bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Carriage of Streptococcus pneumoniae Is Associated With Increased Experimental Pneumococcal Carriage but Reduced Conjugate Vaccine Efficacy in a Human Challenge Model
Authors: Galafa Bridgette , Chikaonda Tarsizio , Kudowa Evaristar , Sichone Simon , Sibale Lusako , Thole Faith , Mkandawire Christopher , Dula Dingase , Nsomba Edna , Tembo Godwin , Chaponda Mphatso , Chirwa Anthony E , Nkhoma Vitumbiko , Ngoliwa Clara , Kamng'ona Raphael , Toto Neema , Makhaza Lumbani , Muyaya Alfred , Howard Ashleigh , Nyazika Tinashe K , Ndaferankhande John , Chimgoneko Lorensio , Banda Ndaziona P K , Chiwala Gift , Rylance Jamie , Ferreira Daniela , Jambo Kondwani C , Morton Ben , Henrion Marc Y R , Gordon Stephen B 
Published: July 2024

Abstract

Background
In Malawi, the national 13-valent pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than in the United States, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy.

Methods
Healthy adults aged 18 to 40 years were randomly assigned to PCV13 (n = 98) or saline (n = 106), followed by intranasal SPN 6B inoculation at 20 000 (n = 40), 80 000 (n = 74), or 160 000 (n = 90) colony-forming units/100 µL at 28 days postvaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 postinoculation using culture and multiplex quantitative polymerase chain reaction (qPCR) targeting the lytA/cpsA genes, and we compared carriage rates by vaccination status.

Results
Of 204 participants, 19.6% (n = 40) exhibited experimental carriage detected by culture and 25.5% (n = 52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n = 10/98) than the placebo group (28.3%, 30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13, 8%, 6/75; placebo, 25.9%, 21/81) vs those with natural carriage (PCV13, 14.8%, 4/27; placebo, 26.5%, 9/34). According to a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had lower VE (52%) vs participants with no natural carriage (69%).

Conclusions
We have shown that the PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers when compared with those without natural carriage at the inoculation visit.
Reducing diagnostic delays in acute hepatic porphyria using health records data and machine learning
Authors: Bhasuran Balu , Schmolly Katharina , Kapoor Yuvraaj , Jayakumar Nanditha Lakshmi , Doan Raymond , Amin Jigar , Meninger Stephen , Cheng Nathan , Deering Robert , Anderson Karl , Beaven Simon W , Wang Bruce , Rudrapatna Vivek A 
Published: July 2024

Abstract

Background
Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of 15 years on average. The advent of electronic health records (EHR) data and machine learning (ML) may improve the timely recognition of rare diseases like AHP. However, prediction models can be difficult to train given the limited case numbers, unstructured EHR data, and selection biases intrinsic to healthcare delivery. We sought to train and characterize models for identifying patients with AHP.

Methods
This diagnostic study used structured and notes-based EHR data from 2 centers at the University of California, UCSF (2012-2022) and UCLA (2019-2022). The data were split into 2 cohorts (referral and diagnosis) and used to develop models that predict (1) who will be referred for testing of acute porphyria, among those who presented with abdominal pain (a cardinal symptom of AHP), and (2) who will test positive, among those referred. The referral cohort consisted of 747 patients referred for testing and 99 849 contemporaneous patients who were not. The diagnosis cohort consisted of 72 confirmed AHP cases and 347 patients who tested negative. The case cohort was 81% female and 6-75 years old at the time of diagnosis. Candidate models used a range of architectures. Feature selection was semi-automated and incorporated publicly available data from knowledge graphs. Our primary outcome was the F-score on an outcome-stratified test set.

Results
The best center-specific referral models achieved an F-score of 86%-91%. The best diagnosis model achieved an F-score of 92%. To further test our model, we contacted 372 current patients who lack an AHP diagnosis but were predicted by our models as potentially having it (≥10% probability of referral, ≥50% of testing positive). However, we were only able to recruit 10 of these patients for biochemical testing, all of whom were negative. Nonetheless, post hoc evaluations suggested that these models could identify 71% of cases earlier than their diagnosis date, saving 1.2 years.

Conclusions
ML can reduce diagnostic delays in AHP and other rare diseases. Robust recruitment strategies and multicenter coordination will be needed to validate these models before they can be deployed.
Testing the evolutionary potential of an alpine plant: phenotypic plasticity in response to growth temperature outweighs parental environmental effects and other genetic causes of variation
Authors: Arnold Pieter A , Wang Shuo , Notarnicola Rocco F , Nicotra Adrienne B , Kruuk Loeske E B 
Published: July 2024

Abstract
Phenotypic plasticity and rapid evolution are fundamental processes by which organisms can maintain their function and fitness in the face of environmental changes. Here we quantified the plasticity and evolutionary potential of an alpine herb Wahlenbergia ceracea. Utilizing its mixed-mating system, we generated outcrossed and self-pollinated families that were grown in either cool or warm environments, and that had parents that had also been grown in either cool or warm environments. We then analysed the contribution of environmental and genetic factors to variation in a range of phenotypic traits including phenology, leaf mass per area, photosynthetic function, thermal tolerance, and reproductive fitness. The strongest effect was that of current growth temperature, indicating strong phenotypic plasticity. All traits except thermal tolerance were plastic, whereby warm-grown plants flowered earlier, grew larger, and produced more reproductive stems compared with cool-grown plants. Flowering onset and biomass were heritable and under selection, with early flowering and larger plants having higher relative fitness. There was little evidence for transgenerational plasticity, maternal effects, or genotype×environment interactions. Inbreeding delayed flowering and reduced reproductive fitness and biomass. Overall, we found that W. ceracea has the capacity to respond rapidly to climate warming via plasticity, and the potential for evolutionary change.
Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study)
Authors: Márquez-Rodas Iván , Álvarez Ana , Arance Ana , Valduvieco Izaskun , Berciano-Guerrero Miguel-Ángel , Delgado Raquel , Soria Ainara , Lopez Campos Fernándo , Sánchez Pedro , Romero Jose Luis , Martin-Liberal Juan , Lucas Anna , Díaz-Beveridge Roberto , Conde-Moreno Antonio-José , Álamo de la Gala Maria del Carmen , García-Castaño Almudena , Prada Pedro José , González Cao María , Puertas Enrique , Vidal Joana , Foro Palmira , Aguado de la Rosa Carlos , Corona Juan Antonio , Cerezuela-Fuentes Pablo , López Paco , Luna Pablo , Aymar Neus , Puértolas Teresa , Sanagustín Pilar , Berrocal Alfonso 
Published: July 2024

Abstract

Background
Encorafenib plus binimetinib (EB) is a standard-of-care treatment for advanced BRAFV600-mutant melanoma. We assessed the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response.

Methods
E-BRAIN/GEM1802 was a prospective, multicenter, single-arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved a partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression. Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%.

Results
The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After 2 months, icRR was 70.8% (95% CI: 55.9–83.1); 10.4% complete response. Median intracranial progression-free survival (PFS) and OS were 8.5 (95% CI: 6.4–11.8) and 15.9 (95% CI: 10.7–21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grades 3–4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%).

Conclusions
Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high-grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.
Corilagin functionalized decellularized extracellular matrix as artificial blood vessels with improved endothelialization and anti-inflammation by reactive oxygen species scavenging
Authors: Wang Xu , Fu Hanmei , Wu Huibin , Peng Xiaohua , Peng Xu , Yu Xixun , Liu Hui , Wu Junmei , Luo Ling , Yan Shan , Cheng Xinglin , Zhou Xiong , Yuan Xiangyang 
Published: July 2024

Abstract
The performance of biological-originated blood vessels in clinical remains disappointing due to fast occlusion caused by acute thrombosis or long-standing inflammation. How to prevent rapid degradation and inhibit acute inflammation but maintain their high bioactivity is still a significant challenge. As a bioactive polyphenol in various traditional Chinese medicine, Corilagin (Cor) exhibits excellent anticoagulant, anti-inflammatory and rapid ROS consumption properties. Inspired by abundant supramolecular interactions in organisms, we selected it to crosslink tissues via purely H-bonds to simulate these natural interactions without introducing potential toxic aldehyde or carboxyl groups. Results show that 2 mg/ml was selected as the optimal Cor concentration to form a stable crosslinking network (FI &gt; 95%) and effectively delay their degradation. Cor modification not only enhances ECs adhesion and monolayer function via accelerating VEGF and TGF-β secretion but also promotes macrophage transformation from pro-inflammatory M1 phenotype to anti-inflammatory M2 ones. In vitro and ex-vivo studies implied that Cor-crosslinked samples exhibited low platelet accumulation and decreased thrombin generation. In vivo evaluation further confirmed that Cor-introducing could effectively consume ROS, thus exhibiting rapid endothelialization, suppressed inflammation and reduced mineral deposition. Overall, Cor crosslinking provided a bright future for blood vessels’ long-term patency and adapted to various blood-contacting surfaces.
Simulation study for design of long counter for standard neutron fields from 1 keV to 20 MeV at NMIJ/AIST
Authors: Matsumoto Tetsuro , Masuda Akihiko , Harano Hideki , Manabe Seiya 
Published: July 2024

Abstract
A De-Pangher-type long counter was designed for neutron measurements in standard neutron fields based on the results of simulations using the MCNP6 code at the National Metrology Institute of Japan, the National Institute of Advanced Industrial Science and Technology. The effects of six parameters in the design on the energy response of the long counter were investigated. The energy response was then quantitatively evaluated for eight design candidates selected from the investigation. The calculation results show that these candidates have a flatter energy response from 100 eV to 10 MeV compared to that of the current long counter. These candidates also reduce the difference between the average energy response from 10 eV to 1 MeV and that from 10 to 20 MeV.
Impact of cardiac rehabilitation on erectile dysfunction in cardiovascular patients: a systematic review and meta-analysis
Authors: Sadeghi Masoumeh , Askari Ali , Bostan Fatemeh , Heidari Afshin , Rafiee Hamed , Alavi Tabatabaei Ghazaal , Ghasemi Golsa , Roohafza Hamidreza 
Published: July 2024

Abstract

Background
Cardiovascular diseases (CVDs) and erectile dysfunction (ED) frequently co-occur, significantly affecting the quality of life of individuals.

Aim
To assess the impact of cardiac rehabilitation (CR) on ED in patients with CVD through a systematic review and meta-analysis.

Methods
This study analyzed randomized controlled trials and other studies comparing CR with usual care for adult males (≥18 years) with any cardiac disease. Literature searches were extensive, and the risk of bias was evaluated by the Cochrane Collaboration tool. Data from 6 studies involving 668 participants were included in the meta-analysis.

Outcomes
The primary outcome was the improvement in ED, as measured with the International Index of Erectile Function.

Results
A statistically significant improvement in erectile function was observed across 6 studies, with a Morris dppc2 effect size of 0.38 (95% CI, 0.17-0.59). Despite initial high heterogeneity (I2 = 95.7%), identification and correction for selective outcome reporting bias mitigated this issue.

Clinical Translation
CR has a modest but statistically significant impact on improving ED in patients with CVD, indicating its potential positive contribution to the quality of life of this group.

Strengths and Limitations
The study’s strengths include a comprehensive literature search and a rigorous methodological approach. Limitations involve high heterogeneity among studies and a low level of evidence due to small sample sizes and study quality; however, the source of heterogeneity was identified and mitigated following risk-of-bias assessment.

Conclusion
The results suggest that CR has a statistically significant but modest impact on improving ED in patients with CVD. Clinicians should consider the integration of CR into the clinical management of these individuals. This study underscores the potential for CR to contribute positively to the quality of life for patients with CVD by addressing associated ED (PROSPERO: CRD42022374625).
Feminizing Patriarchy: Christian Churches and Gender Inequality in Rural Africa
Authors: Agadjanian Victor 
Published: July 2024

AbstractIn dialogue with the cross-national scholarship on gender and religion, the study uses a unique combination of rich qualitative and quantitative data from a predominantly Christian rural sub-Saharan setting to examine how churches modify, yet also sustain and even reinforce, patriarchal norms. It shows how churches replace the traditional, extended family-based model of gender inequality with a pseudo-modern model of individualized conjugal dependency. Although men increasingly disengage from the religious space, the growing feminization of that space does not translate into a more gender-egalitarian narrative: the church nurtures women’s agency yet also channels it to rearrange and reassert their subservience. To acquire legitimacy, church women are pressured to act as collective articulators, promoters, and guarantors of neo-patriarchal values and orders, and in particular, as builders and saviors of matrimonial integrity and viability. These dynamics reflect and are an integral part of the broader gendered constraints and precarities of contemporary rural society.
Promotion of maturation of human pluripotent stem cell-derived cardiomyocytes via treatment with the peroxisome proliferator-activated receptor alpha agonist Fenofibrate
Authors: Lee Seul-Gi , Rhee Jooeon , Seok Jin , Kim Jin , Kim Min Woo , Song Gyeong-Eun , Park Shinhye , Jeong Kyu Sik , Lee Suemin , Lee Yun Hyeong , Jeong Youngin , Kim C-Yoon , Chung Hyung Min 
Published: July 2024

Abstract
As research on in vitro cardiotoxicity assessment and cardiac disease modeling becomes more important, the demand for human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is increasing. However, it has been reported that differentiated hPSC-CMs are in a physiologically immature state compared to in vivo adult CMs. Since immaturity of hPSC-CMs can lead to poor drug response and loss of acquired heart disease modeling, various approaches have been attempted to promote maturation of CMs. Here, we confirm that peroxisome proliferator-activated receptor alpha (PPARα), one of the representative mechanisms of CM metabolism and cardioprotective effect also affects maturation of CMs. To upregulate PPARα expression, we treated hPSC-CMs with fenofibrate (Feno), a PPARα agonist used in clinical hyperlipidemia treatment, and demonstrated that the structure, mitochondria-mediated metabolism, and electrophysiology-based functions of hPSC-CMs were all mature. Furthermore, as a result of multi electrode array (MEA)-based cardiotoxicity evaluation between control and Feno groups according to treatment with arrhythmia-inducing drugs, drug response was similar in a dose-dependent manner. However, main parameters such as field potential duration, beat period, and spike amplitude were different between the 2 groups. Overall, these results emphasize that applying matured hPSC-CMs to the field of preclinical cardiotoxicity evaluation, which has become an essential procedure for new drug development, is necessary.
Walnut oil: a promising nutraceutical in reducing oxidative stress and improving cholinergic activity in an in vitro Alzheimer’s disease model
Authors: Demirel Göksun , Sanajou Sonia , Yirün Anıl , Çakır Deniz Arca , Özyurt Aylin Balcı , Berkkan Aysel , Baydar Terken , Erkekoğlu Pınar 
Published: July 2024

Abstract
Improving the quality of life in elderly patients and finding new treatment options for neurological diseases such as Alzheimer’s has become one of the priorities in the scientific world. In recent years, the beneficial effects and therapeutic properties of natural foods on neurological health have become a very remarkable issue. Walnut oil (WO) is a promising nutraceutical, with many phytochemicals and polyunsaturated fatty acids and is thought to be promising in the treatment of many neurological diseases and cognitive deficits, such as Alzheimer’s disease (AD). Polyphenolic compounds found in WO enhance intraneuronal signaling and neurogenesis and improve the sequestration of insoluble toxic protein aggregates. The objective of this study was to investigate the potential protective and therapeutic effects of WO in a model of AD induced by retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). In order to achieve this, the experimental groups were formed as follows: Control group, WO group, Alzheimer’s disease (AD) group, AD + WO applied group (AD + WO). WO supplementation almost significantly reduced oxidative stress in the ad model, providing 2-fold protection against protein oxidation. Additionally, WO showed a significant reduction in tau protein levels (2-fold), increased acetylcholine (ACh) levels (12%), and decreased acetylcholine esterase (AChE) activity (~50%). Since it has been known for centuries that WO does show any adverse effects on human health and has neuroprotective properties, it may be used in the treatment of AD as an additional nutraceutical to drug treatments.
Tip-to-base conduit widening remains consistent across cambial age and climates in Fagus sylvatica L.
Authors: Rita Angelo , Pericolo Osvaldo , Tumajer Jan , Ripullone Francesco , Gentilesca Tiziana , Saracino Antonio , Borghetti Marco 
Published: July 2024

Abstract
Water transport, mechanical support and storage are the vital functions provided by the xylem. These functions are carried out by different cells, exhibiting significant anatomical variation not only within species but also within individual trees. In this study, we used a comprehensive dataset to investigate the consistency of predicted hydraulic vessel diameter widening values in relation to the distance from the tree apex, represented by the relationship Dh ∝ Lβ (where Dh is the hydraulic vessel diameter, L the distance from the stem apex and β the scaling exponent). Our analysis involved 10 Fagus sylvatica L. trees sampled at two distinct sites in the Italian Apennines. Our results strongly emphasize that vessel diameter follows a predictable pattern with the distance from the stem apex and β ~ 0.20 remains consistent across cambial age and climates. This finding supports the hypothesis that trees do not alter their axial configuration represented by scaling of vessel diameter to compensate for hydraulic limitations imposed by tree height during growth. The study further indicates that within-tree variability significantly contributes to the overall variance of the vessel diameter-stem length exponent. Understanding the factors that contribute to the intraindividual variability in the widening exponent is essential, particularly in relation to interspecific responses and adaptations to drought stress.
Infection of Alfalfa Cotyledons by an Incompatible but Not a Compatible Species of Colletotrichum Induces Formation of Paramural Bodies and Secretion of EVs
Authors: Ghosh Suchismita , Regmi Kamesh C. , Stein Barry , Chen Jun , O'Connell Richard J. , Innes Roger W. 
Published: July 2024

Hemibiotrophic fungi in the genus Colletotrichum employ a biotrophic phase to invade host epidermal cells followed by a necrotrophic phase to spread through neighboring mesophyll and epidermal cells. We used serial block face-scanning electron microscopy (SBF-SEM) to compare subcellular changes that occur in Medicago sativa (alfalfa) cotyledons during infection by Colletotrichum destructivum (compatible on M. sativa) and C. higginsianum (incompatible on M. sativa). Three-dimensional reconstruction of serial images revealed that alfalfa epidermal cells infected with C. destructivum undergo massive cytological changes during the first 60 h following inoculation to accommodate extensive intracellular hyphal growth. Conversely, inoculation with the incompatible species C. higginsianum resulted in no successful penetration events and frequent formation of papilla-like structures and cytoplasmic aggregates beneath attempted fungal penetration sites. Further analysis of the incompatible interaction using focused ion beam-scanning electron microscopy (FIB-SEM) revealed the formation of large multivesicular body-like structures that appeared spherical and were not visible in compatible interactions. These structures often fused with the host plasma membrane, giving rise to paramural bodies that appeared to be releasing extracellular vesicles (EVs). Isolation of EVs from the apoplastic space of alfalfa leaves at 60 h postinoculation showed significantly more vesicles secreted from alfalfa infected with incompatible fungus compared with compatible fungus, which in turn was more than produced by noninfected plants. Thus, the increased frequency of paramural bodies during incompatible interactions correlated with an increase in EV quantity in apoplastic wash fluids. Together, these results suggest that EVs and paramural bodies contribute to immunity during pathogen attack in alfalfa. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .