bluuebunny/crossref_metadata_2025_split huggingface dataset:
U.S. patient preferences for long‐acting HIV treatment: a discrete choice experiment
Authors: Graham Susan M. , Barthold Douglas , Hauber Brett , Brah Aaron T. , Saldarriaga Enrique , Collier Ann C. , Ho Rodney J. Y. ,   the Emory PREFER Team, Marconi Vincent C. , Simoni Jane M. 
Published: July 2023

AbstractIntroductionRecent advances in long‐acting antiretroviral therapy (LA‐ART) could provide new options for HIV treatment and reduce adherence barriers, if regimens are acceptable to patients. We elicited preferences for key attributes of potential LA‐ART regimens among people with HIV (PWH) in the United States, focusing on four treatment modes (oral tablets, subcutaneous injections, intramuscular injections, and implants), product characteristics and location of administration.MethodsA discrete choice experiment was conducted among PWH aged ≥18 years recruited from HIV clinics in Washington State and Atlanta, Georgia from March 2021 to June 2022. Participants responded to 17 choice scenarios, each with three options: two systematically generated hypothetical LA‐ART regimens and a constant opt‐out (their current daily oral treatment). LA‐ART regimen descriptions included treatment mode, pain, dosing frequency, location, pre‐treatment time with undetectable viral load, pre‐treatment negative reaction testing and “late‐dose leeway” (i.e. flexibility or forgiveness in timing the next dose). We used conditional logistic regression, with an interaction between treatment mode and pain, to estimate preference weights for all attribute levels.ResultsSeven hundred participants (350 at each site) enrolled, with median age 51 years (range 18–73); 70% identified as cisgender male, 24% as cisgender female and 6% as non‐binary or transgender. LA oral tablets were the only mode preferred over current daily oral treatment, with annual implants and injections the next most preferred LA‐ART option. Longer time between doses was preferred, and administration at home was preferred to clinics, which were preferred to pharmacies. Attributes with less impact on preferences included oral lead‐in treatment to achieve viral suppression or test for negative reactions and late‐dose leeway around the prescribed dosing interval. Participants in Atlanta were more likely to prefer their current daily oral ART than participants from Seattle.ConclusionsPWH in the United States may soon have several options for LA‐ART. Our results suggest that LA oral tablets will be preferred by many patients over their current daily oral treatment, while implants and injections with longer duration may be acceptable to some. Future research should investigate sources of preference heterogeneity and actual uptake of and adherence to LA‐ART products, when available.
Preparing for long‐acting PrEP delivery: building on lessons from oral PrEP
Authors: Celum Connie , Grinsztejn Beatriz , Ngure Kenneth 
Published: July 2023

AbstractIntroductionWith recent approvals of long‐acting (LA) HIV pre‐exposure prophylaxis (PrEP) in the form of injectable cabotegravir and the dapivirine ring, programmes need to consider how to optimize the delivery of PrEP methods, including by leveraging lessons from the past decade of oral PrEP delivery.DiscussionFramed around differentiated service delivery building blocks, the major considerations for the delivery of LA PrEP are how to reach the populations who would most benefit from PrEP, where to locate PrEP services, how to reduce the user burden of accessing and continuing with PrEP, and how to integrate PrEP with other services. Demand creation for LA PrEP and education about new LA PrEP options should be co‐developed with communities and be positively framed. Client‐facing clinical decision support tools provide information about HIV prevention and PrEP options in non‐technical ways and can support their informed decision‐making about PrEP. Training for providers is needed to increase their ability to ask about sexual and drug use behaviours in a non‐judgmental and comfortable manner as part of risk assessment, discuss harm reduction strategies and counsel about available PrEP options that fit clients’ circumstances and needs. PrEP adherence support should include supportive counselling and be tailored to address an individual's particular barriers and needs. Reminders through text messaging or calls can foster PrEP persistence, given the narrow the window around dosing for injectable cabotegravir. Strategies are needed to expand PrEP delivery options, including telePrEP, pharmacy‐based PrEP, key population‐led services and mobile venues. Integrated delivery models are needed which include sexually transmitted infection testing and treatment, contraception for cis‐women not desiring to become pregnant, PrEP for pregnant women in high HIV prevalence settings, and gender‐affirming hormones and support for transgender persons.ConclusionsThe outcome of expanding PrEP options through LA PrEP formulations is to increase PrEP coverage, adherence, persistence and effectiveness by offering a choice of PrEP that meets the needs of persons who would benefit from PrEP. The lessons learned from the delivery of oral PrEP about demand creation, informed client decision‐making, provider training, adherence support and service delivery model are relevant to the delivery of LA PrEP and integration with other services.
Implementation and resource needs for long‐acting PrEP in low‐ and middle‐income countries: a scoping review
Authors: Castor Delivette , Heck Craig J. , Quigee Daniela , Telrandhe Niharika Vasant , Kui Kiran , Wu Jiaxin , Glickson Elizabeth , Yohannes Kibret , Rueda Sergio Torres , Bozzani Fiammetta , Meyers Kathrine , Zucker Jason , Deacon Justine , Kripke Katharine , Sobieszczyk Magdalena E. , Terris‐Prestholt Fern , Malati Christine , Obermeyer Chris , Dam Anita , Schwartz Katie , Forsythe Steven 
Published: July 2023

AbstractIntroductionSeveral low‐ and middle‐income countries (LMICs) are preparing to introduce long‐acting pre‐exposure prophylaxis (LAP). Amid multiple pre‐exposure prophylaxis (PrEP) options and constrained funding, decision‐makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP. We assessed how primary costing evidence aligned with those domains.MethodsWe conducted a rapid review of CIPs for oral PrEP and family planning (FP) to develop a consensus of implementation domains, and a scoping review across nine electronic databases for publications on PrEP costing in LMICs between January 2010 and June 2022. We extracted cost data and assessed alignment with the implementation domains and the Global Health Costing Consortium principles.ResultsWe identified 15 implementation domains from four national PrEP plans and FP‐CIP template; only six were in all sources. We included 66 full‐text manuscripts, 10 reported LAP, 13 (20%) were primary cost studies‐representing seven countries, and none of the 13 included LAP. The 13 primary cost studies included PrEP commodities (n = 12), human resources (n = 11), indirect costs (n = 11), other commodities (n = 10), demand creation (n = 9) and counselling (n = 9). Few studies costed integration into non‐HIV services (n = 5), above site costs (n = 3), supply chains and logistics (n = 3) or policy and planning (n = 2), and none included the costs of target setting, health information system adaptations or implementation research. Cost units and outcomes were variable (e.g. average per person‐year).DiscussionLAP planning will require updating HIV prevention policies, technical assistance for logistical and clinical support, expanding beyond HIV platforms, setting PrEP achievement targets overall and disaggregated by method, extensive supply chain and logistics planning and support, as well as updating health information systems to monitor multiple PrEP methods with different visit schedules. The 15 implementation domains were variable in reviewed studies. PrEP primary cost and budget data are necessary for new product introduction and should match implementation plans with financing.ConclusionsAs PrEP services expand to include LAP, decision‐makers need a framework, tools and a process to support countries in planning the systematic rollout and costing for LAP.
Effect of a multinutrient supplement as an adjunct to nonsurgical treatment of periodontitis: A randomized placebo‐controlled clinical trial
Authors: Laky Brenda , Bruckmann Corinna , Blumenschein Julian , Durstberger Gerlinde , Haririan Hady 
Published: July 2023

AbstractBackgroundThe aim of this double‐blind randomized placebo‐controlled clinical trial was to evaluate the efficacy of a multinutrient supplement as an add‐on therapy to scaling and root planing for patients with periodontitis.MethodsForty‐two patients with stage III or IV periodontitis were randomly allocated to a 2‐month treatment of either a multinutrient supplement containing vitamin C, vitamin E, zinc, selenium, alpha‐lipoic‐acid, cranberry extract, grapeseed extract, and coenzyme Q10 or placebo capsules as an adjunct to conservative periodontal therapy. Periodontal parameters, including probing pocket depth, gingival recession, bleeding on probing, approximal plaque index, and papillary bleeding index, were assessed. Clinical attachment loss, periodontal inflamed surface area, periodontal epithelial surface area, and percentages of pocket sites with ≤3, ≤4, ≥5, ≥6, ≥7, and ≥4 mm with bleeding on probing were calculated.ResultsAll clinical parameters significantly improved from baseline to reevaluation within each group (p < 0.05). Multinutrient intake resulted in a significantly higher reduction of probing‐pocket‐depth (−0.75 ± 0.42 mm) and bleeding‐on‐probing (−21.9 ± 16.1%) from baseline to reevaluation compared with placebo (−0.51 ± 0.30 mm, p = 0.040 and −12.5 ± 9.8%, p = 0.046, respectively). All periodontal parameters showed insignificantly higher improvements in patients receiving the supplement compared with those receiving the placebo (p > 0.05).ConclusionsMultinutrient supplementation as an adjunct to nonsurgical treatment of periodontitis showed some additional benefit regarding probing‐pocket‐depth and bleeding‐on‐probing. However, the clinical relevance needs to be further explored.
A comparison of soil liming requirement methodologies in temperate, Northern European pedo‐climates
Authors: Boyko Rose , Paton Graeme , Walker Robin , Watson Christine , Norton Gareth 
Published: July 2023

AbstractBackgroundLiming agricultural land is essential to optimise crop yield and soil nutrients. Despite the importance of pH management in agricultural soils, liming applications have been decreasing in the United Kingdom for decades. There is no comparison of contemporary and historical liming requirement (LR) methods for Northern European, temperate climate mineral soils high in organic matter (OM).AimsThe aims of this research were to thoroughly comparatively analyse current methodologies and to ascertain which soil characteristics contribute to LR reactions.MethodsAnalysis compared methods for determining liming values common in the United Kingdom (Scottish Agricultural College [SAC] look‐up chart, RothLime model), Europe and the United States (Shoemaker–McLean–Pratt, Sikora, Modified Mehlich buffers), and the 30‐min calcium hydroxide titration developed by the University of Georgia.ResultsRothLime and SAC highly underestimated the LR value in acidic soils. The buffers highly over or underestimated LRs. The UGA titration method is a cheap, easy and accurate method which could be utilised for high OM soils but requires further calculation development. The characteristics most associated with soil–lime reactions in this experiment were measures of exchangeability (cation exchange capacity and loss on ignition, and by proxy, lime buffering capacity).ConclusionsThere is an opportunity to create buffer calculators and titration equations adapted to high OM soils. These are suggested for further development, through a larger diversity of UK soil types grouped by buffering capacity ranges. Including soil exchangeability factors in lime management calculations may contribute to more accurate values and therefore better resource management. Increasing LR accuracy for site‐specific soil pH management, used in precision agriculture technologies, is a necessary tool for the conservation of natural resources like limestone, managing resource use efficiency, and for optimising yields.
Perceptions of pesticide use and health risks among apple growers in Kashmir Himalaya
Authors: Ashraf Moieza , Hassan Saima , Dar Shahid Ahmad 
Published: July 2023

AbstractBackgroundUnderstanding the patterns of pesticide use is important in protecting the environment and farmer's health for improvement of sustainability in chemical pest control. Studies on the knowledge and awareness of pesticides by farmers are often incomplete. Therefore, our study aimed at investigating the awareness and knowledge of pesticides from a detailed survey of 394 apple growers in the Kashmir Himalaya.ResultsThe study revealed that farmers have inadequate knowledge and awareness about pesticides. About 47.2% of the farmers are choosing pesticides based on the efficiency of the pest/pathogen control, 38.1% are choosing pesticides based on the cost of the product, and 14.7% of the farmers are choosing pesticides based on ease of availability. Most of the farmers rated the principles of Integrated Pest Management (IPM) as not important. The farmers believed that the use of pesticides is the only way of controlling the pest outbreaks that ultimately led to reckless spraying of pesticides. Our results revealed that farmers are spraying pesticides without protective gears and inappropriate dumping of pesticides and their containers, risking the health of humans and the environment. Almost 96% of the farmers feel burning and irritation to the eyes and skin, headache, and vomiting due to pesticide spraying. The results of this research work accentuate the requirement to educate apple growers about the adequate and safe use of pesticides to avoid risks to public and environmental health.ConclusionThe study concludes that farmers are significantly impacted by the use of pesticides. Ineffective actions of pesticide dealers, government regulations, and illiteracy of farmers are the main causes of the reckless use of pesticides. Therefore, special attention should be paid towards sustainable approaches of pesticide spraying and use of safety gears like personal protective equipment, for protection of human and environmental health.
Effects of soluble glucomannan and insoluble cellulose treatment on mucin secretion and mucin glycosylation‐related gene expression in the colons of mice
Authors: Zhang Fan , Zhao Yirun , Liu Xiang , Li Zhong , Liu Nian , Tang Lizi , Jiang Qian , Fan Zhiyong , Tan Bie , Li Yulian , Ma Xiaokang 
Published: July 2023

AbstractBackgroundFiber added to the diet can promote intestinal mucin secretion, relieve intestinal inflammation, and enhance the intestinal barrier function. Glycosylation is the key to mucin function. However, there are few studies on the correlation between dietary fiber and mucin glycosylation, especially two kinds of dietary fiber with different solubility. The aim of this study was to investigate the effects of soluble glucomannan (GM) and insoluble cellulose (CL) treatment on mucin secretion and mucin glycosylation‐related gene expression in the colons of mice.ResultsThe GM group significantly increased the goblet cell number, crypt depth, and the expression of mucin 2 (Muc2) and mucin 3a (Muc3a) genes in the colon. At the same time, the analysis of the colon transcriptome showed that the GM group changed the expression of genes related to the mucin glycosylation process, and the GM group up‐regulated the expression of Gcnt3, Gcnt4, St3gal1, Galnt13, and B3gnt6 genes involved in the O‐glycosylation process. Similarly, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that differentially glycosylated genes in the GM group were mainly related to the biosynthesis of mucin type O‐glycans, while the genes in the CL group were related to the biosynthesis of various types of N‐glycans. The correlation analysis between colonic microbes and differentially glycosylated genes also showed that the abundance of Alistipes in the GM group was significantly associated with the expression of Gcnt3, a key glycosylation gene.ConclusionGlucomannan treatment was more favorable for colonic Muc2 and Muc3a secretion and mucin O‐glycosylation gene expression. © 2023 Society of Chemical Industry.
Estimating the hydrophobicity extent of molecular fragments using reversed‐phase liquid chromatography
Authors: Carotti Andrea , Varfaj Ina , Pruscini Ilaria , Abualzulof Ghaid W. A. , Mercolini Laura , Bianconi Elisa , Macchiarulo Antonio , Camaioni Emidio , Sardella Roccaldo 
Published: July 2023

A fast HPLC method was developed to study the hydrophobicity extent of pharmaceutically relevant molecular fragments. By this strategy, the reduced amount of sample available for physico‐chemical evaluations in early‐phase drug discovery programs does not represent a limiting factor. The sixteen acid fragments investigated were previously synthesized also determining potentiometrically their experimental log D values. For four fragments it was not possible to determine such property since their values were outside of the instrumental working range (2 < pKa < 12). An RP‐HPLC method was therefore optimized. For each scrutinized method, some derived chromatographic indices were calculated, and Pearson's correlation coefficient (r) allowed to select the so‐called “φ0 index” as the best correlating with the log D. The was fixed at 3.5 and a modification of some variables [organic modifier (methanol vs. ACN), stationary phase (octyl vs. octadecyl), presence/absence of the additives n‐octanol, n‐butylamine, and n‐octylamine], allowed to select the best correlation conditions, producing a r = 0.94 (p < 0.001). Importantly, the φ0 index enabled the estimation of log D values for four fragments which were unattainable by potentiometric titration. Moreover, a series of molecular descriptors were calculated to identify the chemical characteristics of the fragments explaining the obtained φ0. The number of hydrogen bond donors and the index of cohesive interaction correlated with the experimental data.
Small particles and heterotrophic protists support the mesopelagic zooplankton food web in the subarctic northeast Pacific Ocean
Authors: Shea Connor H. , Wojtal Paul K. , Close Hilary G. , Maas Amy E. , Stamieszkin Karen , Cope Joseph S. , Steinberg Deborah K. , Wallsgrove Natalie , Popp Brian N. 
Published: July 2023

AbstractA quantitative understanding of the mesopelagic zooplankton food web is key to development of accurate carbon budgets and geochemical models in marine systems. Here we use compound specific nitrogen stable isotope analysis of amino acids to quantify the trophic structure of the microzooplankton and mesozooplankton community during summer in the subarctic northeast Pacific Ocean during the EXport Processes in the Ocean from Remote Sensing (EXPORTS) field campaign. Source amino acid values in particles and zooplankton provide strong evidence that basal resources for the mesopelagic zooplankton food web were primarily small (), suspended or slow‐sinking particles, but that surface organic matter delivered by vertically migrating zooplankton may have also been important. Comparisons of values of source and trophic amino acids provide estimates of food web length, which decrease significantly with depth and suggest that protistan microzooplankton are key components of the food web from the surface to at least 500. These results emphasize the importance of small particles as a source of carbon and nitrogen to mesopelagic communities in this region, support observations of an inverse relationship between zooplankton vertical migration and small particles as sources of carbon to deep‐sea food webs in low productivity environments, and document the role of heterotrophic protists as key trophic intermediaries in the mesopelagic zone at this location.
The response of a freshwater copepod to small‐scale, dissipative eddies in turbulence
Authors: Ruszczyk Melissa , Webster Donald R. , Yen Jeannette 
Published: July 2023

AbstractThe freshwater copepod Hesperodiaptomus shoshone was exposed to a Burgers vortex, a flow feature meant to mimic small‐scale, dissipative turbulent eddies found in the organism's environment, to determine how this copepod responds to microscale turbulent flow structures. Male and female H. shoshone were separately exposed to four turbulence intensity levels plus a negative control (i.e., stagnant flow) in two vortex orientations relative to gravity. H. shoshone demonstrates a mild behavioral change in the presence of a Burgers vortex that is dependent on both sex and vortex orientation. H. shoshone swim with fairly linear trajectories across all four levels of turbulence intensity, which is a notable difference from the swimming behavior of marine copepods exposed to the same flow feature. Variations in morphology, physical environment, or ecological niche between H. shoshone and marine copepods are potential factors that may explain the differences in how the species respond to a Burgers vortex. The setal array of H. shoshone differs from the setal array of the previously studied marine copepods, suggesting differences in sensory ability and response. The small pond habitat of H. shoshone is rarely or intermittently mixed, creating a different hydrodynamic landscape compared to the ocean, which may influence the copepod/turbulence interaction. H. shoshone has few, if any, naturally occurring predators whereas marine copepods have many, which may influence the difference in response to microscale turbulence.
Integrated multiomic analysis and high‐throughput screening reveal potential gene targets and synergetic drug combinations for osteosarcoma therapy
Authors: Zhang Wenchao , Qi Lin , Liu Zhongyue , He Shasha , Wang Cheng‐zhi , Wu Ying , Han Lianbin , Liu Zhenxin , Fu Zheng , Tu Chao , Li Zhihong 
Published: July 2023

AbstractAlthough great advances have been made over the past decades, therapeutics for osteosarcoma are quite limited. We performed long‐read RNA sequencing and tandem mass tag (TMT)‐based quantitative proteome on osteosarcoma and the adjacent normal tissues, next‐generation sequencing (NGS) on paired osteosarcoma samples before and after neoadjuvant chemotherapy (NACT), and high‐throughput drug combination screen on osteosarcoma cell lines. Single‐cell RNA sequencing data were analyzed to reveal the heterogeneity of potential therapeutic target genes. Additionally, we clarified the synergistic mechanisms of doxorubicin (DOX) and HDACs inhibitors for osteosarcoma treatment. Consequently, we identified 2535 osteosarcoma‐specific genes and several alternative splicing (AS) events with osteosarcoma specificity and/or patient heterogeneity. Hundreds of potential therapeutic targets were identified among them, which showed the core regulatory roles in osteosarcoma. We also identified 215 inhibitory drugs and 236 synergistic drug combinations for osteosarcoma treatment. More interestingly, the multiomic analysis pointed out the pivotal role of HDAC1 and TOP2A in osteosarcoma. HDAC inhibitors synergized with DOX to suppress osteosarcoma both in vitro and in vivo. Mechanistically, HDAC inhibitors synergized with DOX by downregulating SP1 to transcriptionally modulate TOP2A expression. This study provided a comprehensive view of molecular features, therapeutic targets, and synergistic drug combinations for osteosarcoma.