by JWST
Authors: Reiter Megan , Morse Jon A , Smith Nathan , Haworth Thomas J , Kuhn Michael A , Klaassen Pamela D
Published: October 2022

We present a detailed analysis of the protostellar outflow activity in the massive star-forming region NGC 3324, as revealed by new Early Release Observations (EROs) from the James Webb Space Telescope (JWST). Emission from numerous outflows is revealed in narrow-band images of hydrogen Paschen α (Paα) and molecular hydrogen. In particular, we report the discovery of 24 previously unknown outflows based on their H2 emission. We find three candidate driving sources for these H2 flows in published catalogues of young stellar objects (YSOs), and we identify 15 infrared point sources in the new JWST images as potential driving protostars. We also identify several Herbig–Haro (HH) objects in Paα images from JWST; most are confirmed as jets based on their proper motions measured in a comparison with previous Hubble Space Telescope (HST) Hα images. This confirmed all previous HST-identified HH jets and candidate jets, and revealed seven new HH objects. The unprecedented capabilities of JWST allow the direct comparison of atomic and molecular outflow components at comparable angular resolution. Future observations will allow quantitative analysis of the excitation, mass-loss rates, and velocities of these new flows. As a relatively modest region of massive star formation (larger than Orion but smaller than starburst clusters), NGC 3324 offers a preview of what star formation studies with JWST may provide.
Demographics of z ∼ 6 quasars in the black hole mass–luminosity plane
Authors: Wu Jin , Shen Yue , Jiang Linhua , Bañados Eduardo , Fan Xiaohui , Ho Luis C , Vestergaard Marianne , Wang Feige , Wang Shu , Wu Xue-Bing , Yang Jinyi
Published: October 2022

We study the demographics of z ∼ 6 broad-line quasars in the black hole (BH) mass–luminosity plane using a sample of more than 100 quasars at 5.7 < z < 6.5. These quasars have well-quantified selection functions and nearly one-third of them also have virial BH masses estimated from near-IR spectroscopy. We use forward modelling of parametrized intrinsic distributions of BH masses and Eddington ratios, and account for the sample flux limits and measurement uncertainties of the BH masses and luminosities. We find significant differences between the intrinsic and observed distributions of the quantities due to measurement uncertainties and sample flux limits. There is also marginal evidence that the virial BH masses are susceptible to a positive luminosity-dependent bias (BH mass is overestimated when luminosity is above the average), and that the mean Eddington ratio increases with BH mass. Our models provide reliable constraints on the z ∼ 6 BH mass function at $M_{\rm BH}\gt 10^{8.5}\, M_\odot$, with a median 1σ uncertainty of ∼0.5 dex in abundance. The intrinsic Eddington ratio distribution of $M_{\rm BH}\gt 10^{8.5}\, M_\odot$ quasars can be approximated by a mass-dependent Schechter model, with a broad peak around log (Lbol/LEdd) ∼ −0.9. We also find that, at 4.5 ≲ z ≲ 6, the number densities of more massive BHs tend to decline more rapidly with increasing redshift, contrary to the trend at 2.5 ≲ z ≲ 4.5 reported previously.
Hylobates moloch(Primates: Hylobatidae)
Authors: Caspar Kai R , Yi Yoonjung
Published: October 2022

Hylobates moloch (Audebert, 1797), the Javan or silvery gibbon, is a pair-living small ape which is exclusively found in the western and central regions of the Indonesian island of Java. It represents the southernmost occurring species of the genus Hylobates and inhabits the canopy of tropical rainforests. It is foremost characterized by its long silvery-gray fur in combination with a lack of duet songs in mated pairs. Hylobates moloch is threatened by habitat loss as well as the illegal wildlife trade and is listed as “Endangered” (EN) by the IUCN Red List of Threatened Species.
A Phase I, Double-blind, Randomized, Placebo-controlled, Single Dose-escalation Study to Evaluate the Tolerability, and Safety of Cytisinicline in Adult Smokers
Authors: Jacobs Cindy , Fonseca Marlene , Rigotti Nancy A , Benowitz Neal , Clarke Anthony , Cain Dan
Published: October 2022

Introduction

Cytisinicline is a nicotinic acetylcholine receptor partial agonist marketed historically as oral tablets in Central and Eastern Europe as an aid to smoking cessation. Dosing and scheduled regimen for cytisinicline treatment is currently being redeveloped for market approval in the United States and elsewhere.

Aims and Methods

A phase 1, double-blind, randomized, placebo-controlled, single-ascending dose clinical trial was conducted under fasting conditions in healthy adults who were current daily (>10 cigarettes) smokers. Safety parameters for the identification of a maximum tolerated dose (MTD) and limited supportive pharmacokinetic assessments were evaluated. Ascending single oral doses of cytisinicline or placebo were administered to 9 cohorts, each comprised of eight unique participants (randomization: 6 cytisinicline; 2 placebo). Dose escalation to the next cohort was dependent upon the safety review of preceding cohorts. Dose levels tested were 6, 9, 12, 15, 18, 21, 24, 27, and 30 mg. Treatment-emergent adverse events (TEAEs) and clinically relevant changes in laboratory blood tests, vital signs, and 12-lead electrocardiograms were evaluated.

Results

Seventy-two participants completed the study (54 cytisinicline; 18 placebo). Nausea was the most common TEAE (10 participants [19%]). The MTD was defined as cytisinicline 30 mg based on gastrointestinal symptoms, predominantly vomiting (2 of 6 subjects, 33%). Maximum plasma concentration (observed Cmax) values appeared to plateau at higher dose levels (beyond 24 mg).

Conclusions

Single cytisinicline doses up to 30 mg were well tolerated and raised no new safety concerns in fasting adult smokers. An increased frequency of gastrointestinal symptoms defined the MTD at 30 mg.

Implications

The cytisinicline therapeutic dose being evaluated in phase 3 clinical trials is 3 mg, which is a 10-fold lower dose than the 30 mg MTD level for cytisinicline, resulting in an excellent safety margin.
Religious Life in African Societies
Authors: Manglos-Weber Nicolette D.
Published: October 2022

Just as European colonizers drew up arbitrary state borders in the “scramble for Africa” of the late 19th century, so have external authorities often imposed religious categories on African societies. Yet today, practicing and observing religion in the region is as much about challenging such distinctions as upholding them. African religious life is dynamic and pluralist, integrating three major currents of faith—Christianity, Islam, and African Indigenous traditions—and a diversity of subgroups and alternative or interstitial communities. It encompasses varied facets of practice, authority, identity, and place, and it demonstrates an ambivalent and contradictory relationship to modern nation-state politics. This chapter addresses these characteristics in turn, balancing broad themes and local particulars. It calls for paying closer attention to religion in African societies to better understand the significance of global religion, especially as it relates to the legacies of global imperialism and the challenges of religious pluralism.
Large-scale outflow structure and radiation properties of super-Eddington flow: Dependence on the accretion rates
Authors: Yoshioka Shogo , Mineshige Shin , Ohsuga Ken , Kawashima Tomohisa , Kitaki Takaaki
Published: October 2022

In order to evaluate the impacts made by super-Eddington accretors on their environments precisely, it is essential to guarantee a large enough simulation box and long computational time to avoid any artefacts from numerical settings as much as possible. In this paper, we carry out axisymmetric two-dimensional radiation hydrodynamic simulations around a 10 M⊙ black hole in large simulation boxes and study the large-scale outflow structure and radiation properties of super-Eddington accretion flow for a variety of black hole accretion rates, ${\dot{M}}_{\,\,\rm BH} = (110\!-\!380)L_{\rm Edd}/c^{\,\,2}$ (with LEdd being the Eddington luminosity and c being the speed of light). The Keplerian radius of the inflow material, at which centrifugal force balances with gravitational force, is fixed to 2430 Schwarzschild radii. We find that the mechanical luminosity grows more rapidly than the radiation luminosity with an increase of ${\dot{M}}_{\,\,\rm BH}$. When seen from a nearly face-on direction, especially, the isotropic mechanical luminosity grows in proportion to ${\dot{M}}_{\,\,\rm BH}^{\,\,2.7}$, while the total mechanical luminosity is proportional to ${\dot{M}}_{\,\,\rm BH}^{\,\,1.7}$. The reason for the former is that the higher ${\dot{M}}_{\,\,\rm BH}$ is, the more vertically inflated the disk surface becomes, which makes radiation fields more confined in the region around the rotation axis, thereby strongly accelerating outflowing gas. The outflow is classified into pure outflow and failed outflow, depending on whether the outflowing gas can reach the outer boundary of the simulation box or not. The fraction of the failed outflow decreases with a decrease of ${\dot{M}}_{\,\,\rm BH}$. We analyze physical quantities along each outflow trajectory, finding that the Bernoulli parameter (Be) is not a good indicator to discriminate between pure and failed outflows, since it is never constant because of continuous acceleration by radiation-pressure force. Pure outflow can arise, even if Be < 0 at the launching point.
Ambiguity among Partners: Understanding Power and Perception Under Conditions of Mutuality
Authors: Isett Kimberley R , Bryan Tara K , St. Clair-Sims Rebekah L
Published: October 2022

Power is a construct that is relevant anytime two actors come together. Typically power examinations have been focused on assessments among actors with asymmetrical power profiles. We argue existing characterizations of power are insufficient to understand perceptions of relationship quality when partners have a more balanced power profile. This is the case with an important class of partnerships—those between governments and philanthropic Foundations. We assessed power mutuality and its effects on relationship quality with a mixed methods approach, relying heavily on fuzzy-set qualitative comparative analysis techniques and interview data. Our findings point to new insights into those power relationships typically examined in the extant literature, those with asymmetry, as well as under condition of mutuality. With regard to asymmetrical power, we point to needed investigation into the role of intangible resources, such as knowledge and legitimacy, to achieve goals, rather than the predominant focus on financial and other tangible resources. With regard to conditions of mutuality, we illustrate that mutuality yields relational ambiguity in the relationship and results in partner tension. Furthermore, our study finds that under conditions of mutuality, resource contributions from the benefactor need to address instrumental organizational needs, not just needs that contribute to mission outcomes.
Potential welfare impacts from the continued spread of wild pigs
Authors: Holderieath Jason J , Crosby Michael K , McConnell T Eric
Published: October 2022

Wild pigs are spreading across the United States leaving potentially devastating crop losses in their wake. The majority of US corn, soybean, and wheat (approximately 85, 79, and 73%, respectively) and 6% of rice production are at risk in counties that do not currently have wild pigs. This work integrates the probability of a wild pig invasion to predict the welfare effects and price changes due to wild pigs spreading by using four predictive models linked to an equilibrium displacement model. Results show a decrease in total economic well-being of between approximately 54 and 350 million USD per year is possible. However, the outcomes for individual producers are overlooked. Some producers are much worse off, while others are slightly better off. This result demonstrates the importance of local-level analysis, as not all producers are affected the same way, and that distribution should be addressed in future work.
Understanding the Consequences of Moment-by-Moment Fluctuations in Mood and Social Experience for Paranoid Ideation in Psychotic Disorders
Authors: Orth Ryan D , Hur Juyoen , Jacome Anyela M , Savage Christina L G , Grogans Shannon E , Kim Young-Ho , Choe Eun Kyoung , Shackman Alexander J , Blanchard Jack J
Published: October 2022

Among individuals with psychotic disorders, paranoid ideation is common and associated with increased impairment, decreased quality of life, and a more pessimistic prognosis. Although accumulating research indicates negative affect is a key precipitant of paranoid ideation, the possible protective role of positive affect has not been examined. Further, despite the interpersonal nature of paranoid ideation, there are limited and inconsistent findings regarding how social context, perceptions, and motivation influence paranoid ideation in real-world contexts. In this pilot study, we used smartphone ecological momentary assessment to understand the relevance of hour-by-hour fluctuations in mood and social experience for paranoid ideation in adults with psychotic disorders. Multilevel modeling results indicated that greater negative affect is associated with higher concurrent levels of paranoid ideation and that it is marginally related to elevated levels of future paranoid ideation. In contrast, positive affect was unrelated to momentary experiences of paranoid ideation. More severe momentary paranoid ideation was also associated with an elevated desire to withdraw from social encounters, irrespective of when with familiar or unfamiliar others. These observations underscore the role of negative affect in promoting paranoid ideation and highlight the contribution of paranoid ideation to the motivation to socially withdraw in psychotic disorders.
Detection of Seiridium cardinale Causing Bark Cankers on Leyland Cypress (× Cupressocyparis leylandii) in Arizona
Authors: Hu J.
Published: October 2022

Leyland cypress (× Cupressocyparis leylandii) is an evergreen landscape tree that is fast growing and widely used to create windbreaks or privacy screening in Arizona. In Jul 2021, branch dieback and tree mortality were observed in Leyland cypress trees. Other symptoms include changed needle color, yellowing, wilting, branch decline, and longitudinal bark cankers on the stems and branches with resin exudates. Four branches with canker and resin exudates were collected for pathogen identification. Slow-growing fungal colonies on PDA had a dense and floccose appearance with a green or grayish-olive color in the center. Acervuli were formed on sterilized cypress twigs placed on water agar for 3 weeks under natural lighting provided by a nearby window with an eastern exposure (12 to 14 h photophase). Conidia were oblong-fusiform in shape and 21 to 28 × 8 to 11 μm (15 measurements). Conidia were five-septate with four dark brown media cells and two hyaline small end cells (1 μm long). These morphological characteristics putatively classified the fungus as Seiridium cardinale. ITS and BTUB DNA sequences confirmed the identification. To complete Koch's postulates, pathogenicity tests were conducted in the greenhouse on five 3-year-old Leyland cypress plants in 5-liter pots. This provides the first account of the occurrence of bark cankers caused by S. cardinale in Leyland cypress in Arizona.
Estrogen‐responsive cancer‐associated fibroblasts promote invasive property of gastric cancer in a paracrine manner via CD147 production
Authors: Bae Won Jung , Kim Seokhwi , Ahn Ji Mi , Han Jae Ho , Lee Dakeun
Published: October 2022

Estrogen signaling has been extensively studied, especially in cancers that express estrogen receptor alpha (ERα). However, little is known regarding the effect of estrogen on cancer‐associated fibroblasts (CAFs). Here, we explored the role of estrogen signaling of CAFs in gastric cancer (GC) progression. We investigated the phenotypic changes in CAFs upon 17β‐estradiol (E2) treatment using ERα‐negative/positive CAFs, and the conditioned media (CM) collected from these were compared with regard to cancer cell proliferation, migration, and invasion. A paracrine factor was found using a cytokine array and was confirmed using qRT‐PCR, western blotting, and enzyme‐linked immunosorbent assays. ERα‐CD147‐matrix metalloproteinase (MMP) axis was confirmed by knockdown experiments using specific siRNAs. We found that a subset of CAFs expressed ERα. ERα‐positive CAFs were responsive to E2, inducing ERα expression in a dose‐dependent manner. Although E2 did not induce the proliferation of ERα‐positive CAFs, the CM from E2‐bound ERα‐positive CAFs significantly promoted cancer cell migration and invasion. Cytokine array revealed that CD147 was induced in ERα‐positive CAFs upon E2 treatment; this was mediated via ERα. Increased CD147 upregulated MMP2 and MMP9 in CAFs, and also influenced cancer cells in a paracrine manner to increase MMPs and CD147 in cancer cells. High CD147 expression in tumor tissue was associated with a worse prognosis in GC patients. Our data suggest that estrogen signaling activation in CAFs and the byproduct CD147 are among the critical mediators between the interplay of CAFs and cancer cells to facilitate cancer progression.
Pseudocarcinomatous Hyperplasia Masquerading as a Well-Differentiated Squamous Cell Carcinoma Associated With Primary Cutaneous Anaplastic Large-Cell Lymphoma
Authors: LaTour Donn , Lee Michael P. , Gardner Jeffrey T. , Dao Harry , Kerstetter Justin , Elsensohn Ashley
Published: October 2022

Pseudocarcinomatous hyperplasia (PCH) is a reactive proliferation of the epidermis associated with CD30+ lymphoproliferative disorders. In this article, we report the case of a 42-year-old man who presented with a 10-year history of a solitary erythematous patch on the right thigh that progressed to an ulcerated, crusted plaque. Histologic examination revealed an infiltrate of atypical CD30+ lymphocytes consistent with primary cutaneous anaplastic large-cell lymphoma with overlying well differentiated keratinocyte hyperplasia akin to a well-differentiated invasive squamous cell carcinoma. This case demonstrates the phenomenon of pseudocarcinomatous hyperplasia mimicking features of invasive squamous cell carcinoma. It highlights the necessity of careful clinical correlation when diagnosing squamous cell carcinomas in younger patients on non–sun-exposed areas and the exclusion of accompanying known causes of pseudocarcinomatous hyperplasia.
Practice Patterns and Clinician Opinions for Treatment of Ocular Rosacea
Authors: Kaur Gurbani , Redd Travis K. , Seitzman Gerami D.
Published: October 2022

Purpose:

Management of ocular rosacea is challenged by the limited evidence-based systemic treatment guidelines and lack of elucidated mechanisms of treatment efficacy.

Methods:

We conducted an online survey of clinicians who regularly treat ocular rosacea to elicit their opinions on treatment algorithms and understanding of the treatment's primary mechanism of action. Descriptive statistics and univariate comparisons were reported.

Results:

One hundred thirty-two participants completed the online survey. Of the 132 respondents, 74% were cornea specialists. Most respondents (85%) favored systemic tetracyclines over macrolides. Providers' specialty training did not significantly influence preference between tetracyclines and macrolides for ocular rosacea management. Among tetracycline prescribers, there was no consensus regarding initial dosage and duration prescribing patterns. Most macrolide prescribers (88%) initiated a 3-week course of 1 gram of azithromycin weekly. Long-term management strategy for treatment-responsive patients varied: 46% preferred to half the initial dose, 29% discontinued pharmacotherapy, and 16% chronically pulse-dosed patients. Most tetracycline prescribers (90%) and macrolide prescribers (73%) postulate their chosen agents' primary mechanism of effect for ocular rosacea is anti-inflammatory. However, there was no consensus in identifying anti-inflammatory doses of either drug class. Furthermore, there is discordance between prescribers’ intended mechanistic effect with the selection of initial dosages for both tetracycline and macrolides for ocular rosacea.

Conclusions:

Among clinicians who commonly treat ocular rosacea, there is significant community equipoise regarding which dose of tetracycline is best for initial systemic treatment of this disease. In addition, a consensus understanding regarding mechanism of action of this treatment is lacking.
An Elderly Patient With Crouzon Syndrome Treated With Monobloc Distraction
Authors: Nakao Ko , Sakamoto Yoshiaki , Miwa Tomoru , Wakabayashi Kenichiro , Ishii Takenobu , Kishi Kazuo
Published: October 2022

Monobloc advancement by distraction osteogenesis is the treatment of choice in patients with syndromic craniosynostosis. This procedure is usually performed at 18 to 24 months/5 to 10 years of age. Herein, we present the case of a male patient with Crouzon syndrome who underwent monobloc advancement at the age of 62 years. Although the patient lived a normal life (employed, married, and being a father of a daughter), he visited our hospital for surgical improvement in facial esthetics. The patient underwent monobloc advancement by distraction osteogenesis. He was satisfied with the postoperative esthetic improvement and did not experience any major complications. This case highlights the fact that patients with syndromic craniosynostosis desire esthetic improvement and suggests that multidisciplinary treatment involving both the neuro and plastic surgeons is important in such cases.
AMPK phosphorylates NAMPT to regulate NAD
+
homeostasis under ionizing radiation
Authors: Liao Xiaoyu , Huang Xiaoke , Li Xin , Qiu Xuemei , Li Mi , Liu Rui , He Tao , Tang Qingfeng
Published: October 2022

Radiation-induced oral mucositis is the most common complication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD
+
) is vital for DNA damage repair under ionizing radiation, through functioning as either the substrate for protein poly(ADP-ribosyl)ation at DNA break sites or the cofactor for multiple DNA repair-related enzymes, which therefore can result in a significant consumption of cellular NAD
+
during DNA repair. Mammalian cells produce NAD
+
mainly by recycling nicotinamide via the salvage pathway, in which the rate-limiting step is governed by nicotinamide phosphoribosyltransferase (NAMPT). However, whether NAMPT is co-opted under ionizing radiation to timely fine-tune NAD
+
homeostasis remains elusive. Here we show that ionizing radiation evokes NAMPT activation within 30 min without apparent changes in its protein expression. AMPK rapidly phosphorylates NAMPT at S314 under ionizing radiation, which reinforces the enzymatic activity of NAMPT by increasing NAMPT binding with its substrate phosphoribosyl pyrophosphate (PRPP). AMPK-mediated NAMPT S314 phosphorylation substantially restores NAD
+
level in the irradiated cells and facilitates DNA repair and cell viability. Our findings demonstrate a new post-translational modification-based signalling route, by which cells can rapidly orchestrate NAD
+
metabolism to support DNA repair, thereby highlighting NAMPT as a potential target for the prevention of ionizing radiation-induced injuries.
Transcriptome analysis and mining of genes related to shade tolerance in foxtail millet (
Setaria italica
(L.) P. Beauv.)
Authors: Liu Dan , Cui Yanjiao , Zhao Zilong , Zhang Jing , Li Suying , Liu Zhengli
Published: October 2022

A stereo interplanting system with foxtail millet beneath chestnut trees is an effective planting method to raise the utilization of land in chestnut orchards, increase yields and improve quality of chestnut nuts. Consequently, exploration of genes involved in shade tolerance response in foxtail millet and breeding shade-tolerant varieties have become urgent issues. In this study, RNA-seq of leaf samples from two shade-tolerant varieties and three shade-intolerant varieties of foxtail millet at the booting stage was performed. Comparisons between the varieties revealed that 70 genes were commonly differentially expressed. Moreover, the ratio of net photosynthetic rate under shaded environment to that under light environment could be used as an indicator of shade tolerance. Subsequently, weighted gene co-expression network analysis was employed to construct a co-expression network and modules were correlated with this ratio. A total of 375 genes were identified as potentially relevant to shade tolerance, among which nine genes were also present in the 70 differentially expressed genes, which implied that they were good candidates for genes involved in shade tolerance. Our results provide valuable resources for elucidation of the molecular mechanisms underlying shade tolerance and will contribute to breeding of shade-tolerant foxtail millet that are adapted to the shaded environment under chestnut trees.
Higher phage virulence accelerates the evolution of host resistance
Authors: Wendling Carolin C. , Lange Janina , Liesegang Heiko , Sieber Michael , Poehlein Anja , Bunk Boyke , Rajkov Jelena , Goehlich Henry , Roth Olivia , Brockhurst Michael A.
Published: October 2022

Pathogens vary strikingly in their virulence and the selection they impose on their hosts. While the evolution of different virulence levels is well studied, the evolution of host resistance in response to different virulence levels is less understood and, at present, mainly based on observations and theoretical predictions with few experimental tests. Increased virulence can increase selection for host resistance evolution if the benefits of avoiding infection outweigh resistance costs. To test this, we experimentally evolved the bacterium
Vibrio alginolyticus
in the presence of two variants of a filamentous phage that differ in their virulence. The bacterial host exhibited two alternative defence strategies: (1) super infection exclusion (SIE), whereby phage-infected cells were immune to subsequent infection at the cost of reduced growth, and (2) surface receptor mutations (SRM), providing resistance to infection by preventing phage attachment. While SIE emerged rapidly against both phages, SRM evolved faster against the high- than the low-virulence phage. Using a mathematical model of our system, we show that increasing virulence strengthens selection for SRM owing to the higher costs of infection suffered by SIE immune hosts. Thus, by accelerating the evolution of host resistance, more virulent phages caused shorter epidemics.
Characterizing insect communities within thin-soil environments
Authors: McNamara Manning Katherine , Perry Kayla I. , Bahlai Christie A.
Published: October 2022

Natural thin-soil environments are those which have little to no soil accumulation atop hard substrates. Many of these natural thin-soil environments, such as alvars, rocky lakeshores or glades, cliffs and cliff bluffs, and barrens, are found in the Great Lakes Region of North America. Due to their ubiquity and ecosystem services they provide, characterizing insects in sensitive environments such as these is important. This study monitored insects in nine thin-soil sites, within three regions, on a 630 km latitudinal gradient in the Southeastern Great Lakes Region of North America from June - August 2019. Over 22,000 insect specimens collected were identified to order or family, and bee specimens were identified to genus or species. We found that overall insect community composition and biodiversity characteristics were similar between the three regions examined. However, the central region had higher taxonomic richness than the southern region. Although unique bee taxa were observed in each region, diversity metrics and community composition of bees were similar among sites. This study provides taxonomic information about the insect, particularly bees, and plant communities in thin-soil environments in this region, which could support conservation and management efforts.
Understanding water conservation vs. profligation traits in vegetable legumes through a physio-transcriptomic-functional approach
Authors: Fang Pingping , Sun Ting , Pandey Arun Kumar , Jiang Libo , Wu Xinyang , Hu Yannan , Cheng Shiping , Li Xiaofang , Xu Pei
Published: October 2022

Vegetable soybean and cowpea are related warm-season legumes showing contrasting leaf water use behaviors under similar root drought stresses, whose mechanisms are not well understood. Here we conducted an integrative phenomic-transcriptomic study on the two crops grown in a feedback irrigation system that enabled precise control of soil water contents. Continuous transpiration rate monitoring demonstrated that cowpea used water more conservatively under earlier soil drought stages, but tended to maintain higher transpiration under prolonged drought. Interestingly, we observed a soybean-specific transpiration rate increase accompanied by phase shift under moderate soil drought. Time-series transcriptomic analysis suggested a dehydration avoidance mechanism of cowpea at early soil drought stage, in which the VuHAI3 and VuTIP2;3 genes were suggested to be involved. Multifactorial gene clustering analysis revealed different responsiveness of genes to drought, time of day and their interactions between the two crops, which involved species-dependent regulation of the core clock genes. Gene network analysis identified two co-expression modules each associated with transpiration rate in cowpea and soybean, including a pair of negatively-correlated modules between species. Module hub genes, including the ABA-degrading gene GmCYP707A4 and the trehalose-phosphatase/synthase gene VuTPS9 were identified. Inter-modular network analysis revealed putative co-players of the hub genes. Transgenic analyses verified the role of VuTPS9 in regulating transpiration rate under osmotic stresses. These findings propose that species-specific transcriptomic reprograming in leaves of the two crops suffering similar soil drought was not only a result of the different drought resistance level, but a cause of it.
Awareness, Acceptance and Associated Factors of Human Papillomavirus Vaccine Among Parents of Daughters in Hadiya Zone, Southern Ethiopia: A Cross-Sectional Study
Authors: Larebo Yilma Markos , Elilo Legesse Tesfaye , Abame Desta Erkalo , Akiso Denebo Ersulo , Bawore Solomon Gebre , Anshebo Abebe Alemu , Gopalan Natarajan
Published: October 2022

Introduction

Human papillomavirus infections are the most prevalent sexually transmitted disease among women worldwide. Cervical cancer is the second most frequent disease worldwide in terms of incidence and mortality, and it is primarily responsible for fatalities in low- to middle-income nations, including Ethiopia. In the Hadiya Zone of Southern Ethiopia, the goal of this study is to determine parental knowledge about, acceptance of, and factors related to the human papillomavirus vaccine.

Methods

From November to December 2021, a community-based cross-sectional study would be conducted in Hadiya Zone among parents with daughters in the Zone. The study respondents would be chosen using a two-stage sampling technique from parents with a 9-14-year-old daughter. An interviewer-administered questionnaire would be used to collect data. For analysis, the data were entered into Epidata version 3.1 and exported to SPSS version 25. Variables with a p-value less than 0.25 in the bivariate analysis were transferred to multivariate analysis. A logistic regression model was applied to forecast the association between the predictor and outcome variables. Statistical significance was considered at a 0.05 p-value.

Results

The study showed that the overall acceptance of parents to vaccinate their daughter with HPV vaccination was 450 (84.9%). Parents of daughters having of male sex (AOR: 0.407; 95%CI: 0.221,0.748), having number of daughter’s one(AOR: 2.122; 95%CI: 1.221,3.685), government school type(AOR: 0.476;95%CI: 0.263,0.861), poor knowledge(AOR: 0.532;95%CI: 0.293,0.969) and negative attitude(AOR: 0.540;95%CI: 0.299,0.977) were discovered to have a strong correlation. Conclusion: This study found that there was a high level of parental acceptance; attitudes and knowledge about the HPV vaccine are significant in determining their intentions to vaccinate their daughter. Authorities in areas where cervical cancer incidence is at risk should plan and implement by providing health information regarding the human papillomavirus vaccination with an emphasis on raising community awareness.
Patient-specific Quality Assurance Failure Prediction with Deep Tabular Models
Authors: Levin R. , Aravkin A. Y. , Kim M.
Published: October 2022

Background

Patient-specific quality assurance (PSQA) is part of the standard practice to ensure that a patient receives the dose from intensity-modulated radiotherapy (IMRT) beams as planned in the treatment planning system (TPS). PSQA failures can cause a delay in patient care and increase workload and stress of staff members. A large body of previous work for PSQA failure prediction focuses on non-learned plan complexity measures. Another prominent line of work uses machine learning methods, often in conjunction with feature engineering. Currently, there are no machine learning solutions which work directly with multi-leaf collimator (MLC) leaf positions, providing an opportunity to improve leaf sequencing algorithms using these techniques.

Purpose

To improve patient safety and work efficiency, we develop a tabular transformer model based directly on the MLC leaf positions (without any feature engineering) to predict IMRT PSQA failure. This neural model provides an end-to-end differentiable map from MLC leaf positions to the probability of PSQA plan failure, which could be useful for regularizing gradient-based leaf sequencing optimization algorithms and generating a plan that is more likely to pass PSQA.

Method

We retrospectively collected DICOM RT PLAN files of 968 patient plans treated with volumetric arc therapy. We construct a beam-level tabular dataset with 1873 beams as samples and MLC leaf positions as features. We train an attention-based neural network FT-Transformer to predict the ArcCheck-based PSQA gamma pass rates. In addition to the regression task, we evaluate the model in the binary classification context predicting the pass or fail of PSQA. The performance was compared to the results of the two leading tree ensemble methods (CatBoost and XGBoost) and a non-learned method based on mean MLC gap.

Results

The FT-Transformer model achieves 1.44% Mean Absolute Error (MAE) in the regression task of the gamma pass rate prediction and performs on par with XGBoost (1.53 % MAE) and CatBoost (1.40 % MAE). In the binary classification task of PSQA failure prediction, FT-Transformer achieves 0.85 ROC AUC (with CatBoost and XGBoost achieving 0.87 ROC AUC and the mean-MLC-gap complexity metric achieving 0.72 ROC AUC). Moreover, FT-Transformer, CatBoost, and XGBoost all achieve 80% true positive rate while keeping the false positive rate under 20%.

Conclusions

We demonstrate that reliable PSQA failure predictors can be successfully developed based solely on MLC leaf positions. Our FT-Transformer neural network can reduce the need for patient rescheduling due to PSQA failures by 80% while sending only 20% of plans that would not have failed the PSQA for replanning. FT-Transformer achieves comparable performance with the leading tree ensemble methods while having an additional benefit of providing an end-to-end differentiable map from MLC leaf positions to the probability of PSQA failure.
Celiac dysbiosis does not transcend geographic boundaries
Authors: Colgan John J , Burns Michael B
Published: October 2022

Celiac disease is an autoimmune disorder of the small intestine in which gluten, an energy-storage protein found in wheat and other cereals, elicits an immune response that leads to villous atrophy. Despite a strong genetic component, celiac disease arises sporadically and at any age, leading us to hypothesize that changes in the microbiome influence celiac disease development and/or progression. Here, we pooled and computationally analyzed 16S data from 3 prior international studies that examined celiac disease and the microbiome. For our analysis, we combined the dada2 and PICRUSt 2 pipelines and a variety of data transformations that control for batch effects to determine whether any taxonomic or metabolic features were consistently associated with the celiac microbiome across the globe. Our results showed the celiac microbiome displays dysbiosis without a discernable pattern, which suggests perturbations in the celiac microbiome are a result of the disease rather than a cause. Data from PICRUSt 2 supported this conclusion and revealed connections between celiac disease and the metabolome that are supported by previous research examining dysbiotic microbiomes.

IMPORTANCE

Celiac disease is an autoimmune disorder that affects roughly 2% of the world’s population. Although the ultimate cause of celiac disease is unknown, many researchers hypothesize that changes to the intestinal microbiome play a key role in disease progression. If this is the case, it may be possible to design therapies that manipulate the microbiome to suppress celiac disease. Here, we analyzed pooled data from 3 different studies from across the globe that examined celiac disease and the microbiome to ascertain whether there exists a unique celiac microbiome that transcends geographic boundaries.
The MLL3/TP53/PIK3CA cancer driver mutations promote HIF1α-dependent recruitment and differentiation of pro-tumor ICOShiGITRhiBlimp-1+effector regulatory T cells in breast tumors
Authors: Boutet Marie , Nishitani Kenta , Erler Piril , Couturier Nicole , Zhang Zheng , Militello Anna Maria , De Miranda Marcelo Coutinho , Barbieux Emeline , Guillen Erik , Suzuki Masako , Sparano Joseph A. , Montagna Cristina , Guo Wenjun , Lauvau Gregoire
Published: October 2022

While essential gatekeepers of immune homeostasis, Foxp3+regulatory T (Treg) cells infiltrating tumors acquire distinct phenotypes and become highly immunosuppressive, promoting tumor immune escape and growth. How this occurs and relates to tumor-driver mutations is largely uncharacterized. Herein, we created a mouse mammary stem cell-based tumor model using CRISPR gene editing in which we introduced known human cancer-driver mutations. These included functional loss of the MLL3 histone methyltransferase and p53, and constitutive PI3-kinase activation, recapitulating the genetic makeup of aggressive breast cancers. We show that MLL3 loss fosters tumorigenesis by promoting the rapid establishment of an immunosuppressive microenvironment through induction of HIF1α, which increases the secretion of the chemokine CCL2 by tumor cells and the recruitment of higher numbers of Foxp3+Tregcells via CCR2. Greater infiltration of Tregcells also correlates with MLL3 downregulation and mutations in human breast cancer biopsies. Interestingly, HIF1α enforces the differentiation of tumor-infiltrating Tregcells into highly immunosuppressive ICOShiGITRhiBlimp-1hieffector Tregcells that enable rapid tumor escape. Monoclonal antibody targeting of ICOS or GITR inhibits tumorigenesis in most mice even two months after the cessation of treatment as well as the growth of established tumors, suggesting possible therapeutic opportunities for MLL3-mutant breast cancers.
Prostaglandin E2 production is required for phagocyte CXCR2-mediated skin host defense in obese and hyperglycemic mice
Authors: Klopsfenstein Nathan , Hibbs Kristin , Blackman Amondrea , Serezani C. Henrique
Published: October 2022

Poorly controlled glucose observed in obese individuals with diabetes is associated with a significantly increased risk of infection, particularly in the skin and soft tissues. Staphylococcus aureus is a significant cause of skin and soft tissue infections (SSTIs) in obese and hyperglycemic individuals with growing antibiotic resistance making these infections difficult to treat. However, the events that drive dysregulated skin host defense during hyperglycemia remain to be fully elucidated. Here we examined how the prostaglandin E2 (PGE2) threshold impacts tissue injury and host defense during methicillin-resistant S. aureus (MRSA) skin infection in obese and hyperglycemic mice. Our data show that obesity and hyperglycemia are accompanied by impaired expression of prostaglandin E synthase 1 and PGE2 production in infected skin. Restoration of PGE2 levels with the PGE analog misoprostol improved infection outcomes in obese and hyperglycemic mice in a manner dependent on E prostanoid 3-mediated cAMP inhibition. Topical misoprostol restored the levels of CXC chemokines and CXCR2+ monocyte and neutrophil recruitment. Here, we are unveiling a defective signaling program that culminates in inadequate CXCR2 phagocyte migration to the infected skin of obese and hyperglycemic mice. Furthermore, these data also lead to a novel drug repurposing opportunity to treat antibiotic-resistant pathogens in hyperglycemic conditions.
The variant catalogue pipeline: A workflow to generate a background variant library from Whole Genome Sequences
Authors: Correard Solenne , Abdallah Mohammed OE , Hewitson Brittany , Wasserman Wyeth W.
Published: October 2022

Today, several projects are working toward reducing inequities and improving health care for individuals affected with rare genetic diseases from diverse populations. One route to reduce inequities is to generate variant catalogues for diverse populations. To that end, we developed the variant catalogue pipeline, an open-source pipeline implemented in the Nextflow framework. The variant catalogue pipeline includes detection of single nucleotide variants, small insertions and deletions, mitochondrial variants, structural variants, mobile element insertions, and short tandem repeats. Sample and variant quality control, allele frequency calculation (for whole and sex-stratified cohorts) and annotation steps are also included, delivering vcf files with annotated variants and their frequency in the cohort. Successful application of the variant catalogue pipeline to 100 publicly available human genomes is described. We hope that, by making this pipeline available, more under-represented populations benefit from enhanced capacity to generate high-quality variant catalogues.
“Double-Effect” strategy against Triple-Negative Breast Cancer via a synergistic therapy of Magneto-mechanical Force enhancing NIR-II Hypothermal Ablation
Authors: Du Hui , Yang Fang , Yao Chenyang , Lv Wenhao , Peng Hao , Stanciu Stefan G. , Stenmark Harald A. , Song Young Min , Jiang Bo , Wu Aiguo
Published: October 2022

Triple-negative breast cancer (TNBC) is a form of breast cancer that is more aggressive and harder to treat than others, with a higher probability of relapse. Its highly efficient capabilities for migrating and invading other parts of the body together with the current lack of clinically established effective therapies account for a low survival rate. Thus, we propose the in-tandem use of two complementary therapeutic routes to effectively combat TNBC. Herein, a versatile magnetic-photothermal converter (MPC) is elaborately designed via integrating zinc-doped ferrite nanoparticles and polyethene glycol, synergistically enhanced through magneto-mechanical force (MMF) and near-infrared-II (NIR-II) hypothermal ablation, thereby displaying excellent therapeutic efficiency. Their combined use, which is less aggressive to the human body compared to conventional chemotherapeutic approaches, results in the splendid suppression of TNBC migration and invasion. Remotely controlling the MPCs by an external magnetic stimulus, results in cellular MMF effects that cause direct mechanical destruction to the cancer cell membrane, leading to its necrosis. Furthermore, the MMF disrupts intracellular lysosomes, thereby triggering the release of large amounts of protein hydrolases, which induce intracellular oxidative stress, and accelerate the induction of apoptosis. Complementing the therapeutic approach based on MMF, the excellent photothermal performance of the MPC in the NIR-II region (1064nm) is exploited to enable effective hypothermal ablation of the tumours, which can be achieved in deep tissue layers. The proposed multifunctional nanocomposites, together with the demonstrated “double effect” therapeutic approach, hold significant potential to pave the way for future cutting-edge weapons against the dreadful TNBC.
Nascent MSKIK peptide prevents or releases translation arrest in Escherichia coli
Authors: Ojima-Kato Teruyo , Nishikawa Yuma , Furukawa Yuki , Kojima Takaaki , Nakano Hideo
Published: October 2022

The insertion of the sequence encoding SKIK peptide adjacent to the M start codon of a difficult-to-express protein enhances protein production in Escherichia coli. In this report, we show that the increased production of the SKIK-tagged protein is not due to codon usage of the SKIK sequence. In addition, insertion of SKX, KKX, and AKX (X = G, L, H, Y, E, and F) at the N-terminus increased protein production. Furthermore, insertion of MSKIK just before the SecM arrest peptide (FSTPVWISQAQGIRAGP), which causes translational stalling on mRNA, greatly increased the production of the protein containing the SecM arrest peptide in the E. coli reconstituted cell-free protein synthesis system (PURE system). A similar phenomenon was observed for CmlA leader whose arrest is induced by chloramphenicol. These results suggest that the nascent MSKIK peptide prevents or releases translational stalling immediately following its generation during the translation process.
Basal but not complex motor control relies on interhemispheric structural connectivity after stroke
Authors: Paul Theresa , Wiemer Valerie M. , Hensel Lukas , Cieslak Matthew , Tscherpel Caroline , Grefkes Christian , Grafton Scott T. , Fink Gereon R. , Volz Lukas J.
Published: October 2022

Objective

While ample evidence highlights that the ipsilesional corticospinal tract (CST) plays a crucial role in motor recovery after stroke, very few studies have assessed cortico-cortical motor connections with inconclusive results. Given their unique potential to serve as structural reserve enabling motor network reorganization, the question arises whether cortico-cortical connections may facilitate motor control depending on CST damage.

Methods

Diffusion spectrum imaging (DSI) and a novel compartmentwise analysis approach were used to quantify structural connectivity between bilateral cortical core motor regions in chronic stroke patients. Basal and complex motor control were differentially assessed.

Results

Both basal and complex motor performance were correlated with structural connectivity between bilateral premotor areas and ipsilesional primary motor cortex (M1) as well as interhemispheric M1-M1 connectivity. While complex motor skills depended on CST integrity, a strong association between M1-M1 connectivity and basal motor control was observed independent of CST integrity especially in patients who underwent substantial motor recovery. Harnessing the informational wealth of cortico-cortical connectivity facilitated the explanation of both basal and complex motor control.

Interpretation

We demonstrate for the first time that distinct aspects of cortical structural reserve enable basal and complex motor control after stroke. In particular, recovery of basal motor control is supported via an alternative route through contralesional M1 and non-crossing fibers of the contralesional CST. Our findings help to explain previous conflicting interpretations regarding a vicarious or maladaptive role of the contralesional M1 and highlight the potential of structural connectivity of the cortical motor network as a biomarker post-stroke.