bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of PrEP continuation and coverage in the first year of use: a latent class analysis of a programmatic PrEP trial in Kenya
Authors: Mugwanya Kenneth K. , Palayew Adam , Schaafsma Torin , Irungu Elizabeth M. , Bukusi Elizabeth , Mugo Nelly , Morton Jennifer , Odoyo Josephine , Ngure Kenneth , Baeten Jared M. ,   for the Partners Scale‐Up Project
Published: July 2023

AbstractIntroductionEffective PrEP use is critical for impact, but data are limited on common patterns of continuation and coverage among persons using PrEP in real‐world settings.MethodsData are from the Partners Scale‐Up Project, a programmatic stepped‐wedge cluster‐randomized trial to integrate PrEP delivery in 25 Kenyan public health facilities conducted between February 2017 and December 2021. We evaluated PrEP continuation using visit attendance and pharmacy refill records, and computed medication possession ratio to define coverage during the first year of use. Latent class mixture models were used to identify and characterize membership to different PrEP continuation patterns. Multinomial logistic regression was used to examine the association between group trajectories and demographic and behaviour characteristics.ResultsOverall, 4898 persons initiated PrEP, 54% (2640) were female, mean age was 33 years (standard deviation 11) and 84% (4092) had partners living with HIV. PrEP continuation was 57%, 44%, and 34% at 1, 3, and 6 months, respectively. Four unique trajectories of PrEP coverage were identified: (1) one‐fourth (1154) exhibited consistent high coverage throughout the year with 93%, 94%, 96%, and 67% continuing PrEP at months 1, 3, 6, and 12, respectively; (2) 13% (682) showed high coverage trajectory throughout 6 months but coverage rapidly declined thereafter (94%, 93%, 63%, and 10% continued at months 1, 3, 6, and 12, respectively); (3) 18.9% (918) exhibited moderate coverage trajectory with 91% of clients refilling PrEP at month 1 but nearly all dropped‐off thereafter (37%, 5%, and 4% continued at months 3, 6, and 12, respectively); and (4) 43.8% (2144) exhibited immediate discontinuation trajectory, in which nearly all did not have any subsequent PrEP refill. Overall, being female, older age, having partners living with HIV or of unknown HIV status were statistically associated with better PrEP continuation trajectories compared to the immediate discontinuation trajectory (p<0.05 for all).ConclusionsIn this analysis of a real‐world PrEP implementation programme in Kenya, we found four distinct patterns of PrEP continuation, with one‐third of users exhibiting consistent high continuation throughout 12 months and two‐fifths with immediate discontinuation patterns. These data may help guide tailored interventions to support PrEP continuation in this setting.
Antibody‐dependent NK‐cell and neutralizing antibody responses against the Spike protein of Wuhan‐Hu‐1 and Omicron BA.1 SARS‐CoV‐2 variants in vaccinated experienced and vaccinated naïve individuals
Authors: Albert Eliseo , Fernández‐Soto Daniel , Giménez Estela , Casanovas José María , Zulaica Joao , Álvarez‐Rodríguez Beatriz , Rusu Luciana , Geller Ron , Reyburn Hugh T. , Navarro David 
Published: July 2023

AbstractAntibodies triggering Fc‐mediated NK cell activity may contribute to protection against disease caused by SARS‐CoV‐2 infection in humans. However, how these Fc‐mediated humoral responses compare between individuals displaying hybrid immunity (Vac‐ex) and those fully vaccinated with no history of SARS‐CoV‐2 infection (Vac‐n) and whether they correlate with neutralizing antibody (NtAb) responses remains largely undetermined. In this retrospective study serum samples from 50 individuals (median age, 44.5 years; range, 11–85; 25 males), 25 Vac‐ex and 25 Vac‐n were studied. A flow‐cytometry‐based antibody‐mediated NK‐cell activation assay was used to quantitate effector NK‐cells stimulated to express LAMP1 (lysosomal associated membrane protein 1), MIP1 (Macrophage inflammatory protein 1), and interferon‐γ (IFNγ); NK cells isolated from two donors (D1 and D2) were used. NtAb levels targeting the Spike protein of Wuhan‐Hu‐1 and Omicron BA.1 SARS‐CoV‐2 variants were quantitated using a SARS‐CoV‐2 S pseudotyped neutralization assay. Regardless of the SARS‐CoV‐2 variant S antigen used in the NK‐cell activation assay, the frequency of NK cells stimulated to express LAMP‐1, MIP1β, and IFNγ was higher in Vac‐ex compared with Vac‐n (p values ranging from 0.07 to 0.006) for D1; this was only seen for BA.1 when NK cells from D2 were employed. The frequency of functional NK cells activated by antibody binding to either Wuhan‐Hu‐1 or Omicron BA.1 S protein was not significantly different for both VAC‐ex and VAC‐n. In contrast, NtAb titers against BA.1 were around 10‐fold lower than that against Wuhan‐Hu‐1. Vac‐ex displayed higher NtAb titers against both (sub)variants than Vac‐n. NK‐cell responses correlated poorly with NtAb titers (ρ ≤ 0.30). The data demonstrate higher cross‐reactivity across variants of concern for antibodies triggering Fc‐mediated NK cell than for NtAb. Moreover, Vac‐Ex seemed to display more robust functional antibody responses as compared with Vac‐n.
Serum neutralization of SARS‐CoV‐2 Omicron BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5 in individuals receiving Evusheld
Authors: Zhao Qianqian , Wang Xin , Zhang Ze , Liu Xuefei , Wang Ping , Cao Jin , Liang Qiming , Qu Jieming , Zhou Min 
Published: July 2023

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant is undergoing continuous evolution and convergent mutation. These new subvariants are raising concerns that they may evade neutralizing monoclonal antibodies (mAbs). We investigated the serum neutralization efficacy of Evusheld (cilgavimab and tixagevimab) against SARS‐CoV‐2 Omicron BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1, and XBB.1.5. A total of 90 serum samples from healthy individuals were collected in Shanghai. Anti‐RBD antibodies were measured and symptoms of infection with COVID‐19 were compared among those individuals. The neutralizing activity of serum against Omicron variants was analyzed by pseudovirus neutralization assays in 22 samples. Evusheld retained neutralizing activity against BA.2, BA.2.75, and BA.5, albeit with somewhat reduced titers. However, the neutralizing activity of Evusheld against BA.2.76, BF.7, BQ.1.1, and XBB.1.5 significantly decreased, with XBB.1.5 showing the greatest escape activity among the subvariants. We also observed that Evusheld recipients displayed elevated antibody levels in their serum, which efficiently neutralized the original variant, and exhibited different characteristics of infection than those who did not receive Evusheld. The mAb has partial neutralization activity against Omicron sublineages. However, the increasing doses of mAb and a larger size of population should be further investigated.
Assessment of the potential value of plasma Torque Teno virus DNA load monitoring to predict cytomegalovirus DNAemia in patients with hematological malignancies treated with small molecule inhibitors: A proof‐of‐concept study
Authors: de la Asunción Carlos Solano , Giménez Estela , Hernández‐Boluda Juan Carlos , Terol María José , Albert Eliseo , López Javier , García‐Gutiérrez Valentín , Andreu Rafael , Malo María Dolores García , Fox María Laura , Remigia María José , Amat Paula , Solano Carlos , Navarro David 
Published: July 2023

AbstractIt is unknown whether Torque Teno virus (TTV) DNA load monitoring could anticipate the development of infectious events in hematological patients undergoing treatment with small molecular targeting agents. We characterized the kinetics of plasma TTV DNA in patients treated with ibrutinib or ruxolitinib and assessed whether TTV DNA load monitoring could predict the occurrence of Cytomegalovirus (CMV) DNAemia or the magnitude of CMV‐specific T‐cell responses. Multicenter, retrospective, observational study, recruiting 20 patients treated with ibrutinib and 21 with ruxolitinib. Plasma TTV and CMV DNA loads were quantified by real‐time PCR at baseline and days +15, +30, +45, +60, +75, +90, +120, +150, and +180 after treatment inception. Enumeration of CMV‐specific interferon‐γ (IFN‐γ)‐producing CD8+ and CD4+ T‐cells in whole blood was performed by flow cytometry. Median TTV DNA load in ibrutinib‐treated patients increased significantly (p = 0.025) from baseline (median: 5.76 log10 copies/mL) to day +120 (median: 7.83 log10 copies/mL). A moderate inverse correlation (Rho = −0.46; p < 0.001) was found between TTV DNA load and absolute lymphocyte count. In ruxolitinib‐treated patients, TTV DNA load quantified at baseline was not significantly different from that measured after treatment inception (p ≥ 0.12). TTV DNA load was not predictive of the subsequent occurrence of CMV DNAemia in either patient group. No correlation was observed between TTV DNA loads and CMV‐specific IFN‐γ‐producing CD8+ and CD4+ T‐cell counts in either patient group. The data did not support the hypothesis that TTV DNA load monitoring in hematological patients treated with ibrutinib or ruxolitinib could be useful to predict either the occurrence of CMV DNAemia or the level of CMV‐specific T‐cell reconstitution; nevertheless, due to the small sample size, further studies involving larger cohorts are warranted to elucidate this issue.
Torque teno virus viral load predicts SARS‐CoV‐2 vaccine response in kidney transplant recipients
Authors: Solis Morgane , Benotmane Ilies , Gallais Floriane , Caillard Sophie , Fafi‐Kremer Samira 
Published: July 2023

AbstractTransplant recipients display poor responses to SARS‐CoV‐2 mRNA vaccines. In this retrospective study, we investigate torque teno virus (TTV) viral load (VL), a ubiquitous virus reflecting global immune response levels, as a predictive factor of vaccine response in kidney transplant recipients (KTR). Four hundred and fifty‐nine KTR having received two SARS‐CoV‐2 mRNA vaccine doses were enrolled, and 241 of them subsequently received a third vaccine dose. Antireceptor‐binding domain (RBD) IgG response was assessed after each vaccine dose and TTV VL was measured in pre‐vaccine samples. Prevaccine TTV VL > 6.2 log10 copies (cp)/mL was independently associated with nonresponse to two doses (odds ratio (OR) = 6.17, 95% confidence interval (CI95) = 2.42–15.78) as well as to three doses (OR = 3.62, 95% CI95 = 1.55–8.49). In nonresponders to the second dose, high TTV VL in prevaccine samples or measured before the third dose were equally predictive of lower seroconversion rates and antibody titers. High TTV VL before and during SARS‐CoV‐2 vaccination schedules are predictive of poor vaccine response in KTR. This biomarker should be further evaluated regarding other vaccine responses.
Regional features of future warming using high‐resolution downscaled multimodel climate scenarios in mainland China
Authors: Zhang Lei , Xu Yinlong , Zhao Yuncheng , Meng Chunchun , Wang Changgui , Lin Yihua 
Published: July 2023

AbstractThe frequency and magnitude of global warming events varies greatly across different regions and countries. The climatic diversity for China and future warming features are projected across 12 climatic zones based on the ensemble of the five well‐performing high‐resolution downscaled climate models for each zone. There are warming patterns for the mean near‐surface air temperature (Tm), maximum near‐surface air temperature (Tmax), minimum near‐surface air temperature (Tmin) as well as heatwave and frost events. Under RCP4.5 and RCP8.5 scenarios, the three indices (i.e., Tm, Tmax and Tmin) countrywide are likely to increase at respective rates of 0.30–0.31 and 0.64–0.67°C·decade−1. The extent of frost event (FE) are projected to decrease at a rate of −1912 and −4442 day·km−2·decade−1 while the extent of heatwave event (HE) increase at a rate of 1116 and 3557 day·km−2·decade−1 under RCP4.5 and RCP8.5 scenarios, respectively. A higher increment in temperatures, a decreasing trend in diurnal temperature range (DTR), frost days and FE are highlighted in the western and northern zones, while these trends are opposite in southern zones. The warming is likely to get faster in the current colder zones (western and northern zones) while heatwave is more intense and severe in Jianghuai, Jianghan, the south Yangzi River, South China and Xinjiang. These potential changes indicate that adaption and mitigation strategies are necessary in response to future warming.
Reclaimed saline‐alkali paddy field may be a hotspot of methane and ammonia emissions
Authors: Wang Xinyi , Lyu Jiao , Zhu Hui , Shutes Brian , Xu Yingying , Zhang Fuman 
Published: July 2023

AbstractSalinization and alkalization are global environmental issues, and a growing area of saline‐alkali land has been developed as paddy fields. However, the information on the characteristics and driving mechanisms of greenhouse gas (i.e., methane (CH4), carbon dioxide (CO2) and nitrous oxide (N2O)) and ammonia (NH3) emissions from paddy fields with different saline‐alkali levels is limited. We conducted a 137‐day mesocosm experiment to investigate these issues using light (L), moderate (M), and heavy (H) saline‐alkali soils with a history of reclamation of 20, 4 and 2 years, respectively. The results demonstrated that both the cumulative CH4 and NH3 fluxes in H treatment were significantly (p < 0.05) higher than L. While, the increasing saline‐alkali levels reduced the cumulative CO2 and N2O fluxes, respectively. With the increasing saline‐alkali levels, the species richness and diversity of microbial communities decreased. High saline‐alkali level inhibited the growth of ammonia‐oxidizing archaea, resulting in less N2O produced by nitrification, thus reducing N2O emission. Cumulative CH4 flux and the mcrA gene copy numbers showed a significant (p < 0.05) negative correlation. The gene copy number in H treatment was lower than M and L, respectively. The highest global warming potential and greenhouse gas intensity were observed in H treatment. Overall, recently reclaimed saline‐alkali paddy field with an initial heavy saline‐alkali level may be a hotspot of farmland CH4 and NH3 emissions, highlighting the necessity of optimizing water and fertilizer management for controlling these gas emissions at the initial stage of developing saline‐alkali lands into paddy fields.
A study on source dependent batch to batch variations in silk fibroin films for potential applications in corneal tissue engineering
Authors: R. Dan Febin , S. H. Varsha , M. S. Anju , R. K. Athira , Kasoju Naresh 
Published: July 2023

AbstractThe demand‐to‐supply gap, rejection rates, and the chances of infection associated with organ/tissue transplantation prompted researchers to find alternative solutions such as tissue engineering. Here, healthy cells are cultured over a biomaterial framework supplemented with growth factors to create bioartificial tissues. As a scaffolding biomaterial, silk fibroin (SF), a biopolymer obtained from Bombyx mori silk cocoons, offers unique properties. However, natural polymers, including SF, were criticized for preconceived source‐dependent batch‐to‐batch variations. Therefore, this study aims to prepare B. mori SF‐based films and investigate source‐dependent variations, if any. For this purpose, we have sourced silk cocoons from three geographical locations in India and processed them into films with a solvent‐casting approach. As a whole, our results indicate that there were slight variations in the morphological features in the raw cocoon stage; however, once processed, there were no significant differences in their topological, physical, chemical, optical, mechanical, or degradable properties with respect to the source. Further, all the films were found to be noncytotoxic and cytocompatible with corneal cells in vitro. Therefore, the study indicates no source‐dependent variations in biopolymers and suggested that SF from any source can be processed into biomaterials for potential biomedical applications.
A hierarchical self‐attention‐guided deep learning framework to predict breast cancer response to chemotherapy using pre‑treatment tumor biopsies
Authors: Saednia Khadijeh , Tran William T. , Sadeghi‑Naini Ali 
Published: July 2023

AbstractBackgroundPathological complete response (pCR) to neoadjuvant chemotherapy (NAC) has demonstrated a strong correlation to improved survival in breast cancer (BC) patients. However, pCR rates to NAC are less than 30%, depending on the BC subtype. Early prediction of NAC response would facilitate therapeutic modifications for individual patients, potentially improving overall treatment outcomes and patient survival.PurposeThis study, for the first time, proposes a hierarchical self‐attention‐guided deep learning framework to predict NAC response in breast cancer patients using digital histopathological images of pre‐treatment biopsy specimens.MethodsDigitized hematoxylin and eosin‐stained slides of BC core needle biopsies were obtained from 207 patients treated with NAC, followed by surgery. The response to NAC for each patient was determined using the standard clinical and pathological criteria after surgery. The digital pathology images were processed through the proposed hierarchical framework consisting of patch‐level and tumor‐level processing modules followed by a patient‐level response prediction component. A combination of convolutional layers and transformer self‐attention blocks were utilized in the patch‐level processing architecture to generate optimized feature maps. The feature maps were analyzed through two vision transformer architectures adapted for the tumor‐level processing and the patient‐level response prediction components. The feature map sequences for these transformer architectures were defined based on the patch positions within the tumor beds and the bed positions within the biopsy slide, respectively. A five‐fold cross‐validation at the patient level was applied on the training set (144 patients with 9430 annotated tumor beds and 1,559,784 patches) to train the models and optimize the hyperparameters. An unseen independent test set (63 patients with 3574 annotated tumor beds and 173,637 patches) was used to evaluate the framework.ResultsThe obtained results on the test set showed an AUC of 0.89 and an F1‐score of 90% for predicting pCR to NAC a priori by the proposed hierarchical framework. Similar frameworks with the patch‐level, patch‐level + tumor‐level, and patch‐level + patient‐level processing components resulted in AUCs of 0.79, 0.81, and 0.84 and F1‐scores of 86%, 87%, and 89%, respectively.ConclusionsThe results demonstrate a high potential of the proposed hierarchical deep‐learning methodology for analyzing digital pathology images of pre‐treatment tumor biopsies to predict the pathological response of breast cancer to NAC.
A new MILP formulation for the flying sidekick traveling salesman problem
Authors: Boccia Maurizio , Mancuso Andrea , Masone Adriano , Sterle Claudio 
Published: July 2023

AbstractNowadays, truck‐and‐drone problems represent one of the most studied classes of vehicle routing problems. The Flying Sidekick Traveling Salesman Problem (FS‐TSP) is the first optimization problem defined in this class. Since its definition, several variants have been proposed differing for the side constraints related to the operating conditions and for the structure of the hybrid truck‐and‐drone delivery system. However, regardless the specific problem under investigation, determining the optimal solution of most of these routing problems is a very challenging task, due to the vehicle synchronization issue. On this basis, this work provides a new arc‐based integer linear programming formulation for the FS‐TSP. The solution of such formulation required the development of a branch‐and‐cut solution approach based on new families of valid inequalities and variable fixing strategies. We tested the proposed approach on different sets of benchmark instances. The experimentation shows that the proposed method is competitive or outperforms the state‐of‐the‐art approaches, providing either the optimal solution or improved bounds for several instances unsolved before.
A dysregulated bile acids pool is associated with metabolic syndrome and gut microbial dysbiosis in early adolescence
Authors: Mancera‐Hurtado Yesenia , Lopez‐Contreras Blanca E. , Flores‐Lopez Regina , Villamil‐Ramirez Hugo , del Rio‐Navarro Blanca E. , Canizales‐Quinteros Samuel , Moran‐Ramos Sofia 
Published: July 2023

AbstractObjectiveThe increased prevalence of childhood metabolic syndrome (MetS) is a public health issue. It has been shown that a dysregulated bile acid (BA) profile could be involved in the development of MetS, in which the gut microbiota could have a significant role in BA levels. This study aimed to evaluate differences in serum BA levels in children with and without MetS and whether these levels were associated with gut microbial composition.MethodsA total of 100 children aged 10 to 12 years were enrolled in this study, 42 children with MetS (cases) and 58 control participants. Serum BAs were measured by liquid chromatography‐tandem mass spectrometry and gut microbiota was determined by 16S ribosomal RNA gene sequencing.ResultsChildren with MetS showed higher levels of total, secondary, and 12α‐hydroxylated BAs, as well as deoxycholic acid, and these were associated with dyslipidemia and insulin resistance markers. Interestingly, total BAs were negatively correlated with gut bacterial diversity (Shannon index: rho = −0.218, p = 0.035), whereas total, 12α‐hydroxylated, and secondary BAs, as well as deoxycholic acid, showed negative correlations with genera known for their potential health effects, including Bifidobacterium, Akkermansia, and Faecalibacterium.ConclusionsThis study suggests that childhood MetS is associated with a dysregulated BA pool and that these alterations could influence the abundance of potentially beneficial bacteria, thus contributing to gut microbial dysbiosis.
Watson‐Crick Base Pairing ofN‐Methoxy‐1,3‐Oxazinane (MOANA) Nucleoside Analogues within Double‐Helical DNA
Authors: Afari Mark N. K. , Nurmi Kasper , Virta Pasi , Lönnberg Tuomas 
Published: July 2023

AbstractHairpin oligodeoxynucleotides incorporating a (2R,3S)‐4‐(methoxyamino)butane‐1,2,3‐triol residue in the middle of the double‐helical stem and opposite to either one of the canonical nucleobases or an abasic 2‐(hydroxymethyl)tetrahydrofuran‐3‐ol spacer were synthesized. Under mildly acidic conditions, aromatic aldehydes reacted reversibly with these oligonucleotides, converting the (2R,3S)‐4‐(methoxyamino)butane‐1,2,3‐triol unit into a 2‐aryl‐N‐methoxy‐1,3‐oxazinane nucleoside analogue. The equilibrium of this reaction was found to be dependent on both the aldehyde and the nucleobase opposite to the modified residue. 9‐Formyl‐9‐deazaadenine, combining a large stacking surface with an array of hydrogen bond donors and acceptors, showed the highest affinity as well as selectivity consistent with the rules of Watson‐Crick base pairing. 5‐Formyluracil or indole‐3‐carbaldehyde, lacking in either stacking or hydrogen bonding ability, were incorporated with a much lower affinity and selectivity.