bluuebunny/crossref_metadata_2025_split huggingface dataset:
A whole-plant perspective of hydraulic strategy in temperate desert shrub species
Authors: Tan Fengsen , Li Xu , Cao Wenxu , Zhu Shidan , Duan Na , Li Qinghe 
Published: October 2024

Abstract
Desert shrubs play a crucial role in controlling desertification and promoting revegetation, but drought often hinders their growth. Investigating the hydraulic strategies of desert shrubs is important in order to understand their drought adaptation and predict future dynamics under climate change. In this study, we measured the hydraulic-related characteristics of roots, stems and leaves in 19 desert shrub species from northern China. We aimed to explore the hydraulic coordination and segmentation between different plant organs. The results were as follows: (i) specific root length was positively correlated with the water potential inducing a 50% loss in stem hydraulic conductivity (P50stem) and negatively correlated with stem hydraulic safety margin. This suggested that water uptake efficiency of the fine roots was traded off with stem embolism resistance and hydraulic safety. (ii) The water potential inducing a 50% loss in leaf hydraulic conductance was significantly less negative than P50stem, and fine root turgor loss point was significantly less negative than P50stem, indicating a hydraulic segmentation between the main stem and terminal organs. (iii) The most negative leaf turgor loss point indicated that leaf wilting occurred after substantial leaf and stem embolism. The high desiccation resistance of the leaves may serve as an important physiological mechanism to increase carbon gain in a relatively brief growth period. In summary, this study elucidated the hydraulic strategies employed by desert shrubs from a whole-plant perspective.
Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2− advanced breast cancer: Final results of the randomized phase III MONARCH plus trial
Authors: Hu Xichun , Zhang Qingyuan , Sun Tao , Yin Yongmei , Li Huiping , Yan Min , Tong Zhongsheng , Li Man , Teng Yue’e , Oppermann Christina Pimentel , Kanakasetty Govind Babu , Portugal MA Coccia , Yang Liu , Zhang Wanli , Jiang Zefei 
Published: October 2024

Abstract

Background:
In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2− advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis.

Methods:
In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2− ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL).

Results:
In cohort A (abemaciclib: n = 207; placebo: n = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs. placebo (28.27 months vs. 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348–0.649). In cohort B (abemaciclib: n = 104; placebo: n = 53), abemaciclib plus fulvestrant improved median PFS vs. placebo (11.41 months vs. 5.59 months, HR: 0.480; 95% CI: 0.322–0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553–1.443; cohort B: HR: 0.512, 95% CI: 0.281–0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs. placebo.

Conclusions:
Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life.

Trial registration:

ClinicalTrials.gov (NCT02763566).
Therapeutic Drug Monitoring of High-dose Sulbactam in Pediatric Patients: Preliminary Data From a Prospective Observational Pharmacokinetic Study
Authors: Charoenwong Kankamol , Wacharachaisurapol Noppadol , Sukkummee Warumphon , Sophonphan Jiratchaya , Suchartlikitwong Pintip , Chatsuwan Tanittha , Anugulruengkitt Suvaporn , Puthanakit Thanyawee 
Published: October 2024

Background:
Rates of carbapenem-resistant Acinetobacter baumannii are rising in Thailand. Although high-dose (HD) sulbactam is recommended for treating carbapenem-resistant A. baumannii infections, data on plasma sulbactam concentrations in children are limited. We aimed to evaluate plasma sulbactam concentrations and pharmacokinetic-pharmacodynamic (PK-PD) target achievement in pediatric patients.

Methods:
Prospective study data (January–November 2023) on children (1 month–18 years) who received sulbactam every 6–8 hours were analyzed. Mid-dosing (C
mid, 50% fT) and trough (C
trough, 100% fT) concentrations were evaluated. PK-PD target achievement [50% fT > minimum inhibitory concentration (MIC), 100% fT > MIC] was evaluated using Clinical and Laboratory Standards Institute 2024 MIC cutoffs and MIC data of isolates of Acinetobacter calcoaceticus–baumannii complex from this study.

Results:
Thirty-five patients (median age 50 months) were categorized into standard-dose (SD) or HD groups. The geometric mean C
mid was higher in the HD (41.3 mg/L) versus SD (19.5 mg/L) groups (P = 0.006). Among 101 isolates of Acinetobacter calcoaceticus–baumannii complex, the MIC50 and MIC90 (concentrations that inhibit 50% and 90% of isolates of the A. calcoaceticus–baumannii complex) were 16 and 128 mg/L, respectively. The HD group achieved C
mid >MIC50 in 87.5% of the patients compared with 63.6% in SD (P = 0.17). Within the HD group, patients with augmented renal clearance (ARC) had lower C
mid (geometric mean 31.9 mg/L) compared with non-ARC (geometric mean 63.4 mg/L) (P = 0.04).

Conclusions:
HD sulbactam resulted in higher C
mid and PK-PD achievement. ARC significantly compromised plasma sulbactam concentration. HD sulbactam may be preferable for treating critically ill pediatric patients and those with ARC, especially during the empirical period.
Addressing Barriers to Implementing and Scaling PrEP in Carceral Settings: Applying Insights From Implementation Science
Authors: Rogers Brooke , Ramsey Susan , Ames Evan , Gomes Nyx , Murphy Matthew 
Published: October 2024

Introduction:
Within the United States, individuals experiencing incarceration are at higher risk for HIV acquisition than the general population, yet may face additional difficulty engaging in HIV prevention clinical services. HIV preexposure prophylaxis (PrEP) is an effective approach to preventing HIV transmission, and the Centers for Disease Control recommends that PrEP be offered in carceral settings, particularly during the vulnerable community reentry period. However, there have been few efforts to scale PrEP in this setting.

Methods:
Based on our experience implementing PrEP in Rhode Island's state carceral system, we have identified potential approaches to overcoming barriers to PrEP use in this unique practice environment by using the implementation research logic model. We then evaluated specific implementation determinants and barriers as well as strategies used to overcome those barriers to effectively scale PrEP in this setting.

Results:
We developed a “toolkit,” or 14-step guide, for others in the field to use for implementing PrEP in carceral settings, including the development and use of clinical protocols and community linkage strategies.

Discussion:
Our experiences with barriers in the carceral setting, identifying and leveraging implementation strategies, allowed us to develop a “toolkit” to guide other PrEP implementation projects in carceral settings. We encourage others to scale-out our work to other carceral settings to better reach and engage a group of individuals both at elevated risk for HIV and currently underserved by HIV prevention strategies, including PrEP.
Diagnostic Accuracy of 18F-FES PET/CT for the Detection of Recurrent and Metastatic Breast Cancer
Authors: Shin Eonwoo , Han Sangwon , Ryu Jeongryul , Eom Hye-Joung , Choi Woo Jung , Ahn Jin-Hee , Son Byung Ho , Ahn Seung Do , Gong Gyungyub , Moon Dae Hyuk 
Published: October 2024

Purpose
To evaluate the diagnostic value of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) PET/CT for distant metastasis or recurrence in patients with estrogen receptor (ER)–positive breast cancer.

Methods
Patients with ER-positive breast cancer and suspected of de novo metastasis or recurrence were retrospectively identified from a prospective cohort enrolled for a postmarketing surveillance study of 18F-FES at our institution. Per-patient diagnostic accuracy was assessed using pathology or 2 or more standard-of-care imaging procedures with a minimum of 6 months of follow-up as the reference standard. The per-region detection rate of 18F-FES PET/CT was evaluated and compared with that of standard-of-care imaging.

Results
Of the 162 included patients, 104 and 58 were suspected to have recurrence or de novo metastasis, respectively. The overall sensitivity and specificity of 18F-FES PET/CT were 95% (95% confidence interval [CI], 89%–98%) and 89% (95% CI, 76%–96%), respectively. When stratified according to clinical settings, the sensitivity and specificity were 95% (95% CI, 88%–99%) and 96% (95% CI, 78%–100%), respectively, for detecting recurrence, and 94% (95% CI, 81%–99%) and 82% (95% CI, 60%–95%) for detecting distant metastasis. In region-based analysis, the overall detection rate of 18F-FES PET/CT was significantly higher than that of standard-of-care imaging (92% [95% CI, 89%–94%] vs 83% [95% CI, 79%–87%], P < 0.001).

Conclusions

18F-FES PET/CT showed excellent diagnostic performance in patients with ER-positive breast cancer suspected of de novo metastasis or recurrence.
Hypertrophic Olivary Degeneration
Authors: Ganapathy Chandrasekaran , Tripathi Madhavi , D’Cruz Deula , Lodha Rakesh , Kumar Atin , Pandey Saumya , Bal CS 
Published: October 2024

Abstract
We present a case of 12-year-old boy evaluated in view of refractory ascites in whom 18F-FDG PET/CT incidentally revealed hypermetabolism in the medulla that was proven to be hypertrophic olivary degeneration on MRI.
Finite Element Modeling of Electrical Activity in Human Uterine Tissue: Advances in Simulation Techniques
Authors: Zahran Saeed 
Published: October 2024

AbstractSimulating the electrical activity of the human uterus has become a crucial tool for understanding the underlying biophysical phenomena, such as uterine contractions during pregnancy. Finite element models (FEM) offer valuable insights into these dynamics by providing a scalable framework to explore the propagation of electrical signals at the cellular and tissue levels. This study presents a finite element-based bidomain model to simulate the excitation propagation across the human uterus. Our model integrates cellular-level electrophysiological properties with tissue-level electrical propagation using the FEniCS Python library. A three-dimensional, realistic representation of uterine tissue is employed to simulate excitation patterns, contributing to a deeper understanding of uterine electrophysiology. The model can also be adapted to investigate pathological conditions such as preterm labor and test potential interventions. The developed simulation framework provides a scalable solution for the numerical challenges posed by solving complex, non-linear ordinary differential equations (ODEs) associated with uterine electrical activity. These simulations could offer a foundation for future research on uterine function and its related disorders.
Bioinformatics Analysis Suggests That SE_1780 protein from Staphylococcus epidermidis may be a member of the Fph Family of Lipases
Authors: Qaddourah Maya , Jayasinghe Sajith 
Published: October 2024

AbstractThe Protein Databank entry for protein SE_1780 from Staphylococcus epidermidis lists the function as unknown. We leveraged the framework outlined in the Biochemistry Authentic Scientific Inquiry Laboratory and used bioinformatics tools to ascertain the function of the protein. Based on our analysis we posit that SE_1780 is a lipase of theα/βhydrolase family with a proposed active site catalytic triad composed of Ser144, Asp235, and His269. Further we identified the lipase FphD as having significant sequence identity to protein SE 1780, and suggest that the protein is a member of the Fph family of lipases from S. epidermidis.
Identifying barriers to care and child mortality in urban and rural areas: a mixed method study in Sierra Leone
Authors: Elston James W.T. , Danis Kostas , Gray Nell , West Kim , Lokuge Kamalini , Black Benjamin , Stringer Beverley , Jimmisa Augustine S. , Biankoe Aiah , Sanko Mohammed O. , Kazungu Donald S. , Sang Sibylle , Baker Holly , Caleo Grazia 
Published: October 2024

AbstractBackgroundReducing mortality of children <5 years in Sierra Leone is a priority. Despite an enabling policy environment, health indicators have remained poor. Evidence on barriers to care is limited.ObjectivesThis study describes barriers to care, health-seeking behaviour, and health outcomes of children <5 years.MethodsFrom October 2016 to January 2017, we conducted a sequential mixed-methods study in urban and rural areas of Tonkolili District comprising: household survey targeting carers of children <5 years; and in-depth interviews (IDIs) targeting community leaders and healthcare workers (HCWs). We chose 30 clusters in urban and 30 clusters in rural areas. Topics that were identified during the survey were examined further through IDIs.ResultsWe surveyed 643 carers of 1092 children <5 years and conducted 72 IDIs. Of children <5 years, 62% had experienced febrile illness in the 2 weeks prior, and mortality was higher rurally (1.55/10,000/day vs urban 0.26/10,000/day). Barriers, including costs and physical inaccessibility of healthcare facilities, delayed or prevented 90% (287/318; 95%CI: 80-96) rural and 48% (155/325; 95%CI: 37-58) urban carers from accessing care for a febrile child. Mistrust of HCWs was frequent, primarily due to their requests for payment. HCWs described lack of pay and holistic support precluding provision of quality care.ConclusionsChildren <5 faced important barriers to healthcare, particularly in rural areas, contributing to high preventable mortality near to the emergency threshold. Access to healthcare was important to carers, however available services were costly and unreachable. Equally, HCWs experienced structural barriers to provide quality care.Key messagesChild <5years mortality near to the humanitarian emergency threshold and substantially high among rural children.Inequity in healthcare access and inequality in health between urban and rural areas.Barriers, including costs of healthcare and physical inaccessibility of healthcare facilities, delayed or prevented 90% of rural and 48% of urban carers from accessing care for a febrile child.Just 8% of rural children <5 years used Long-Lasting Insecticide-Treated bednets.Mistrust of healthcare workers was widely expressed primarily due to payment demanded for “free” healthcare. Healthcare workers described lack of pay and poor conditions precluding provision of quality care.
Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5’UTRs
Authors: Meguerditchian Caroline , Baux David , Ludwig Thomas E , Genin Emmanuelle , Trégouët David-Alexandre , Soukarieh Omar 
Published: October 2024

AbstractNon-canonical small Open Reading Frames (sORFs) are among main regulators of gene expression. The most studied ones are upstream ORFs (upORFs) located in the 5’UTR of coding genes. Internal ORFs (intORFs) in the coding sequence and downstream ORFs (dORFs) in the 3’UTR have received less attention. Different bioinformatics tools permit to predict single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool predict variants altering non-canonical translation initiation sites and those altering intORFs or dORFs.We propose an upgrade of our MORFEE bioinformatics tool to identify SNVs that may alter all types of sORFs in coding transcripts from a VCF file. Moreover, we generate an exhaustive catalog, named MORFEEdb, reporting all possible SNVs altering existing upORFs or creating new ones in human transcripts and provide an R script for visualizing the results. MORFEEdb has been implemented in the public platform Mobidetails. Finally, the annotation of ClinVar variants with MORFEE reveals that more than 45% of UTR-SNVs can alter upORFs or dORFs.In conclusion, MORFEE and MORFEEdb have the potential to improve the molecular diagnosis of rare human diseases and to facilitate the identification of functional variants from genome-wide association studies of complex traits.
Engineering liposomes with cell membrane proteins to disrupt melanosome transfer
Authors: Liu Chunhuan , Liu Yuchun , Xue Changhu , Yang Cheng , Weitz David A. , Jahnke Kevin 
Published: October 2024

AbstractCells communicate by transporting vesicles and organelles, essential for maintaining cellular homeostasis. However, excessive vesicle transfer can cause several diseases and medical conditions like hyperpigmentation due to an unregulated intercellular transfer of melanosomes. Current treatments often focus on eliminating the compartment contents with drugs but can cause significant side effects. Here, we engineer liposomes with cell membrane proteins to directly disrupt intercellular transport without specialized therapeutics. We demonstrate this approach by reducing melanosome transfer from melanocytes to keratinocytes. To achieve this, we incorporate keratinocyte cell membrane proteins into liposomes using microfluidics, which can enhance uptake by melanocytes while reducing uptake by keratinocytes. We also show that these engineered liposomes reduce melanosome transfer because they attach to the surface of pigment globules, impeding pigment globule uptake by keratinocytes. Our findings provide an effective strategy for reducing melanosome transfer to treat hyperpigmentation and introduce a drug-free approach for regulating cellular communication via extracellular vesicles and organelles.
Schizandrin A suppressed pancreatic cancer proliferation and cancer associated fibroblast activation via inhibiting the COX-2/ALOX5 shunting
Authors: Zeng Zhirui , Lei Shan , Wang Jingya , Li Dahuan , Yang Yushi , Tian Qianting , Hao Xiaojiang , Chen Tengxiang 
Published: October 2024

AbstractBackgroundSchizandrin A is major components extracted fromSchisandra chinenzis-Turcz. BaillandSchisandra sphenanthear Rend. etWils. Schizandrin A exhibits remarkable hepatoprotective, antiviral and anti-inflammatory effects. However, the anti-tumor effects and its molecular mechanism were still known limited.MethodsThe affinity between Schizandrin A and COX-2/ALOX5 protein was analyzed using network pharmacology, computer molecular docking, and surface plasmon resonance experiments. Bioinformatic analysis and review of clinical characteristics were conducted to assess the necessity of simultaneous blocking of COX-2 and ALOX5 in pancreatic cancer (PC). LC/MS metabolomics and RNA-sequencing were utilized to investigate the effects of schizandrin A on the activation and expression of COX-2/ALOX5 in PC cells. Biological function experiments were conducted to investigate the inhibitory effects of Schizandrin A on PC cell proliferation and cancer-associated fibroblast activationin vitroandin vivo.ResultsSchizandrin A demonstrated a high affinity for binding directly with COX-2 and ALOX5, with kinetic association constants of 14.8 μM and 21.8 μM, respectively. PC exhibited a significant COX-2/ALOX5 signature, while PC cases with a high COX-2/ALOX5 signature showed lower overall survival and disease-free survival rates. Treatment of PC cells with schizandrin A resulted in decreased COX-2/ALOX5 activity and expression, leading to inhibition of leukotriene and prostaglandin production, as well as suppression of the downstream pathway NF-kappaB signaling. Schizandrin A demonstrated significant inhibitory effects on the proliferation and sphericity of PC cellsin vitro, as well as on cell proliferationin vivo, while exhibiting low toxicity to normal tissues. Treatment of conditioned medium from PC cells with schizandrin A resulted in reduced induction of normal fibroblasts into cancer-associated fibroblasts. Furthermore, mutations in the binding sites of ALXO5 (Arg246) and COX-2 proteins (Ile124 and Ser126) resulted in a significant decrease in affinity to Schizandrin A, and blocking the inhibitory effects of schizandrin A.ConclusionsTaken together, schizandrin A directly bound with COX-2 and ALOX5, reduced their activation and leukotrienes and prostaglandins production, thus exhibiting distinguished effects on suppressing PC proliferation and inhibiting the ability of PC cell to induce normal fibroblasts to transform into tumor-associated fibroblasts. Therefore, schizandrin A represents a potentially novel therapeutic approach for PC.
Deep-sea fish reveal alternative pathway for vertebrate visual development
Authors: Fogg Lily G. , Isari Stamatina , Barnes Jonathan E. , Patel Jagdish Suresh , Marshall N. Justin , Salzburger Walter , Cortesi Fabio , de Busserolles Fanny 
Published: October 2024

AbstractVertebrate vision is accomplished by two phenotypically distinct types of photoreceptors in the retina: the saturation-resistant cones for the detection of bright light and the highly sensitive rods for dim light conditions [1]. The current dogma is that, during development, all vertebrates initially feature a cone-dominated retina, and rods are added later [2, 3]. By studying the ontogeny of vision in three species of deep-sea fishes, we show that their larvae express cone-specific genes in photoreceptors with rod-like morphologies. Through development, these fishes either retain this rod-like cone retina (Maurolicus mucronatus) or switch to a retina with true rod photoreceptors with expression of rod-specific genes and transcription factors (Vinciguerria mabahissandBenthosema pterotum). In contrast to the larvae of most marine fishes, which inhabit the bright upper layer of the open ocean, the larvae of deep-sea fishes occur deeper, exposing them to a dimmer light environment [4–7]. Spectral maxima predictions from molecular dynamics simulations and environmental light estimations suggest that using transmuted photoreceptors that combine the characteristics of both cones and rods maximises visual performance in these dimmer light conditions. Our findings provide molecular, morphological, and functional evidence for the evolution of an alternative developmental pathway for vertebrate vision.