bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Baloxavir Marboxil in Influenza-infected Children 5–11 Years of Age: A Post Hoc Analysis of a Phase 3 Study
Authors: Baker Jeffery B. , Block Stanley L. , Cagas Steven E. , Macutkiewicz Laura Burleigh , Collins Colleen , Sadeghi Mitra , Sarkar Sriparna , Williams Sarah 
Published: August 2023

Background:
miniSTONE-2 (NCT03629184) was a global, phase 3, randomized, controlled study that investigated the safety and efficacy of single-dose baloxavir marboxil in otherwise healthy children 1–<12 years of age and showed a positive risk-benefit profile. This post hoc analysis evaluated the safety and efficacy of baloxavir versus oseltamivir in children 5–11 years old with influenza.

Methods:
Children received single-dose baloxavir or twice-daily oseltamivir for 5 days. Safety was the primary objective. Efficacy and virological outcomes included time to alleviation of symptoms, duration of fever and time to cessation of viral shedding by titer. Data were summarized descriptively.

Results:
Ninety-four children 5–11 years old were included (61 baloxavir and 33 oseltamivir). Baseline characteristics were similar between the groups. The incidence of adverse events was balanced and low in both treatment groups, with the most common being vomiting (baloxavir 5% vs. oseltamivir 18%), diarrhea (5% vs. 0%) and otitis media (0% vs. 5%). No serious adverse events or deaths occurred. Median (95% CI) time to alleviation of symptoms with baloxavir was 138.4 hours (116.7–163.4) versus 126.1 hours (95.9–165.7) for oseltamivir; duration of fever was comparable between groups [41.2 hours (23.5–51.4) vs. 51.3 hours (30.7–56.8), respectively]. Median time to cessation of viral shedding was shorter in the baloxavir group versus oseltamivir (1 vs. ≈3 days).

Conclusions:
Safety, efficacy and virological results in children 5–11 years were similar to those from the overall study population 1–<12 years of age. Single-dose baloxavir provides an additional treatment option for pediatric patients 5–11 years old with influenza.
Successful desensitization of a patient with hypersensitivity to pertuzumab: a case report
Authors: Lepage Violaine , Gratiaux Julian , Azzouz Brahim , Slimano Florian , Jouannaud Christelle , Parent Damien 
Published: August 2023

Abstract

Introduction:
Pertuzumab is a humanized monoclonal antibody used in the treatment of human epidermal growth factor receptor 2–positive early breast cancer. Its use can lead to a type-I hypersensitivity, which can be the result of an IgE-related reaction. This case describes a successful desensitization to pertuzumab in a patient diagnosed with a breast cancer.

Method:
A patient without a personal history of hypersensitivity and diagnosed with a human epidermal growth factor receptor 2–positive breast cancer was started on chemotherapy with association of trastuzumab, pertuzumab, and paclitaxel. While receiving the fourth cycle of pertuzumab, the patient developed a grade 2 hypersensitivity reaction resolved by the intravenous injection of dexchlorpheniramine and methylprednisolone. A premedication protocol has been setting up with a short desensitization protocol.

Results:
No adverse event occurred during the desensitization, which permits to continue pertuzumab at normal dose with a low occurrence of adverse events (spontaneous and favorable resolution). On analyzing the suspected adverse drug reaction, the event scored 10 and can found to be considered definite using the Naranjo Adverse Drug Reaction Probability Scale. This successful protocol of desensitization has helped to inhibit a hypersensitivity reaction. The monitoring showed the well-tolerance of the patient.

Conclusion:
This desensitization avoided a too early changing line treatment, which could have been deleterious. Very few cases of pertuzumab hypersensitivity occurred in France, and none benefited from a desensitization. This case illustrated the fact that rapid drug desensitization is possible, important and a simple opportunity to pursuit effective treatments.
“Associations between patient characteristics and unplanned or delayed discharges from geriatric rehabilitation: A retrospective chart review”
Authors: Perrella Andrew J , Karimi Arian , Reppas-Rindlisbacher Christina , Lee Justin , Wong Eric , Patterson Christopher 
Published: August 2023

Abstract
Returning home is considered an indicator of successful rehabilitation for community-dwelling older adults. However, the factors associated with unplanned discharge remain uncertain. This retrospective chart review included patients aged 65 years and older admitted to a geriatric rehabilitation unit from medical and surgical wards in an academic hospital. Patient characteristics and outcomes were abstracted from the electronic medical record. The primary outcome was unplanned discharge destination defined as anything other than return to patients’ pre-existing residence. The associations between patient variables and unplanned discharge destination were analyzed using Pearson chi-squared and univariate logistic regression. Of the 251 charts screened, 25 patients (10.0%) had an unplanned discharge destination, and 74 of the remaining 226 (32.7%) experienced a delayed discharge (beyond 20 days). Requiring assistance for activities of daily living (OR 2.80 [95% CI 1.17–7.47]), a diagnosis of chronic obstructive pulmonary disease (OR 4.04 [95% CI 1.63–9.71]), and lower serum albumin level (OR 1.67 [95% CI 1.06–2.72]) were associated with unplanned discharge. Variables commonly associated with worse outcomes such as age, cognitive scores, delirium, and number of comorbidities were not barriers to returning home and should therefore not be used on their own to limit access to geriatric rehabilitation.
Short Sleep and Insomnia Are Associated With Accelerated Epigenetic Age
Authors: Kusters Cynthia D.J. , Klopack Eric T. , Crimmins Eileen M. , Seeman Teresa E. , Cole Steve , Carroll Judith E. 
Published: August 2023

ABSTRACT

Objective
Short sleep and insomnia are each associated with a greater risk of age-related disease, which suggests that insufficient sleep may accelerate biological aging. We examine whether short sleep and insomnia alone or together relates to epigenetic age among older adults.

Methods
A total of 3795 men (46.3%) and women aged 56 to 100 years from the Health and Retirement Study were included. Insomnia was defined as reporting at least one insomnia symptom (difficulty falling asleep, waking up at night, or waking up too early in the morning) and feeling unrested when waking up most of the time. Those reporting <6 hours of bedtime were categorized as short sleepers. Three second- or third-generation epigenetic age acceleration clocks were derived from the 2016 Health and Retirement Study Venous Blood Study. The linear regression analysis was adjusted for age, sex, race/ethnicity, education, and obesity status.

Results
Insomnia and short sleep were associated with acceleration of GrimAge of 0.49 (95% confidence interval [CI] = 0.03–0.94 years; p = .04) and 1.29 (95% CI = 0.52–2.07 years; p = .002) years, respectively, as well as a faster pace of aging (DunedinPACE; 0.018 [95% CI = 0.004–0.033; p = .02] and 0.022 [95% CI = −0.004 to 0.048; p = .11]). Compared with healthy sleepers, individuals with the combination of short sleep and insomnia had an accelerated GrimAge (0.97 years; 95% CI = 0.07–1.87 years, p = .04) and a greater DunedinPACE (0.032; 95% CI = 0.003–0.060, p = .04).

Conclusions
Our findings indicate that short sleep, insomnia, and the combination of the two are linked to epigenetic age acceleration, suggesting that these individuals have an older biological age that may contribute to risk of comorbidity and mortality.
Facial Fat Graft Injection Reduces Asymmetry and Improves Forehead Contour in Early Infancy Apert Syndrome Patients
Authors: Raposo-Amaral Cassio E. , Menezes Priscila T. , Lemes Marcela V. , Medeiros Mateus L. , Raposo-Amaral Cesar A. , Ghizoni Enrico 
Published: August 2023

Background:
The objective of this study is to report the outcomes of a modified comprehensive Apert syndrome surgical protocol in which fat injection was performed during early infancy concurrent with postposterior vault distraction osteogenesis (PVDO) distractor removal.

Methods:
A retrospective study was performed on 40 consecutive young patients with Apert syndrome who underwent PVDO and subsequent distractor removal between 2012 and 2022. Of these 40 patients, 12 patients underwent facial fat injection concurrent with distractor removal to treat residual supraorbital bar recession as part of a modified comprehensive Apert syndrome surgical protocol. Preoperative and postoperative severity of recession and irregularity was graded from 1 to 3, with 1 being less severe and 3 being the most severe. Recession severity was correlated with the number and type of suture fusion. The complication rate was stratified via a Clavien-Dindo scale.

Results:
The average patient age was 14.3±5 months, with 5 males (41.6%) and 7 females (48.3%). The average hospital stay was 1.08 days. The average volume of free fat graft injection was 8.29±5 mL. According to the Likert scale, forehead morphology improved in 91.67% of the patients. Complete resolution of supraorbital bar recession was achieved in seven patients (58.33%), all of whom presenting a single suture synostosis. One patient with a cloverleaf skull presented a type IIIB complication.

Conclusions:
Facial fat grafting markedly reduces forehead asymmetry and improves forehead contour in Apert syndrome patients following PVDO. Total resolution of forehead recession directly correlated with a single suture fusion.
Gene drive and genetic sex conversion in the global agricultural pestCeratitis capitata
Authors: Meccariello Angela , Hou Shibo , Davydova Serafima , Fawcett James , Siddall Alexandra , Leftwich Philip T. , Krsticevic Flavia , Papathanos Philippos Aris , Windbichler Nikolai 
Published: August 2023

AbstractHoming-based gene drives are novel interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set of gene drives in a tephritid agricultural pest species, the Mediterranean fruit flyCeratitis capitata(medfly). Our results show that the medfly is highly amenable to homing-based gene drive strategies. By targeting the medflytransformergene, we also demonstrate two different mechanisms by which CRISPR-Cas9 gene drive can be coupled to sex conversion, whereby genetic females are transformed into fertile and harmless XX males. Given this unique malleability of sex determination, we modelled gene drive interventions that couple sex conversion and female sterility and found that such approaches could be effective and tolerant of resistant allele selection in the target population. Our results open the door for developing gene drive strains for the population suppression of the medfly and related tephritid pests by co-targeting female reproduction and shifting the reproductive sex ratio towards males. They demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.
Case report on lethal dog attacks on adult rhesus macaques (Macaca mulatta) in an anthropogenic landscape
Authors: Chakraborty Bidisha , Pithva Krishna , Mohanty Subham , McCowan Brenda 
Published: August 2023

AbstractFor nonhuman primates living in anthropogenic areas, predation by larger predators is relatively rare. However, smaller predators such as free-ranging as well as domesticated dogs can shape the socioecology of urban nonhuman primates, directly by attacking and predating upon them, or indirectly by modifying their activity patterns. Here, we describe 3 (2 potentially lethal) cases of dog attacks on adult rhesus macaques inhabiting an anthropogenic landscape in Northern India, and the circumstances surrounding these incidents. We discuss the importance of considering the presence of dogs while studying nonhuman primate populations across the anthropogenic gradient and its implications for understanding how human presence can directly and indirectly affect predator-prey relationship in these areas, as well as its potential role in modifying group social dynamics as well as in transmission of zoonotic agents.
tICA-Metadynamics for Identifying Slow Dynamics in Membrane Permeation
Authors: Oh Myongin , da Hora Gabriel C. A. , Swanson Jessica M. J. 
Published: August 2023

ABSTRACTMolecular simulations are commonly used to understand the mechanism of membrane permeation of small molecules, particularly for biomedical and pharmaceutical applications. However, despite significant advances in computing power and algorithms, calculating an accurate permeation free energy profile remains elusive for many drug molecules because it can require identifying the rate-limiting degrees of freedom (i.e., appropriate reaction coordinates). To resolve this issue, researchers have developed machine learning approaches to identify slow system dynamics. In this work, we apply time-lagged independent component analysis (tICA), an unsupervised dimensionality reduction algorithm, to molecular dynamics simulations with well-tempered metadynamics to find the slowest collective degrees of freedom of the permeation process of trimethoprim through a multicomponent membrane. We show that tICA-metadynamics yields translational and orientational collective variables (CVs) that increase convergence efficiency ∼1.5 times. However, crossing the periodic boundary is shown to introduce artefacts in the translational CV that can be corrected by taking absolute values of molecular features. Additionally, we find that the convergence of the tICA CVs is reached with approximately five membrane crossings, and that data reweighting is required to avoid deviations in the translational CV.
lncRNA-mRNA network analysis reveals novel biomarkers in prostate adenocarcinoma
Authors: Razavi Houri , Katanforoush Ali 
Published: August 2023

AbstractProstate adenocarcinoma (PRAD) is the second most frequent cancer among men worldwide. lncRNAs have been suggested as novel promising biomarkers for cancer diagnosis and prognosis and therapeutic targets. Despite the previous investigations, still, comprehensive studies are required to discover the regulatory roles of lncRNAs in PRAD.We introduced a PRAD lncRNA-mRNA network (PLMNET) to identify novel PRAD biomarkers and therapeutic targets among lncRNAs. The PLMNET is constructed based on RNAs that are differentially expressed and had strongly correlate with each other. PANTR1, HOXB-AS3, EMX2OS, GATA3-AS1, LINC01116, LINC02385 are PLMNET hubs that are considered key regulatory lncRNAs of PRAD. We also mapped PLMNET lncRNAs to their associated GO-terms and hallmarks. Literature review confirms our suggested biomarkers and their associated hallmarks.The high degree nodes of PLMNET, GATA3-AS1, EMX2OS, LINC01116, LINC02137, RP11-431N15.2, LINC01671, LINC02806, ENSG00000231196, ENSG00000244252, RP11-379F12.3, and SLC2A9-AS1 indicate significant association with overall survival. In addition, we found that the hubs’ regulatory roles have previously been confirmed in different types of cancers by literature. For example, PANTER hub exhibited a high expression correlation with three known tumor suppressors (SKI, SKP2, and SH2B3) and is associated with “Sustaining proliferative signal”. The literature has confirmed that PANTER may promote cancer cell proliferation in prostate carcinoma. It also promotes renal cell carcinoma and Hepatocellular carcinoma progression. Furthermore, literature review proves that EMX2OS and LINC01116 are key regulatory lncRNAs of prostate adenocarcinoma and HOXB-AS3 and GATA3-AS1 have regulatory roles in other cancer.According to pathway analysis, PLMNET hubs seem to contribute to PRAD proliferation, invasion, metastasis, and apoptosis via dysregulation of anaphase promoting complex/cyclosome (APC/C) subunits and dysregulation of mitotic cell cycle.These results introduce PLMCNET hubs as potential molecular biomarkers for diagnosis and prognosis of PRAD and suggest therapeutic targets for PRAD patients.
Structure of a benzosulfonamide based inhibitor – 11l - bound to a disulfide stabilised HIV-1 capsid hexamer
Authors: Barnett Michael , Sun Lin , Xu Shujing , Liu Xinyong , Zhan Peng , Goldstone David C. 
Published: August 2023

AbstractThe Human Immunodeficiency Virus Type 1 (HIV-1) continues to be a major global health issue, with infection leading to Acquired Immunodeficiency Syndrome (AIDS). Despite advances in antiviral therapy, the need for new and more effective treatments remains critical. In this study, we determined the structure of the disulfide stabilised HIV-1 capsid protein hexamer in complex with the novel antiviral capsid inhibitor compound 11l. The structure revealed the presence of six 11l molecules bound to the capsid hexamer in a conserved site shared by nuclear import factors, and other capsid inhibitor compounds such as PF74 and GS-6207. The 11l compound exhibits disorder in the benzo-sulfonamide groups and disruption in the loop between helix 8 and 9 for the capsid C-terminal domain, an important 2-fold symmetry axis for hexamer formation. Our findings provide insights into the mechanism of action of 11l as a capsid inhibitor and antiviral. These results contribute to the ongoing efforts to develop more effective antiviral treatments for the global burden of HIV and AIDS.SynopsisInsight into the mechanism of action for a novel HIV-1 capsid inhibitor antivirals are elucidated by structure of HIV-1 capsid hexamer bound to the novel inhibitor compound 11l.
Nucleoporin Elys attaches peripheral chromatin to the nuclear pores in interphase nuclei
Authors: Doronin Semen A. , Ilyin Artem A. , Kononkova Anna D. , Solovyev Mikhail A. , Olenkina Oxana M. , Nenasheva Valentina V. , Mikhaleva Elena A. , Lavrov Sergey A. , Ivannikova Anna Y. , Fedotova Anna A. , Khrameeva Ekaterina E. , Ulianov Sergey V. , Razin Sergey V. , Shevelyov Yuri Y. 
Published: August 2023

AbstractTransport of macromolecules through the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs) consisting of nucleoporins (Nups). Elys/Mel-28 is the Nup that binds and connects the decondensing chromatin with the reassembled NPCs at the end of mitosis. Whether Elys links chromatin with the NE during interphase is unknown. Using DamID-seq, we identified Elys binding sites inDrosophilalate embryos and divided them into those associated with nucleoplasmic or with NPC-linked Elys. These Elys binding sites are located within active or inactive chromatin, respectively. Strikingly,Elysknockdown in S2 cells results in peripheral chromatin displacement from the NE, in decondensation of NE-attached chromatin, and in derepression of genes within. It also leads to slightly more compact active chromatin regions. Our findings indicate that NPC-linked Elys, together with the nuclear lamina, anchors peripheral chromatin to the NE, whereas nucleoplasmic Elys decompacts active chromatin.Author summaryHeterochromatin in interphase nucleus is localized mostly at the nuclear periphery. However, the forces maintaining its peripheral localization are not well understood. Nuclear envelope consists of two lipid bilayer membranes separated by perinuclear space. The inner nuclear membrane is lined by the nuclear lamina, and both membranes are pierced by nuclear pore complexes composed of nucleoporins. Nuclear envelope can serve as a scaffold to which heterochromatin is attached. In the present study, we identified nucleoporin Elys as one of the key players maintaining peripheral localization of heterochromatin during interphase. Elys binds to multiple genomic sites located within heterochromatin and thus links it to nuclear pore complexes. However, the nucleoplasmic fraction of Elys binds to active genes and enhancers, resulting in decompactization of their chromatin.
Comparison of transthoracic ultrasonography, computer-assisted lung auscultation, and transtracheal wash cytology in stocker cattle with bovine respiratory disease
Authors: Scott Matthew A. , Woolums Amelia R. , Carter Hannah F. , Wills Robert W. , Bulla Camilo , Karisch Brandi B. 
Published: August 2023

AbstractField methods to diagnose bovine respiratory disease (BRD) do not accurately identify airway inflammation and lack clinical sensitivity. New diagnostic modalities, such as thoracic ultrasound (TU), computer-assisted lung auscultation (CALA), and transtracheal wash (TTW), have recently emerged which may deliver accurate diagnosis and prediction of BRD in clinical settings. Therefore, we sought to compare TU, CALA, and TTW fluid cytologic assessment in stocker cattle at risk for BRD in a pilot study. We enrolled 17 high-risk mixed-breed beef steers, sampled 10 and 21 days after arrival and conventional management, in a pilot cross-sectional observational study. Cattle were examined daily for 82 days for clinical BRD. On day 10, 16 cattle received CALA, and 10 and 8 of these received TU and TTW, respectively. On day 21, 12 cattle received CALA and TTW, and 10 received TU. CALA was scored as 1-5. Lung consolidation and/or comet tails were evaluated by TU. TTW was evaluated by 200-cell differential count, with inflammation defined as >20% neutrophils. Relationships between each diagnostic test, and between diagnostic tests and clinical BRD, were evaluated by logistic regression (P<0.10). Fourteen cattle were treated for BRD. CALA scores ranged 1-3; three cattle had lung consolidation. On day 10, 5 of 6 cattle previously treated for BRD and 0 of 3 not treated had >20% TTW neutrophils. On day 21, 5 of 9 treated cattle and 1 of 3 not treated had >20% TTW neutrophils. No significant relationship between CALA, TU, and TTW inflammation existed. TTW inflammation was associated with BRD diagnosis (P=0.0586). CALA and TU results were unrelated to TTW inflammation. Cytologic assessment of TTW may improve antemortem diagnosis of BRD.
Unique episymbiotic relationship betweenGracilibacteriaandZoogloeain activated sludge flocs in a municipal wastewater treatment plant
Authors: Fujii Naoki , Kuroda Kyohei , Narihiro Takashi , Aoi Yoshiteru , Ozaki Noriatsu , Ohashi Akiyoshi , Kindaichi Tomonori 
Published: August 2023

AbstractAmong the various bacteria present in activated sludge, uncultivatedPatescibacteria(also known as the Candidate Phyla Radiation/CPR superphylum) are ubiquitous at the class or phylum level.Patescibacteriahave a highly restricted metabolic capacity and are thought to be episymbiotic/endosymbiotic or predatory. However, only a limited number ofPatescibacteriaand their hosts have been identified. Therefore, manyPatescibacteriahave not been (co-)cultured and identified by fluorescencein situhybridization (FISH) or electron microscopy. Little is known about the morphology, metabolic potential, and hosts ofGracilibacteria(formerly GN02 or BD1-5) which belong toPatescibacteria. In our previous study, we confirmed the presence ofGracilibacteriain activated sludge and successfully recovered its high-quality genome. In this study, we designed new probes to visualize members ofGracilibacteriain activated sludge and identified its host using FISH. The FISH observations revealed thatGracilibacteria, which formed loosely associated clusters, were located within dense clusters ofZoogloea, which were dominant in the activated sludge. The metagenome-assembled genomes (MAGs) ofZoogloeapossessed genes related to extracellular polymeric substance (EPS) biosynthesis, floc formation, and nutrient removal, including a polyhydroxyalkanoate (PHA) accumulation pathway. The MAGs ofGracilibacteriapossessed genes associated with type IV pili, competence protein EC (ComEC), and PHA degradation, which suggests that they have aZoogloea-dependent lifestyle in activated sludge flocs. These findings clearly indicate a new symbiotic relationship betweenGracilibacteriaandZoogloea, and to the best of our knowledge, this is the first study to show this interaction.