bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended stability of vasopressin 0.2 unit/mL in PVC containers
Authors: Bae Hyunbeom , Weaver Eric , Ellis Steffani , Murray Jason
Published: October 2022

Purpose

Vasopressin is used to maintain blood pressure in vasodilatory shock. Vasopressin is diluted from concentrated vials prior to administration as a continuous infusion. This study evaluates the physical and chemical stability changes of vasopressin diluted to 0.2 units/mL with 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags stored under refrigeration.

Methods

Vasopressin Injection, USP, 20 unit/mL solution was diluted to 0.2 unit/mL with 0.9% sodium chloride injection, and stability changes were evaluated over 10 days via mass spectrometry on days 0, 7, and 10.

Results

Solutions of vasopressin 0.2 unit/mL in 0.9% sodium chloride injection in PVC bags were physically stable and showed less than 10% degradation over 10 days of refrigerated storage.

Conclusion

Vasopressin 0.2 unit/mL may be given a beyond-use date (BUD) of 10 days based on United States Pharmacopeia BUD recommendations, with this study showing less than 10% degradation over 10 days of refrigerated storage.
Situationism and trait-eliciting situations
Authors: Piovarchy Adam
Published: October 2022

Doris, in his 2002 book Lack of Character and 2005 paper ‘Replies: evidence and sensibility’, famously argues that we lack the kinds of global character traits posited by theories of virtue, because the situationist experiments demonstrate that people do not display trait-relevant behaviour in trait-relevant situations above chance. This paper argues that some notable situationist experiments are not trait-relevant situations. By analysing which factors improve or reduce participants’ chances of success (e.g. stress, lack of familiarity, ambiguity), and observing that these factors decrease agents’ capacity to recognize and respond to a variety of reasons in a variety of settings, the best explanation of many subjects’ failure to do the right thing is that they are affected by factors that are capacity-compromising. This matters, because settings in which agents have a reduced capacity to avoid wrongdoing are typically not apt tests of an agent’s character traits.
Detecting signals of adaptive evolution in grape plastomes with a focus on the Cretaceous–Palaeogene (K/Pg) transition
Authors: Zecca Giovanni , Panzeri Davide , Grassi Fabrizio
Published: October 2022

Background and Aims

Although plastid genes are widely used in phylogenetic studies, signals of positive selection have been scarcely investigated in the grape family. The plastomes from 91 accessions of Vitaceae were examined to understand the extent to which positive selection is present and to identify which genes are involved. Moreover, the changes through time of genes under episodic positive selection were investigated and the hypothesis of an adaptive process following the Cretaceous–Palaeogene (K/Pg) transition about 66 million years ago was tested.

Methods

Different codon-substitution models were used to assess pervasive and episodic positive selection events on 70 candidate plastid genes. Divergence times between lineages were estimated and stochastic character mapping analysis was used to simulate variation over time of the genes found to be under episodic positive selection.

Key Results

A total of 20 plastid genes (29 %) showed positive selection. Among them, 14 genes showed pervasive signatures of positive selection and nine genes showed episodic signatures of positive selection. In particular, four of the nine genes (psbK, rpl20, rpoB, rps11) exhibited a similar pattern showing an increase in the rate of variation close to the K/Pg transition.

Conclusion

Multiple analyses have shown that the grape family has experienced ancient and recent positive selection events and that the targeted genes are involved in essential functions such as photosynthesis, self-replication and metabolism. Our results are consistent with the idea that the K/Pg transition has favoured an increased rate of change in some genes. Intense environmental perturbations have influenced the rapid diversification of certain lineages, and new mutations arising on some plastid genes may have been fixed by natural selection over the course of many generations.
Interactive effect between tree ageing and trunk-boring pest reduces hydraulics and carbon metabolism inHippophae rhamnoides
Authors: Wang Lin , Li Junpeng , Wang Yang , Xue Hao , Dai Yongxin , Han Youzhi
Published: October 2022

Sea-buckthorn (Hippophae rhamnoides) is widely distributed across the Eurasian continent. Recently sea-buckthorn has shown premature ageing and decline when confronted with water deficiency and Holcocerus hippophaecolus damage in northwest China and the Loess Plateau region. However, the physiological process of sea-buckthorn senescence in response to drought and pest damage is still unknown. In this study, 4-year-old (4y), 15-year-old normal growth (15yN) and 15-year-old seriously moth-damaged sea-buckthorn plants (15yH) were used as the research objects. The growth of branches and roots, branch water potential and percentage loss of conductivity (PLC), branch vulnerability to embolism (quantified by P50, xylem water potential at 50 % of PLC), branch xylem parenchyma cell viability, photosynthesis and the non-structural carbohydrate (NSC) content in branches and roots in dry and wet seasons were measured. The results showed that the length, basal diameter of 1-year-old branches and the leaf area of 4y trees were significantly larger than that of 15yN and 15yH trees, and the fine root density of 15yH trees was significantly lower than that of 15yN trees in all measured areas. The branch-specific hydraulic conductivity of 15yN and 15yH trees was only 50.2 % and 12.3 % of that of 4y trees, and the P50 of 4y, 15yH and 15yN trees was −3.69 MPa, −2.71 MPa and −1.15 MPa, respectively. The midday water potential and photosynthetic rate were highest in 4y trees, followed by 15yN and then 15yH trees in both the dry season and wet seasons, while branch PLC declined in the opposite direction (15yH trees highest, 4y trees lowest). The degree of PLC repair within a day was highest in 4y trees, followed by 15yN and then 15yH trees, and the viability of xylem cells was consistent with this pattern. The branch xylem starch and NSC content of 4y and 15yN trees were significantly higher than that of 15yH trees in the dry season, and the root starch and NSC content of 4y trees were significantly higher than that of 15yH trees in the two seasons. The above results suggest that the hydraulic properties of the normal elderly and seriously pest-damaged sea-buckthorn were significantly worse than in juvenile plants. Narrower early wood width and vessel density, high embolism vulnerability and weak embolism repair capacity led to the decline in water-conducting ability, and similarly further affected photosynthesis and the root NSC content. The decline in xylem parenchyma cell viability was the main reason for the limited embolism repair in the branches.
Variations in fungal and bacterial microbiome and chemical composition among fermenting Kishu-Narezushi batches
Authors: Kubo Miki , Niwa Ryo , Ohno Tomoki , Iwahashi Hitoshi
Published: October 2022

Kishu-Narezushi is a spontaneously fermented food comprising fish, rice, and salt. During spontaneous fermentation, the microbiome may differ among batches, even when manufactured in the same way. In addition, analyses of changes in the chemical composition of the product are important for clarifying flavor characteristics. We collected basic information on the microbiome and chemical composition of Kishu-Narezushi using multiple batches of fermentation and evaluated whether the microbiome was homogeneous. The fungal microbiome of Kishu-Narezushi was dominated by Saccharomycetales and Trichosporonales. The bacterial microbiome was diverse, although seven specific genera of lactic acid bacteria were identified. Glutamic acid, histidine, and serine levels decreased after ∼10 days of fermentation. Succinic acid, characteristic of Kishu-Narezushi, accumulated upon the consumption of glutamic acid. Though the microbiome was diverse, the chemical composition was similar among the batches.
DeepPerVar: a multi-modal deep learning framework for functional interpretation of genetic variants in personal genome
Authors: Wang Ye , Chen Li
Published: October 2022

Motivation

Understanding the functional consequence of genetic variants, especially the non-coding ones, is important but particularly challenging. Genome-wide association studies (GWAS) or quantitative trait locus analyses may be subject to limited statistical power and linkage disequilibrium, and thus are less optimal to pinpoint the causal variants. Moreover, most existing machine-learning approaches, which exploit the functional annotations to interpret and prioritize putative causal variants, cannot accommodate the heterogeneity of personal genetic variations and traits in a population study, targeting a specific disease.

Results

By leveraging paired whole-genome sequencing data and epigenetic functional assays in a population study, we propose a multi-modal deep learning framework to predict genome-wide quantitative epigenetic signals by considering both personal genetic variations and traits. The proposed approach can further evaluate the functional consequence of non-coding variants on an individual level by quantifying the allelic difference of predicted epigenetic signals. By applying the approach to the ROSMAP cohort studying Alzheimer’s disease (AD), we demonstrate that the proposed approach can accurately predict quantitative genome-wide epigenetic signals and in key genomic regions of AD causal genes, learn canonical motifs reported to regulate gene expression of AD causal genes, improve the partitioning heritability analysis and prioritize putative causal variants in a GWAS risk locus. Finally, we release the proposed deep learning model as a stand-alone Python toolkit and a web server.

Availability and implementation

https://github.com/lichen-lab/DeepPerVar.

Supplementary information

Supplementary data are available at Bioinformatics online.
Fritz Müller: 200 years of a pioneer evolutionist
Authors: Araujo Leonardo Augusto Luvison
Published: October 2022

Fritz Müller is known for explaining the evolutionary consequences of what is now called Müllerian mimicry, but his scientific contributions encompass a wide range of organisms and both ecological and evolutionary processes. His originality is seen in aspects as different as the discovery of the mutualistic nature of ant–fungus symbiosis, pioneering research in evolutionary developmental biology and the first mathematical treatment in a Darwinian framework. From his intimate knowledge of the natural history of Brazil and original observations of morphology and development, Müller provided evidence supporting natural selection. From the 20th century onwards, however, his scientific legacy has been re-examined only for single topics. To celebrate the bicentenary of his birth in 2022, this article briefly discusses his importance for current ecological and evolutionary knowledge.
In Living Color: Pigment-Based Microbial Ecology At the Mineral–Air Interface
Authors: Villa Federica , Wu Ying-Li , Zerboni Andrea , Cappitelli Francesca
Published: October 2022

Pigment-based color is one of the most important phenotypic traits of biofilms at the mineral–air interface (subaerial biofilms, SABs), because it reflects the physiology of the microbial community. Because color is the hallmark of all SABs, we argue that pigment-based color could convey the mechanisms that drive microbial adaptation and coexistence across different terrestrial environments and link phenotypic traits to community fitness and ecological dynamics. Within this framework, we present the most relevant microbial pigments at the mineral–air interface and discuss some of the evolutionary landscapes that necessitate pigments as adaptive strategies for resource allocation and survivability. We report several pigment features that reflect SAB communities’ structure and function, as well as pigment ecology in the context of microbial life-history strategies and coexistence theory. Finally, we conclude the study of pigment-based ecology by presenting its potential application and some of the key challenges in the research.
Focused ultrasound using a novel targeting method four-tract tractography for magnetic resonance–guided high-intensity focused ultrasound targeting
Authors: Feltrin Fabricio S , Chopra Rajiv , Pouratian Nader , Elkurd Mazen , El-Nazer Rasheda , Lanford Lauren , Dauer William , Shah Bhavya R
Published: October 2022

Magnetic resonance–guided high-intensity focused ultrasound thalamotomy is a Food and Drug Administration–approved treatment for essential tremor. The target, the ventral intermediate nucleus of the thalamus, is not visualized on standard, anatomic MRI sequences. Several recent reports have used diffusion tensor imaging to target the dentato-rubro-thalamic-tract. There is considerable variability in fibre tracking algorithms and what fibres are tracked. Targeting discrete white matter tracts with magnetic resonance–guided high-intensity focused ultrasound is an emerging precision medicine technique that has the promise to improve patient outcomes and reduce treatment times. We provide a technical overview and clinical benefits of our novel, easily implemented advanced tractography method: four-tract tractography. Our method is novel because it targets both the decussating and non-decussating dentato-rubro-thalamic-tracts while avoiding the medial lemniscus and corticospinal tracts. Our method utilizes Food and Drug Administration-approved software and is easily implementable into existing workflows. Initial experience using this approach suggests that it improves patient outcomes by reducing the incidence of adverse effects.
Shorter Linkable Ring Signature Based on Middle-Product Learning with Errors Problem
Authors: Lin Hao , Sun Shi-Feng , Wang Mingqiang , Liu Joseph K , Wang Weijia
Published: October 2022

DualRing is a novel generic construction introduced by Yuen et al. (CRYPTO’21), which can transform a special kind of (Type-T*) canonical identification scheme to a ring signature scheme. Compared with the classical approaches, this method can get a shorter signature. In this paper, we construct a new middle-product learning with errors (MPLWE)-based ring signature scheme by using this framework. Specifically, we propose a new MPLWE-based identification scheme, which is compatible with the DualRing, then we obtain a ring signature scheme by using DualRing framework. We also show how to achieve linkability from this ring signature by using a collision resistant hash function. In the end, we provide available parameter options for our (linkable) ring signature scheme. Under these parameters, the signature size of our linkable ring signature is $2-40 \times $ shorter (depending on the ring size) than the previous MPLWE-based scheme by Das et al. (Africacrypt’19).
Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn’s Disease
Authors: Chugh Rishika , Braga-Neto Manuel B , Fredrick Thomas W , Ramos Guilherme P , Terdiman Jonathan , El-Nachef Najwa , Loftus Edward V , Mahadevan Uma , Kane Sunanda V
Published: October 2022

Background

Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn’s disease [CD] in Phase 3 clinical trials.

Aims

Our goal was to describe our real-world experience with upadacitinib in CD.

Methods

This is a two-centre retrospective cohort study of adult patients with moderate to severe CD on upadacitinib. The primary outcome was clinical response and remission as determined by stool frequency and abdominal pain scores. Secondary endpoints included endoscopic response and remission as determined by change in Simple Endoscopic Score for CD. Outcomes were assessed at 3 months after starting upadacitinib and at the patient’s most recent follow-up. We further evaluated adverse events and dose-related response.

Results

A total of 45 CD patients received upadacitinib and were included in the safety analysis. Thirty-six patients received upadacitinib for CD, whereas nine received it for inflammatory arthritis [n = 8] or pyoderma [n = 1]. Thirty-three patients received upadacitinib for 3 months or longer and were included in the efficacy analysis. At the 3-month follow-up, 21 patients achieved clinical response [63.6%] and nine achieved clinical remission [27.2%]. At time of last follow-up, 23 patients had clinical response [69.7%], ten achieved clinical remission [30.3%] and four [28.6%] achieved endoscopic remission. Adverse events occurred in 12 patients [26.7%]. Two patients had a serious adverse event [4.5%] without associated mortality.

Conclusion

In this real-world cohort of highly refractory CD patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.
Placebo Response Rates in Randomized Controlled Trials for Perianal Crohn’s Disease: A Systematic Review and Meta-Analysis
Authors: Sharma Tanmay , Ma Christopher , Sedano Rocio , Hanzel Jurij , McDonald Cassandra , Hogan Malcolm , Kochhar Gursimran S , Narula Neeraj , Peyrin-Biroulet Laurent , Danese Silvio , MacDonald John K , Jairath Vipul
Published: October 2022

Background and Aims

Perianal fistulizing disease is a common complication of Crohn’s disease [CD], for which new therapies are urgently needed. To assist the design of clinical trials for novel therapeutics, we conducted a systematic review and meta-analysis of randomised controlled trials [RCTs] to quantify placebo rates and identify factors influencing them in perianal CD [pCD].

Methods

We searched MEDLINE, Embase and CENTRAL from inception to June 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for pCD. Placebo fistula response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics on point estimates.

Results

In 17 RCTs [13 induction, five maintenance] the pooled placebo fistula response and remission rate for induction trials was 25% (95% confidence interval [CI] 17–36%) and 17% [95% CI 11–25%], respectively. For maintenance trials, the pooled placebo fistula response and remission rate was 23% [95% CI 17–32%] and 19% [95% CI 14–25%], respectively. Trials enrolling patients with less disease activity and a higher proportion with ileal predominant disease were associated with significantly higher placebo response rates. Trials originating in Europe [compared to North America], therapies requiring perianal injection and a longer timepoint to measure remission were associated with higher placebo remission rates.

Conclusions

Placebo response and remission rates in pCD trials are influenced by patient and disease-related factors, as well as the type of intervention being studied. These contemporary rates will inform trial design for novel therapeutics.
Disease Activity and Health-related Quality of Life Relationships with Work Productivity in Patients with Ulcerative Colitis in OCTAVE Induction 1 and 2 and OCTAVE Sustain
Authors: Targownik Laura , Dubinsky Marla C , Steinwurz Flavio , Bushmakin Andrew G , Cappelleri Joseph C , Tai Elaine , Gardiner Sean , Hur Peter , Panés Julian
Published: October 2022

Background

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis [UC]. We evaluated the relationship between Mayo/Inflammatory Bowel Disease Questionnaire [IBDQ] scores and Work Productivity and Activity Impairment-UC [WPAI-UC] components in patients with UC.

Methods

All available pooled data from three Phase 3 tofacitinib studies [OCTAVE Induction 1 and 2 and OCTAVE Sustain] were included. Relationships were estimated using repeated measures regression models with Mayo score/subscores or IBDQ total/domain scores as a separate anchor predictor and WPAI-UC components as the outcome.

Results

Evidence for linear relationships was confirmed between Mayo/IBDQ scores and WPAI-UC components. Robust relationships between total Mayo score/IBDQ total score and WPAI-UC presenteeism, work productivity loss, and activity impairment were observed; relationships with absenteeism were weak. Total Mayo scores of 0 and 12 corresponded, on average, to WPAI-UC component scores of < 15% and ≥ 60%, respectively, and IBDQ total scores of 224 and 32 corresponded, on average, to WPAI-UC component scores of < 6% and ≥ 90%, respectively. Presenteeism, work productivity loss, and activity impairment [all 0–100%], respectively, improved on average by 14.7, 13.6, and 16.4 percentage points for every 3-point improvement in total Mayo score, and by 8.1, 7.9, and 8.8 percentage points for every 16-point improvement in IBDQ total score.

Conclusion

Robust relationships between Mayo/IBDQ scores with WPAI-UC presenteeism, work productivity loss, and activity impairment suggest that patient productivity and non-work activities are strongly associated with disease activity and HRQoL. The weak relationships with absenteeism suggest that patients attend work regardless of their disease activity/poor HRQoL.

ClinicalTrials.gov: NCT01465763;NCT01458951;NCT01458574.
A visual model of L2 motivation as a complex dynamic system
Authors: Pack Austin , Kiss Tamas
Published: October 2022

Learner motivation is an essential ingredient for successful language learning. This article investigates the motivating and demotivating factors affecting the motivation of fifty-eight EAP learners’ L2 learning. Guided by complex dynamic systems theory, with a dual focus on both what factors are important and what role these play in the L2 motivational system, this exploratory study utilized network analysis to map out how motivational factors connect to each other and form a L2 motivation factor network. It was found that motivating and demotivating factors, through the connections they share, exert an influence not only on each other, but on the whole motivational system. Based on the findings, suggestions are provided for classroom teachers for how they might steer learners’ motivational systems towards more motivated states, including introducing new factors into the system, enhancing connectivity, and increasing learners’ awareness of the complex and dynamic nature of motivation.
Orlando at play: the games of  Il palazzo incantato (1642)
Authors: Freitas Roger
Published: October 2022

Just before the denouement of the opera Il palazzo incantato, something remarkable happens. For long hours, the enchanted palace of the title—drawn from Ariosto’s Orlando furioso—has kept the 20-odd characters vainly searching for one another, with rarely more than two or three converging at a time. In the penultimate scene, however, the librettist, Giulio Rospigliosi, and composer, Luigi Rossi, allow nearly the entire company to assemble. But rather than greet and embrace each other, the long-lost lovers and friends suspend the story they have been enacting, abandon their characters’ motivations, and play a round of parlour games. The bizarre events of Act 3, scene 7—heretofore unremarked—illuminate something fundamental about the work as a whole. Indeed, notwithstanding its length and elaborate staging, this opera shows an affinity less with Rospigliosi’s earlier theatrical works than with the typical amusements of the aristocratic chamber, and with the cantata specifically: a difference that may stretch our idea of what an opera could be in Barberini Rome.
A large genome-wide association study of QT interval length utilizing electronic health records
Authors: Hoffmann Thomas J , Lu Meng , Oni-Orisan Akinyemi , Lee Catherine , Risch Neil , Iribarren Carlos
Published: October 2022

QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants. Conditional analysis identified 15 additional variants, 3 of which were novel. Little, if any, difference was seen when adjusting for putative QT interval lengthening medications genome-wide. Using multiple measurements in Genetic Epidemiology Research on Adult Health and Aging increased variance explained by 163%, and we show that the ≈6 measurements in Genetic Epidemiology Research on Adult Health and Aging was equivalent to a 2.4× increase in sample size of a design with a single measurement. The array heritability was estimated at ≈17%, approximately half of our estimate of 36% from family correlations. Heritability enrichment was estimated highest and most significant in cardiovascular tissue (enrichment 7.2, 95% CI = 5.7–8.7, P = 2.1e−10), and many of the novel variants included expression quantitative trait loci in heart and other relevant tissues. Comparing our results to other cardiac function traits, it appears that QT interval has a multifactorial genetic etiology.
Opioid Legislation in Patients With Inflammatory Bowel Disease: A State-wide Retrospective Cohort Study
Authors: Ahmed Waseem , Billing Wade , Stump Timothy E , Strobel Thomas , Sagi Sashidhar , Fischer Monika , Bohm Mathew
Published: October 2022

Background

Indiana State opioid prescription legislation has been shown to decrease overall opioid prescriptions. However, this effect has not been studied in specific diseases associated with chronic pain such as inflammatory bowel disease (IBD). We aimed to determine the effect of state opioid prescription legislation on opioid prescribing patterns in IBD.

Methods

A retrospective cohort analysis using an interrupted time-series from December 15, 2010 to July 1, 2018, with 2 time periods separated by Title 844 of the Indiana Administrative Code, in a statewide health care system capturing the majority of the state’s population including all adult patients with IBD. The primary outcome was opioid prescription rate per person-year.

Results

In total, 9436 patients met inclusion criteria. After legislation, the total number of opioid orders per patient-year continued to increase (0.543, 95% CI, 0.528-0.558, to 0.663, 95% CI, 0.654-0.672), with fewer scripts from the emergency department (0.113, 95% CI, 0.106-0.120, to 0.092, 95% CI, 0.088-0.095) and more from outpatient providers (0.303, 95% CI, 0.292-0.314 to 0.432, 95% CI, 0.424-0.439). There were increases in biologic (0.206, 95% CI, 0.197-0.215 to 0.517, 95% CI, 0.509-0.525) and steroid (0.182, 95% CI, 0.173-0.190 to 0.237, 95% CI, 0.232-0.243) prescriptions per person-year following legislation. Factors associated with heavy opioid use included chronic steroids (odds ratio, 5.030; 95% CI, 4.176-6.054), history of IBD-related surgery (odds ratio, 2.807; 95% CI, 2.367-3.323) and current smoking (odds ratio, 2.650; 95% CI, 2.223-3.158).

Conclusions

Despite legislation and the increased use of disease-modifying drugs, statewide opioid prescriptions continued to increase. The increase in opiate use, high steroid use, and significant health care utilization suggests poor underlying disease control.
HIV-1 genetic diversity and transmitted drug resistance to integrase strand transfer inhibitors among recently diagnosed adults in Porto Alegre, South Brazil
Authors: Nunes Cynara Carvalho , Sita Alexandre , Mallmann Larissa , Birlem Gabriela Espindola , de Mattos Larissa Gomes , Da Silva Daila Haemk , Furlanetto Karen Oliveira , Hansen Alana Witt , De Almeida Paula Rodrigues , Fleck Juliane Deise , Spilki Fernando Rosado , de Matos Almeida Sabrina Esteves , Weber Matheus Nunes
Published: October 2022

Objectives

The HIV-1 genetic diversity and the presence of transmitted drug resistance mutations (TDRMs) against integrase strand transfer inhibitors (INSTIs) were assessed sequencing samples of antiretroviral (ARV)-naive HIV-1-infected individuals from South Brazil.

Methods

Viral RNA from 42 ART-naive individuals was submitted to complete HIV-1 integrase gene amplification by RT–PCR and sequencing.

Results

Viral strains carrying TDRMs against INSTIs were not detected in the present study. However, the polymorphisms L74M and L74I were each observed in 4.8% of the individuals. These accessory mutations have been reported as putative causes of TDRMs in ART with raltegravir, but only when associated with additional major mutations. When submitted to HIV-1 subtyping, 50% were classified as subtype C, 21% as recombinant BC, 19% as subtype B, 4.8% as subtype F1 and 4.8% as recombinant CF1.

Conclusions

All 42 ARV-naive individuals were apparently susceptible to INSTIs, included in the Brazilian therapeutic guideline since 2009. To the best of our knowledge, this is the first study to evaluate TDRMs against INSTIs in Brazil. The most prevalent HIV-1 subtypes were subtype C, followed by the recombinant BC and subtype B, which is in agreement with previous studies. However, the presence of subtype F1 and recombinant CF1 reported herein was not observed in previous studies.
Characteristics of the sore throat test and treat service in community pharmacies (STREP) in Wales: cross-sectional analysis of 11 304 consultations using anonymized electronic pharmacy records
Authors: Mantzourani Efi , Wasag Diana , Cannings-John Rebecca , Ahmed Haroon , Evans Andrew
Published: October 2022

Background

An NHS-funded sore throat test and treat (STTT) service was introduced in selected community pharmacies in Wales. Service users were screened using FeverPAIN/Centor scores, offered rapid antigen detection testing (RADT) to detect group A Streptococcus if appropriate, and supplied with antibiotics (by the pharmacist) if indicated. Following an initial evaluation, the service was rolled out nationally.

Objectives

This study forms part of the long-term STTT evaluation. The aim was to describe characteristics of the service and service users, the delivery, service outcomes, patient safety and antibiotic prescribing.

Methods

Cross-sectional descriptive study using anonymized individual-level data from electronic pharmacy records of all eligible STTT service users between November 2018 and February 2020.

Results

We identified 11 304 pharmacy STTT consultations in service users aged 6 years and over, with a median age of 25 years (IQR: 12 to 44). RADT was undertaken in 8666 (76.7%) consultations with 2503 (28.9% of RADT) positive tests. In total, 2406 (21.3%) service users were supplied with antibiotics. Pharmacists managed 91% of consultations in the pharmacy and referred only 937 (9.3%) service users to a GP and 27 (0.2%) to the Emergency Department. Higher rates of antibiotic supply were observed in out-of-hours consultations when compared with in-hours (24.9% versus 20.9%).

Conclusions

This is the largest description of a pharmacy-led STTT service to date and suggests it can be delivered at scale to align with a pre-specified pathway that promotes appropriate use of RADT and antibiotics. The service could substantially reduce workload from a common illness in other heavily pressurized areas of primary and emergency care.
Analysing the efficacy and tolerability of dolutegravir plus either rilpivirine or lamivudine in a multicentre cohort of virologically suppressed PLWHIV
Authors: Ciccullo A , Baldin G , Borghi V , Cossu M V , Giacomelli A , Lagi F , Farinacci D , Iannone V , Passerotto R A , Capetti A , Sterrantino G , Mussini C , Antinori S , Di Giambenedetto S
Published: October 2022

Objectives

We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine.

Methods

We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters.

Results

We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014).

Conclusions

Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.
127 Large Scale Practical Nutrition Research Sharing: Nursery Nutrition Research and Nutritional Technologies and Strategies to Reduce Morbidity and Mortality
Authors: Mendoza Omarh , Shull Caleb M
Published: October 2022

In modern swine production, there is a heightened interest surrounding the nutrition of the young pig as a result of the necessity of nursery pig nutrition programs to evolve, due to the inevitability of stress during the weaning event and the growing challenges experienced in commercial pig operations at this stage of production. Therefore, it is no longer sufficient to design a nutrition program that focuses solely on delivering the right nutrients for a pig at weaning that maximizes growth performance during the nursery period, as this may not result in desired outcomes from weaning to harvest. Consequently, nursery programs are being further enhanced with a renewed focus on nutritional technologies and strategies that emphasize feed intake, but more importantly, that maximize the probability of livability in the nursery. However, there is a growing need for large scale practical research that evaluates these nutritional technologies and strategies, since most of the published research has been done with a limited number of animals that limits the ability to detect mortality differences. Thus, this research will require a different model compared to that which has been used historically for nursery nutrition research. Some of the key elements of this research model include experimental design with the appropriate statistical power to detect mortality differences, in addition to conducting the experiments in conditions that are similar to the management and environment that resembles commercial production specific to the system, among others. To that end, it will be the objective of this presentation to share some of the large-scale research focused on minimizing disruption of nutrient intake using nutritional technologies that are supplementary to typical nursery diets, offering the potential to reduce morbidity and mortality of pigs raised on wean-to-market facilities.
86 Reaching Genetic Potential in Pigs: 10 Disruptive Digital Technologies
Authors: Connolly Aidan J
Published: October 2022

Consumer (‘prosumer’) concerns over animal welfare and the environmental footprint of pork production dominate the media. Indeed, the discussion of alternatives to pork, both from the continued global growth in chicken consumption and advances in cellular meat production and vegetable protein alternatives, represent real threats to pork’s future. Producers and processors continue to focus genetic improvement, nutrition, and management to improve meat production efficiency. Disease mitigation and animal health limit our ability to reach the pigs genetic potential, either in terms of pigs processed per sow, or breaching the 2:1 lifetime feed conversion. Can farmers continue to gain more pigs per sow, while keeping them healthy and alive? How do we maximize meat yield per carcass without losing flavor and the consumer experience? Are there limits to how low we can go in the conversion of nutrients into feed? Despite increased consumer demands and the continued need to improve production efficiency, the management of pigs has changed little in the last decades, often relying on decades old innovations and enhanced biosecurity. Innovations such as vertical hog farms in China, muti site production, and new feed technologies offer incremental but not disruptive improvements. The 10 digital technologies (PWC) is a useful framework to review the technologies with the potential to transform swine production. These are 3D Printing, Internet of Things, Artificial Intelligence, Data Analytics, Cloud Computing, Robotics, Drones, Blockchain, Virtual Reality and Augmented Reality (‘Metaverse’). Concepts such as precision nutrition, precision management recognize the need for better data, and data underpins advances such as nutrigenomics, microbiota and the environment of the pig. Digital technologies can disrupt pork production while offering the opportunity to respond to consumers, legislators, producer demands and other actors within the pork production chain.
6 Evaluating the Impacts of Starvation on Permethrin Resistant and Susceptible Horn Flies (Diptera: Muscidae)
Authors: Ramirez Jovannah , Sanchez-Sandoval Ulises A , Figueroa-Zamudio Joaquin J , Walker Hannah L , Smythe Brandon G
Published: October 2022

The objective of the current study is to evaluate the impact of induced starvation on horn fly susceptibility to permethrin and general reproduction using filter paper and manure bioassays, respectively. Incorporating push-pull systems for horn fly control has recently gained much attention for use in managing this pest. However, the consequences of temporary starvation associated with the relocation of horn flies from one host to another have yet to be fully explored. Susceptible (SS) and permethrin resistant (PR) horn flies were randomly allocated to one of four treatment groups: 1- blood fed, 2- partially starved (4hr), 3- moderately starved (8hr), and 4- severely starved (12hr). Permethrin resistant flies were 1,227 times more (P < 0.05) tolerant to permethrin in comparison to SS flies. Furthermore, SS blood fed flies were 1.18, 1.89, and 3.12 times more tolerant to permethrin than SS flies starved for 4, 8, and 12 hours, respectively. Egg hatching rates decreased (P < 0.04) for 8hr and 12hr starved flies in comparison to blood fed flies. Larval development, as measured through manure bioassays was lower (P = 0.02) in severely starved flies in comparison to blood fed flies. Pupae sizes were unaffected (P = 0.58) by starvation and fly strain. These results indicate that susceptibility to permethrin increases as time without a blood meal increases and furthermore, offspring success is reduced specifically through egg viability. Findings from this work will help further expand current integrated pest management options for animal producers by increasing our understanding and implementation of push-pull strategies in animal production systems.
PSI-6 The Influence of a Single Administration of Prostaglandin on Estrus Synchronization in Range Sheep Production
Authors: Gallacher Kristie L , Dunlap Richard L , Cox Shad H , Andrews Taylor N , Melchior Emily A , Summers Adam F
Published: October 2022

Administration of a single injection of prostaglandin after ram introduction has previously been reported as an effective method to synchronize estrus in ewes housed in a dry lot setting. The objective of this study was to investigate the effectiveness of a single injection of prostaglandin administered at the beginning of the breeding season after ram introduction, on estrus synchronization in range ewes. Western Whiteface cross ewes, of which thirty-six were ½ blood South African Meat Merino (SAMM) and seventeen ¼ blood SAMM (total n=53) were assigned to one of two treatments: control (CON; n=26) or one injection of prostaglandin (PG; n=27). Ewes were utilized in a complete randomized block design and were stratified by SAMM percentage, body condition score (BCS) and age. Ewes assigned to PG treatment were administered 3 mL of prostaglandin IM (Lutalyse, Zoetis Animal Health) approximately 60 h after rams were introduced with ewes. Rams (n=4) were applied with marking paint and placed with ewes on (d 0: December 21) and remained for the duration of the 56 d breeding season for natural service. Ewes were observed for estrus twice daily at 0730 h and 1700 h for d 0-10 and d 16-21 of the breeding season, by an experienced evaluator. At lambing, birth weight, sex, and type of birth was recorded. The MIXED and GLIMMIX procedures of SAS were used to analyze estrus response, ewes bred in the first 5 d of the breeding season, days to lambing, lambing date, number of lambs born, and lamb weight. South African Meat Merino percentage was included as an independent variable but was found to be nonsignificant and was removed from the statistical model. The proportion of ewes bred during the first 5 d of the breeding season was not different among the two treatments (P ≥ 0.60). There was no difference between the PG ewes and the CON ewes for the date of estrus (P ≥ 0.82). There was no difference between the PG ewes and the CON ewes for the lambing date (P = 0.60). Treatment did not influence days to lambing (P ≥ 0.25). The number of lambs born per ewe tended to be influenced by treatment (P < 0.08), with PG ewes tending to have more lambs than CON ewes. Lamb weights were not different among treatments (P ≥ 0.50). In conclusion, the administration of a single PG injection after ram exposure did not influence estrus expression, days to lambing, or lambing date, however, PG ewes did tend to have more lambs.
PSII-2 Effect of Protein Supplementation Level and Degradability on Forage Utilization by Steers Consuming Low-Quality Forage: I. Bos taurus taurus
Authors: Cox Jodi R , Koy Kali K , Wickersham Tryon A
Published: October 2022

A deficiency of ruminally available N (RAN) caused by a basal diet of low-quality forage may depress forage utilization. Supplemental protein improves utilization by increasing RAN therefore increasing intake and potentially improving digestibility. The objective of this study was to determine the effect of ruminal degradability and level of protein supplementation on forage utilization by Bos taurus taurus steers. Accordingly, six ruminally cannulated Angus steers (BW 294 ± 37.7 kg) were used in a 5×5 Latin square to evaluate the interaction between level and degradability of protein supplementation when consuming King Ranch Bluestem hay (3.5% CP, 71.0% NDF). Treatments were arranged as a 2×2 factorial with steers receiving protein supplements (43% CP) with two levels of protein degradability (35 or 70% RDP) fed at two levels of supplementation, providing 1.26 or 2.53 g/kg BW (LOW and HIGH). A control treatment (CON) provided no supplemental protein. Five 14-d periods were conducted, consisting of 9 d adaptation and 4 d to measure intake and digestion, and 1 d for ruminal fermentation. No degradability × level interactions were significant for any measures of intake or digestion, although there was a tendency for an interaction (P = 0.09) for total organic matter intake (TOMI), resulting from a tendency for a quadratic (P = 0.08) increase when supplemented. In contrast, the 70% RDP supplement continued to increase TOMI linearly (P < 0.01), suggesting the maximum effective level of supplementation was not reached. As expected, protein supplementation increased all measures of intake such as, forage OMI (FOMI), total digestible OMI (TDOMI), and NDF intake (P < 0.01). In addition, level of supplementation affected all measures of intake (P ≤ 0.01) with HIGH being greater than LOW. Protein supplements with 70% RDP at LOW increased FOMI 28% versus control when supplemented at LOW, and 47% at HIGH. Supplementation with 35% RDP increased FOMI 23% at the LOW and 28% at HIGH indicating the lower degradability supplement was less effective at improving forage utilization that the 70% RDP supplement (P = 0.01). Total NDF intake (NDFI) followed this same pattern with 70% RDP supplementation increasing NDFI 29 and 52% with LOW and HIGH supplementation, respectfully; 28 and 37% when 35% RDP supplementation was provided (P = 0.10). Despite the effect of protein supplementation on intake, OM digestion (OMD) and NDF digestion (NDFD) were not affected by protein supplementation regardless of degradability or level (P ≥ 0.23). In conclusion, FOMI and TDOMI were increased with the provision of greater levels and more degradable supplements resulting in better forage utilization.
PSII-3 Effect of Protein Supplementation Level and Degradability on Forage Utilization by Steers Consuming Low-Quality Forage: II. Bos taurus indicus
Authors: Cox Jodi R , Koy Kali K , Wickersham Tryon A
Published: October 2022

A deficiency of ruminally available N (RAN) caused by a basal diet of low-quality forage may depress forage utilization. Supplemental protein improves utilization by addressing the RAN therefore increasing intake and potentially improving digestibility. The objective of this study was to determine the effect of ruminal degradability and level of protein supplementation on forage utilization by Bos taurus indicus steers. Accordingly, five ruminally cannulated Brahman steers (BW 369 ± 51 kg) were used in a 5 × 5 Latin square to evaluate the interaction between level and degradability of protein supplementation when consuming a basal diet of King Ranch Bluestem hay (3.5% CP, 71.0% NDF). Treatments were arranged as a 2 × 2 factorial with steers receiving protein supplements (43% CP) having two levels of protein degradability (35 or 70% RDP) fed at two levels of supplementation, 1.26 or 2.53 g/kg BW (LOW and HIGH). A control treatment providing no supplemental protein was also included (CON). Five 14-d periods were conducted, consisting of 9 d adaptation, 4 d to measure intake and digestion, and 1 d for ruminal fermentation. No degradability × level interactions were observed for any measures of intake or digestion (P > 0.10). Protein supplementation linearly increased (P < 0.01) total digestible OM intake (TDOMI), NDF intake (P = 0.01), and total digestible NDF intake (DNDFI; P < 0.03). Total digestible OMI was greater in steers receiving 70% RDP than the 35% RDP (P = 0.08). This response resulted from the linear increase in FOMI with 75% RDP (P = 0.03), that was not observed with 35% RDP. Despite differences in FOMI, TDOMI increased linearly (P ≤ 0.03) for both 35 and 70% RDP, partially the result of providing a highly digestible supplement. Forage OMI differences also resulted in NDFI being greater for 70% RDP than 35% RDP (P = 0.06) and DNDFI increasing linearly with the addition of both supplements (P ≤ 0.03). Organic matter digestibility (OMD) increased linearly with supplementation as a result of supplement provision. In contrast to observations previously reported in Bos taurus steers, provision of 35% RDP supplement did not improve FOMI. Supplementation with 70% RDP improved FOMI 19 and 20% compared to the basal diet at LOW and HIGH levels, respectively. A portion of this relatively modest response to protein supplementation could be attributed to greater intake in the unsupplemented controls.