bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combiningin silicoandin vitroapproaches to understand the involvement of methylerythritol 4-phosphate and shikimate pathways inAgrobacterium tumefaciensfor enhanced coenzyme Q10 production
Authors: Yadav Karuna , Arora Devender , Jatain Indu , Dubey Kashyap Kumar , Dhaka Namrata , Kaur Inderjeet , Adlakha Nidhi 
Published: May 2023

AbstractAimsTo perform an integrated comparative analysis of metabolic pathway to understand coenzyme Q10 (CoQ10) production in Agrobacterium tumefaciens.Methods and resultsComparative analysis of the CoQ10 metabolic pathway in 10 organisms using a genome to KEGG orthology program (G2KO) and the KEGG database elucidated the completeness of the production pathway in A. tumefaciens. The specific roles of the key precursors and the enzymes in the metabolic network were subsequently confirmed using pathway inhibitors and enhancers. While the use of fosmidomycin and glyphosate was found to inhibit CoQ10 production by 54.54% to 99%, the supplementation of polyprenyl pyrophosphate of the methylerythritol 4-phosphate pathway and 4-hydroxybenzoate precursor of the shikimate pathway did increse the production of CoQ10 by 2.3-fold.ConclusionsThe present study provides a comprehensive understanding of the CoQ10 biosynthetic pathway in A. tumefaciens, which would assist rational metabolic engineering strategies for augmenting CoQ10 biosynthesis.
Effects of starch sources varying in particle sizes on ruminal fermentation, nutrient flow, starch digestibility, and lactation performance of dairy cows
Authors: Shipandeni Maria N T , Paula Eduardo M , Esposito Giulia , Faciola Antonio P , Raffrenato Emiliano 
Published: May 2023

Abstract
Cereal grains are the predominant starch source (SS) for dairy cows; however, starch digestibility varies greatly depending on source, grain processing, and potentially interactions between these factors. The objective was to study the effects of the interactions between SS, and particle sizes (PS) on ruminal fermentation, nutrient flow, starch digestibility, and lactation performance of dairy cows. Four ruminally cannulated multiparous Holstein cows were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Two SS (corn or sorghum) used in this study were either finely or coarsely ground (using a 1- or 4-mm screen sieve). Digesta flow was quantified using the reticular sampling technique, applying the triple-marker method. Data were analyzed using the GLIMMIX procedure of SAS version 9.3 (SAS Institute Inc., Cary, NC, USA). For ruminal pH, data were analysed with time as repeated measure. There were no interactions between SS and PS on production or intake, flow, and digestibility of nutrients. Dry matter intake was greater for the corn diet compared to the sorghum diet (25.15 vs. 21.98 kg/d), which consequently affected nutrient intake, however, PS did not affect intake. Milk yield was not affected by SS; however, it was greater for cows fed fine grains than cows fed coarser grains (25.32 vs. 23.16 kg/d). Milk fat and milk protein were not affected by SS or PS. Interactions (SS × PS) were observed for ruminal pH, reticular pH, and volatile fatty acids (VFA) concentrations but not for ruminal NH3–N concentration. Ruminal and reticular pH were greater for sorghum when coarsely ground and the total VFA concentration was decreased, compared to coarse corn and fine sorghum; however, coarsely grinding corn did not affect ruminal or reticular pH nor VFA concentration. Acetate concentration was lower for corn when finely ground; however, finely grinding sorghum did not affect acetate. Decreasing PS increased ruminal digestibility of starch (87.18% vs. 83.43%), reduced the flow of starch to the reticulum (0.79 vs. 0.96 kg/d) but decreased neutral detergent fiber digestibility in the rumen (30.23% vs. 34.88%). Although SS were differently affected by processing, the effects of PS on production, intake, flow, and digestibility of nutrients were observed regardless of the SS. Furthermore, the effects of decreasing PS on pH and VFA concentrations were more pronounced in sorghum compared to corn.
Children, Sexual Abuse and the Emotions of the Community Health Practitioner in England and Wales, 1970-2000
Authors: Beecher Ruth 
Published: May 2023

Abstract
A survivor of child sexual abuse felt that doctors missed opportunities to notice her distress when, at fourteen, she had an unexplained illness that lasted for a year. The cause, she wrote, was “explained by Doctors as psychological, but nobody questioned further. WHY??? … If adults don’t listen[,] then we have no one to turn to.” For decades, community health practitioners have been identified as an important group in protecting children from maltreatment, but survivor testimony and agency statistics demonstrate that they rarely receive verbal disclosures or recognize the physical or behavioural warning signs of sexual abuse. The accounts we have of the 1980s tell of swiftly heightening professional awareness, followed by a visceral backlash in the latter part of the decade that discouraged practitioners from acting on their concerns. This article uses trade and professional journals, training materials, textbooks, and new oral histories to consider why community-based doctors and nurses have struggled to notice and respond to the sexually abused child. It will argue that the conceptual model of child sexual abuse that community health practitioners encountered in the workplace encouraged a mechanical and procedural response to suspicions of abuse. In a highly gendered and contested workplace, practitioners’ feelings about how survivors, non-abusing family members, and perpetrators should be understood were rarely debated in training or in practice. The emotional cost to the practitioners of engagement with sexual abuse, and their need for spaces of reflexivity and structures of support, were ignored.
Postoperative alpha angle seems to be important for the achievement of clinical significance at a minimum 5-year follow-up after primary hip arthroscopy
Authors: Gürsan Onur , Hapa Onur , Matsuda Dean K , Aydemir Selahaddin , Çeltik Mustafa , Cici Hakan , Acan Ahmet Emrah 
Published: May 2023

ABSTRACTThe purpose of the present study was to clarify whether there is an association of postoperative alpha value with functional scores or progression of osteoarthritis at X-rays at the midterm after arthroscopic treatment of femoroacetabular impingement (FAI) syndrome with femoral osteoplasty, labral repair or debridement and rim trimming. A retrospective review of prospectively gathered data from 2013 to 2017 was performed. All patients who underwent first-time unilateral hip arthroscopy for FAI resection with 5-year follow-up were included. Patient-reported outcomes included the modified Harris Hip Score (mHHS) and Visual Analog Scale for Pain (Pain VAS). The progression of osteoarthritis (Tönnis grade) and radiological parameters (alpha angle, lateral center-edge angle [LCEA] and head-neck offset) were evaluated. A receiver operating characteristic (ROC) analysis was used to evaluate the correlation between significant variables and achievement of patient-acceptable symptomatic state (PASS) and degree of osteoarthritis. We identified 52 patients with a minimum 5-year follow-up (average, 6.7 years). The average patient age was 33.9 ± 11.5 years. There were 19 (36.5%) female patients. The mHHS improved from 60.1 ± 13.4 before surgery to 86.8 ± 14 after surgery (P &lt; 0.001). The Pain VAS decreased from 6.21 before surgery to 2 after surgery (P &lt; 0.001). Overall, 69% achieved the PASS for mHHS. The ROC curve for postoperative alpha angle demonstrated acceptable discrimination between patients achieving a fifth-year PASS value and those who did not have an area under the curve of 0.72. Patients having a postoperative alpha angle of ≤48.3° achieved the fifth-year PASS value at a significantly higher rate than patients having a postoperative alpha angle of &gt;48.3° (P = 0.002). The postoperative alpha angle is a predictor of the achievement of the fifth-year PASS value for the mHHS. A threshold of ≤48.3° had a sensitivity of 0.75 and a specificity of 0.69 to predict positivity.Level of evidence IV
High-resolution and analytical electron microscopy in a liquid flow cell via gas purging
Authors: Pivak Yevheniy , Park Junbeom , Basak Shibabrata , Eichel Rüdiger-Albert , Beker Anne , Rozene Alejandro , Pérez Garza Héctor Hugo , Sun Hongyu 
Published: May 2023

Abstract
Liquid-phase transmission electron microscopy (LPTEM) technique has been used to perform a wide range of in situ and operando studies. While most studies are based on the sample contrast change in the liquid, acquiring high qualitative results in the native liquid environment still poses a challenge. Herein, we present a novel and facile method to perform high-resolution and analytical electron microscopy studies in a liquid flow cell. This technique is based on removing the liquid from the observation area by a flow of gas. It is expected that the proposed approach can find broad applications in LPTEM studies.
Association of nativity with survival among adults with hepatocellular carcinoma
Authors: Zhou Kali , Song Ziwei , Rostomian Nairi , Dodge Jennifer L , Stern Mariana C , Setiawan V Wendy , Terrault Norah A , Cockburn Myles G , Liu Lihua 
Published: May 2023

Abstract

Introduction
Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis.

Methods
We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity–specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients.

Results
A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients.

Conclusion
Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed.
Tucatinib promotes immune activation and synergizes with programmed cell death–1 and programmed cell death–ligand 1 inhibition in HER2-positive breast cancer
Authors: Li Ran , Sant Sneha , Brown Emmaline , Caramia Franco , Nikolic Bronte , Clarke Kylie , Byrne Ann , Lara Gonzalez Luis E , Savas Peter , Luen Stephen J , Teo Zhi Ling , Virassamy Balaji , Neeson Paul J , Darcy Phillip K , Loi Sherene 
Published: May 2023

Abstract

Background
Programmed cell death–1 (PD-1) and programmed cell death–ligand 1 (PD-L1) inhibitors have poor efficacy in patients with trastuzumab-resistant advanced HER2-positive breast cancer. Tucatinib is a potent, selective anti-HER2 tyrosine kinase inhibitor with proven clinical benefit in the advanced setting in patients with trastuzumab resistance. We investigated if tucatinib can alter the tumor microenvironment and if this could be harnessed for therapeutic efficacy.

Methods
We investigated the antitumor efficacy and contribution of the immune response of tucatinib using 2 immunocompetent, HER2-positive murine breast cancer models (trastuzumab-sensitive H2N113; trastuzumab-resistant Fo5) and the efficacy of tucatinib with trastuzumab and PD-1 or PD-L1 checkpoint inhibitors.

Results
In both models, tucatinib statistically significantly inhibited tumor growth and demonstrated dose-dependent efficacy. Ex vivo analysis by flow cytometry of tumor-infiltrating lymphocytes in mice treated with tucatinib showed increased frequency, higher proliferation, and enhanced effector function of CD8+ effector memory T cells. Tucatinib treatment also increased frequency of CD8+PD-1+ and CD8+TIM3+ T cells, CD49+ natural killer cells, monocytes, and major histocompatibility complex II expression on dendritic cells and macrophages and a decrease in myeloid-derived suppressor cells. Gene expression analysis revealed statistically significant enrichment in pathways associated with immune activation, type I and II interferon response, adaptive immune response, and antigen receptor signaling. In vivo, tucatinib and α-PD-L1 or α-PD-1 demonstrated statistically significantly increased efficacy and improved survival of mice compared with tucatinib alone.

Conclusion
Tucatinib modulates the immune microenvironment favorably, and combination treatment with α-PD-L1 or α-PD-1 demonstrated increased efficacy in preclinical HER2-positive tumor models. These findings provide a rationale for investigation of tucatinib and immune checkpoint inhibition in the clinic.
Effect of Neonatal Abstinence Syndrome Treatment Status and Maternal Depressive Symptomatology on Maternal Reports of Infant Behaviors
Authors: Heller Nicole A , Logan Beth A , Shrestha Hira , Morrison Deborah G , Hayes Marie J 
Published: May 2023

Abstract

Objective
The objective of this study is to investigate the effects of maternal perinatal depression symptoms and infant treatment status for neonatal abstinence syndrome (NAS) on maternal perceptions of infant regulatory behavior at 6 weeks of age.

Methods
Mothers and their infants (N = 106; 53 dyads) were recruited from a rural, White cohort in Northeast Maine. Mothers in medication-assisted treatment (methadone) and their infants (n = 35 dyads) were divided based on the infant’s NAS pharmacological treatment (n = 20, NAS+ group; n = 15, NAS− group) and compared with a demographically similar, nonexposed comparison group (n = 18 dyads; COMP group). At 6 weeks postpartum, mothers reported their depression symptoms Beck Depression Inventory—2nd Edition) and infant regulatory behaviors [Mother and Baby Scales (MABS)]. Infant neurobehavior was assessed during the same visit using the Neonatal Network Neurobehavioral Scale (NNNS).

Results
Mothers in the NAS+ group showed significantly higher depression scores than the COMP group (p &lt; .05) while the NAS− group did not. Across the sample, mothers with higher depression scores reported higher infant “unsettled-irregularity” MABS scores, regardless of group status. Agreement between maternal reports of infant regulatory behaviors and observer-assessed NNNS summary scares was poor in both the NAS+ and COMP groups.

Conclusions
Postpartum women in opioid recovery with infants requiring pharmacological intervention for NAS are more at risk for depression which may adversely influence their perceptions of their infants’ regulatory profiles. Unique, targeted attachment interventions may be needed for this population.
Auxin as an architect of the pectin matrix
Authors: Jobert François , Yadav Sandeep , Robert Stéphanie 
Published: May 2023

Abstract
Auxin is a versatile plant growth regulator that triggers multiple signalling pathways at different spatial and temporal resolutions. A plant cell is surrounded by the cell wall, a complex and dynamic network of polysaccharides. The cell wall needs to be rigid to provide mechanical support and protection and highly flexible to allow cell growth and shape acquisition. The modification of the pectin components, among other processes, is a mechanism by which auxin activity alters the mechanical properties of the cell wall. Auxin signalling precisely controls the transcriptional output of several genes encoding pectin remodelling enzymes, their local activity, pectin deposition, and modulation in different developmental contexts. This review examines the mechanism of auxin activity in regulating pectin chemistry at organ, cellular, and subcellular levels across diverse plant species. Moreover, we ask questions that remain to be addressed to fully understand the interplay between auxin and pectin in plant growth and development.
Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SYS6006, as a fourth-dose booster following three doses of inactivated vaccines in healthy adults: an open-labeled Phase 1 trial
Authors: Gui Yuzhou , Cao Ye , He Jiajin , Zhao Chunyang , Zheng Wei , Qian Ling , Cheng Jie , Yu Chengyin , Yu Chen , Lou Kun , Liu Gangyi , Jia Jingying 
Published: May 2023

Abstract
The continuous emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines. Here, we report an open-labeled Phase I clinical trial of a modified mRNA vaccine (SYS6006) as a fourth-dose booster in healthy adults. Eighteen eligible participants, who had completed three doses of inactivated COVID-19 vaccines, received a fourth boosting dose of SYS6006-20 μg. Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity. The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein (RBD) antibodies of the Omicron strain (BA.2 and BA.4/5) in serum; titers of neutralizing antibodies against pseudovirus of the Omicron strain (BA.2 and BA.4/5). The secondary endpoint was the incidence of adverse events within 30 days after the boosting. The exploratory endpoint was the cellular immune responses (interferon gamma, IFN-γ). This trial was registered with the Chinese Clinical Trial Registry website. No serious adverse events were reported within 30 days after vaccination. No Grade 3 fever or serious adverse event was reported in the SYS6006 group. Notably, SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies (&gt;90 days) compared with the convalescent group (P &lt; 0.0001) against Omicron strain (BA.2 and BA.4/5). Besides, higher positive spots of T-cell-secreting IFN-γ were observed in the SYS6006 group than those in the convalescent group (P &lt; 0.05). These data demonstrated that SYS6006 was well tolerated and highly immunogenic, generating a stronger and more durable immune response against different variants of SARS-CoV-2.
Testing super-eddington accretion on to a supermassive black hole: reverberation mapping of PG 1119+120
Authors: Donnan Fergus R , Hernández Santisteban Juan V , Horne Keith , Hu Chen , Du Pu , Li Yan-Rong , Xiao Ming , Ho Luis C , Aceituno Jesús , Wang Jian-Min , Guo Wei-Jian , Yang Sen , Jiang Bo-Wei , Yao Zhu-Heng 
Published: May 2023

ABSTRACT
We measure the black hole mass and investigate the accretion flow around the local (z = 0.0502) quasar PG 1119+120. Spectroscopic monitoring with Calar Alto provides H β lags and linewidths from which we estimate a black hole mass of log (M•/M⊙) = 7.0, uncertain by ∼0.4 dex. High cadence photometric monitoring over 2 yr with the Las Cumbres Observatory provides light curves in seven optical bands suitable for intensive continuum reverberation mapping. We identify variability on two time-scales. Slower variations on a 100-d time-scale exhibit excess flux and increased lag in the u′ band and are thus attributable to diffuse bound-free continuum emission from the broad-line region. Faster variations that we attribute to accretion disc reprocessing lack a u′-band excess and have flux and delay spectra consistent with either τ ∝ λ4/3, as expected for a temperature structure of T(R) ∝ R−3/4 for a thin accretion disc, or τ ∝ λ2 expected for a slim disc. Decomposing the flux into variable (disc) and constant (host galaxy) components, we find the disc SED to be flatter than expected with $f_{\nu } \sim \rm {const}$. Modelling the SED predicts an Eddington ratio of λEdd &gt; 1, where the flat spectrum can be reproduced by a slim disc with little dust extinction or a thin disc that requires more dust extinction. While this accretion is super-Eddington, the geometry is still unclear; however, a slim disc is expected due to the high radiation pressure at these accretion rates, and is entirely consistent with our observations.
MpoxRadar: a worldwide MPXV genomic surveillance dashboard
Authors: Nasri Ferdous , Kongkitimanon Kunaphas , Wittig Alice , Cortés Jorge Sánchez , Brinkmann Annika , Nitsche Andreas , Schmachtenberg Anna-Juliane , Renard Bernhard Y , Fuchs Stephan 
Published: May 2023

Abstract
The mpox virus (MPXV) is mutating at an exceptional rate for a DNA virus and its global spread is concerning, making genomic surveillance a necessity. With MpoxRadar, we provide an interactive dashboard to track virus variants on mutation level worldwide. MpoxRadar allows users to select among different genomes as reference for comparison. The occurrence of mutation profiles based on the selected reference is indicated on an interactive world map that shows the respective geographic sampling site in customizable time ranges to easily follow the frequency or trend of defined mutations. Furthermore, the user can filter for specific mutations, genes, countries, genome types, and sequencing protocols and download the filtered data directly from MpoxRadar. On the server, we automatically download all MPXV genomes and metadata from the National Center for Biotechnology Information (NCBI) on a daily basis, align them to the different reference genomes, generate mutation profiles, which are stored and linked to the available metainformation in a database. This makes MpoxRadar a practical tool for the genomic survaillance of MPXV, supporting users with limited computational resources. MpoxRadar is open-source and freely accessible at https://MpoxRadar.net.
Conformational dynamics of the RNA binding channel regulates loading and translocation of the DEAH-box helicase Prp43
Authors: Enders Marieke , Ficner Ralf , Adio Sarah 
Published: May 2023

Abstract
The DEAH-box helicase Prp43 has essential functions in pre-mRNA splicing and ribosome biogenesis, remodeling structured RNAs. To initiate unwinding, Prp43 must first accommodate a single-stranded RNA segment into its RNA binding channel. This allows translocation of the helicase on the RNA. G-patch (gp) factors activate Prp43 in its cellular context enhancing the intrinsically low ATPase and RNA unwinding activity. It is unclear how the RNA loading process is accomplished by Prp43 and how it is regulated by its substrates, ATP and RNA, and the G-patch partners. We developed single-molecule (sm) FRET reporters on Prp43 from Chaetomium thermophilum to monitor the conformational dynamics of the RNA binding channel in Prp43 in real-time. We show that the channel can alternate between open and closed conformations. Binding of Pfa1(gp) and ATP shifts the distribution of states towards channel opening, facilitating the accommodation of RNA. After completion of the loading process, the channel remains firmly closed during successive cycles of ATP hydrolysis, ensuring stable interaction with the RNA and processive translocation. Without Pfa1(gp), it remains predominantly closed preventing efficient RNA loading. Our data reveal how the ligands of Prp43 regulate the structural dynamics of the RNA binding channel controlling the initial binding of RNA.