bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a two-layer dense-pixel LYSO Compton camera prototype for prompt gamma imaging
Authors: Yao Zhiyang , Xiao Yongshun , Dong Minghao , Deng Heng
Published: January 2023

Objective. Lutetium–yttrium orthosilicate (LYSO)-based Compton camera (CC) has been proposed for prompt gamma imaging due to its high detection efficiency and position resolution. However, very few LYSO CC prototypes have been built and used for practical evaluation. In this study, we built a lightweight dense-pixel silicon photomultiplier-based two-layer LYSO CC prototype for future prompt gamma imaging. Approach. We attempt the first-ever effort to use the double-encoding with the thick light guide and coding circuit structure for 46 × 46 dense-pixel LYSO detectors construction and use pixel segmentation based on centroid mapping to obtain 4232 spectral calibrations. We also present a framework for list-mode projection data acquisition based on the decoding of the time series data obtained by data acquisition card in this study. Finally, the standard source calibration, ring-like 22Na source with non-uniform intensity, and mixed point-like source with a wide energy spectrum experiments were implemented to evaluate the resolution metrics and imaging performance of the prototype. Main results. The lateral position resolution of the prototype was 1 mm, and the maximum measurement deviation is 2.5 mm and 5 mm in the depth direction for the scatterer and absorber, respectively. In the experiments, the measured energy resolution was 9.63% @ 1.33 MeV for the scatterer and 10.8% @ 1.33 MeV for the absorber. And the detection efficiency of the prototype for a spherical 60Co source with a diameter of 2.8 mm at 10 cm far was 5.7 × 10−3 @ 1.33 MeV and the full width at half maximum of the reconstruction was 5.5 mm. Besides, the spatial position offset within 2 mm of the radioactive source at 10 cm can be distinguished. Signification. The developed two-layer dense-pixel LYSO CC contributes to incorporating Compton imaging techniques for prompt gamma detection and multiple energy sources into nuclear medical imaging.
Lignin precipitation-driven fabrication of gradient porous hydrogel actuator with temperature response
Authors: Chen Ying , Kuang Peipei , Shen Xiaochen , Lv Xiaowei , Wang Yushu , Yin Weihan , Zou Tongqing , Wang Ben , Liu Yupeng , Fan Quli
Published: January 2023

An operative and straightforward precipitation-driven approach was reported to fabricate an anisotropic hydrogel actuator with temperature response. Through in situ deposition of lignin nanoparticles (LNP) in the process of polyacrylamide (PAM) polymerization with the presence of hydroxypropyl cellulose (HPC), an inhomogeneous hydrogel network (PAM/HPC/lignin hydrogel, PHL hydrogel) with distinct gradient porous structure was achieved that could be tailored to form a hydrogel actuator. The PHL hydrogels exhibit faster shape deformation as responding to temperature and higher mechanical properties caused by introducing the LNP and HPC chains. The deformation direction and rate of the hydrogel actuator could be influenced by the lignin content, temperature, and as well as their shape. The maximum bending angle could reach near 360° with 60 s as it was exposed to 60 °C. Due to the excellent bending behavior of the PHL hydrogel, the potential applications as grippers and valves were studied, and the results showed its sensitive response to temperature, suggesting its potential application as an intelligent actuator in the future.
Vortex glass phase transition in two-dimensional Bi2Sr2Ca2Cu3O

10+δ

sub-microbridge
Authors: Yu Aobo , Zhang Tianzhu , Fan Donghui , Yuan Pusheng , Peng Wei , Li Hao , Lin Chengtian , Mu Gang , Zhang Xiaofu , You Lixing
Published: January 2023

Vortex dynamics is crucial for practical applications and to understand the nature of the mixed state for high-T

c
superconductors. Mechanically exfoliated ultra-thin single crystals provide a unique platform for exploring vortex physics in the two-dimensional (2D) limit. Here, we systematically investigated the current–voltage (I–V) characteristics as functions of the temperature and magnetic field in a single-crystalline Bi2223 sub-microbridge of 2.5 unit cells thickness. The nonlinear I–V characteristics are excellently described by the scaling theory for a quasi-2D vortex glass (VG) phase transition, and a phase diagram revealing the VG and vortex liquid phase is drawn. The scaling parameter v is consistent with previous reports, while the critical exponent z is far smaller than that in most investigations. Moreover, the VG transition temperature T

g
of the present sample is higher than that in the reported Bi2223 epitaxial thin films and tapes. In addition, the pinning force density of our sample is calculated, which is stronger than that reported in Bi2223 epitaxial thin films and tapes. Our results indicate that a high pinning force density may suppress the dynamical critical exponent z and enhance the VG phase transition temperature, providing new insight into the flux dynamics in cuprates.
Skin microvasculature determined using OCT angiography: first evidence of its relation with aging
Authors: Barrera-Patiño C P , de Oliveira Lucas Orlandi , Mattos Vicente Silva , Stringasci Mirian Denise , Requena Michelle Barreto , Bagnato Vanderlei Salvador
Published: January 2023

The human skin changes with time, presenting different appearances and even properties. Peripheral vascularization is one of the crucial factors that affect skin growth. The variation of vascularization with age is a topic that always arouses great interest. The quality of the skin, concerning age, can be an important factor in interventions for functional skin improvement and understanding the skin-related aging process. In particular, the statistical distribution of the size of peripheral vascularization components and their indicators of evolution with age is a quantifier that is not common in conventional medicine. Their introduction is the main objective of this report. In this work, we use optical coherent tomography angiography to investigate skin microvasculature changes in men and women from different age groups. Using our algorithms, we were able to assess the vessel density and the distribution of average vessel caliber as a function of age. The vessel’s density distribution shifts to smaller vessels’ diameters values according to aging. This finding may indicate a way of evaluating physiological skin aging and proposing alternatives for its delay. Some possible consequences of these findings are also discussed.
Acne vulgaris: navigating the National Institute for Health and Care Excellence recommendations for specialist referral, patient expectations and the isotretinoin product licence
Authors: Khalil Nada , Patel Neil P
Published: January 2023

Oral isotretinoin is a highly effective drug for severe acne but with ongoing serious safety concerns and we are cautiously reminded by the Medicines and Healthcare products Regulatory Authority to prescribe this drug within licence. We review the National Institute for Health and Care Excellence recommendations for considering referral of acne to specialist care and propose some improvements. This may help manage patient expectations of treatment, ensure only appropriate patients are seen in secondary care and help prescribers remain within the isotretinoin product licence.
Thinking aloud in clinical teaching of dermatology: an old school method?
Authors: Salava Alexander
Published: January 2023

Clinical dermatology is primarily learned through example or model learning. Here a method of teaching dermatology by thinking aloud is described that may improve learning outcomes and student motivation.
Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia
Authors: Tschaidse Lea , Reisch Nicole , Arlt Wiebke , Brac de la Perriere Aude , Linden Hirschberg Angelica , Juul Anders , Mallappa Ashwini , Merke Deborah P , Newell-Price John D C , Perry Colin G , Prete Alessandro , Rees D Aled , Stikkelbroeck Nike M M L , Touraine Philippe A , Coope Helen , Porter John , Ross Richard John M , Quinkler Marcus
Published: January 2023

Objective

Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist.

Design

We investigated the renin–angiotensin–aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy.

Methods

Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus standard GC therapy (n = 41). MC replacement therapy remained unchanged throughout the study. Blood pressure, serum potassium, serum sodium, plasma renin activity (PRA), and serum 17OHP and androstenedione concentrations were analyzed at baseline, 4, 12, and 24 weeks.

Results

The median serum 17OHP in the morning was significantly lower on MR-HC compared with standard GC at 24 weeks (2.5 nmol L–1 (IQR 8.3) versus 10.5 nmol L–1 (IQR 55.2), P = .001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 ng L–1 s–1 (IQR 1.0) to 0.48 ng L–1 s–1 (IQR 0.61), P = .012) but not in patients on standard GC (0.53 ng L–1 s–1 (IQR 0.66) to 0.52 ng L–1 s–1 (IQR 0.78), P = .613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol L–1 to 139.3 ± 1.8 mmol L–1, P = .047), but remained unchanged on standard GC (139.8 ± 1.6 mmol L–1 to 139.3 ± 1.9 mmol L–1, P = .135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels.

Conclusion

6 months of MR-HC therapy decreased PRA and increased sodium levels indicating a greater agonist action of the 9α-fluorocortisol dose, which may be due to the decreased levels of the MC-receptor antagonist 17OHP.
The management of postoperative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients
Authors: Calabrese Anna , Puglisi Soraya , Borin Chiara , Basile Vittoria , Perotti Paola , Pia Anna , Berchialla Paola , Volante Marco , Fiori Cristian , Porpiglia Francesco , Veltri Andrea , Reimondo Giuseppe , Terzolo Massimo
Published: January 2023

Objective

The management of adrenocortical carcinoma (ACC) recurrences remains controversial, and we present herein our experience with postoperative ACC recurrences.

Design and methods

Retrospective analysis in a single reference center of 106 patients with ACC recurrence.

Results

The median follow-up was 45 months, the median recurrence-free survival (RFS) 12 months (IQR 6-23), and the median overall survival (OS) 45 months (IQR 29-75). ACC recurrences occurred as a unique lesion (group A) in 35.8%, multiple lesions in a single organ (group B) in 20.8%, and affecting multiple organs (group C) in 43.4% of patients. Baseline characteristics of patients stratified by the type of recurrence did not differ between them, except RFS, which was significantly longer in group A. Locoregional treatments were used in 100% of patients of group A, 68.2% in group B, and 26.1% in group C. After treatment of recurrence, 60.4% of patients became free of disease attaining a second RFS of 15 months (IQR 6-64). Margin status RX and R1, percent increase in Ki67, and recurrence in multiple organs were associated with an increased risk of mortality, while adjuvant mitotane treatment and longer time to first recurrence were associated with reduced risk. Recurrence in multiple organs and systemic treatment of recurrence had a negative impact on survival from the treatment of recurrence.

Conclusions

This study shows that patients with ACC have a better prognosis when the disease recurs as a single lesion and supports the use of locoregional treatments to treat disease recurrence.
The far-right and anti-vaccine attitudes: lessons from Spain’s mass COVID-19 vaccine roll-out
Authors: Serrano-Alarcón Manuel , Wang Yuxi , Kentikelenis Alexander , Mckee Martin , Stuckler David
Published: January 2023

Background

Far-right politicians in several countries have been vocal opponents of COVID-19 vaccination. But can this threaten vaccine roll-out?

Methods

We take advantage of repeated cross-sectional surveys with samples of around 3800 individuals across Spain conducted monthly from December 2020 to January 2022 (n = 51 294) to examine any association between far-right politics and vaccine hesitancy through the whole vaccine roll-out.

Results

Consistent with prior data, we found that far-right supporters were almost twice as likely to be vaccine-hesitant than the overall population in December 2020, before vaccines became available. However, with a successful vaccine roll out, this difference shrank, reaching non-significance by September 2021. From October 2021, however, vaccine hesitancy rebounded among this group at a time when the leadership of the far-right promoted a ‘freedom of choice’ discourse common among anti-vax supporters. By the latest month analysed (January 2022), far-right voters had returned to being twice as likely to be vaccine-hesitant and 7 percentage points less likely to be vaccinated than the general population.

Conclusions

Our results are consistent with evidence that far-right politicians can encourage vaccine hesitancy. Nonetheless, we show that public attitudes towards vaccination are not immutable. Whereas a rapid and effective vaccine rollout can help to overcome the resistance of far-right voters to get vaccinated, they also seem to be susceptible to their party leader’s discourse on vaccines.
Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period
Authors: Föhr Tiina , Waller Katja , Viljanen Anne , Rantanen Taina , Kaprio Jaakko , Ollikainen Miina , Sillanpää Elina
Published: January 2023

Background

Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality.

Methods

We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality.

Results

During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive.

Conclusions

The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality.
Maximizing the forecasting skill of an ensemble model
Authors: Herrmann Marcus , Marzocchi Warner
Published: January 2023

An ensemble model integrates forecasts of different models (or different parametrizations of the same model) into one single ensemble forecast. This procedure has different names in the literature and is approached through different philosophies in theory and practice. Previous approaches often weighted forecasts equally or according to their individual skill. Here we present a more meaningful strategy by obtaining weights that maximize the skill of the ensemble. The procedure is based on a multivariate logistic regression and exposes some level of flexibility to emphasize different aspects of seismicity and address different end users. We apply the ensemble strategy to the operational earthquake forecasting system in Italy and demonstrate its superior skill over the best individual forecast model with statistical significance. In particular, we highlight that the skill improves when exploiting the flexibility of fitting the ensemble, for example using only recent and not the entire historical data.
Gap-free genome assembly and comparative analysis reveal the evolution and anthocyanin accumulation mechanism of Rhodomyrtus tomentosa
Authors: Li Fangping , Xu Shiqiang , Xiao Zitong , Wang Jingming , Mei Yu , Hu Haifei , Li Jingyu , Liu Jieying , Hou Zhuangwei , Zhao Junliang , Yang Shaohai , Wang Jihua
Published: January 2023

Rhodomyrtus tomentosa is an important fleshy-fruited tree and a well-known medicinal plant of the Myrtaceae family that is widely cultivated in tropical and subtropical areas of the world. However, studies on the evolution and genomic breeding of R. tomentosa were hindered by the lack of a reference genome. Here, we presented a chromosome-level gap-free T2T genome assembly of R. tomentosa using PacBio and ONT long read sequencing. We assembled the genome with size of 470.35 Mb and contig N50 of ~43.80 Mb with 11 pseudochromosomes. A total of 33 382 genes and 239.31 Mb of repetitive sequences were annotated in this genome. Phylogenetic analysis elucidated the independent evolution of R. tomentosa starting from 14.37MYA and shared a recent WGD event with other Myrtaceae species. We identified four major compounds of anthocyanins and their synthetic pathways in R. tomentosa. Comparative genomic and gene expression analysis suggested the coloring and high anthocyanin accumulation in R. tomentosa tends to be determined by the activation of anthocyanin synthesis pathway. The positive selection and up-regulation of MYB transcription factors were the implicit factors in this process. The copy number increase of downstream anthocyanin transport-related OMT and GST gene were also detected in R. tomentosa. Expression analysis and pathway identification enriched the importance of starch degradation, response to stimuli, effect of hormones, and cell wall metabolism during the fleshy fruit development in Myrtaceae. Our genome assembly provided a foundation for investigating the origins and differentiation of Myrtaceae species and accelerated the genetic improvement of R. tomentosa.
Menopause at Work: An Analysis of the Current Law and Proposals for Reform
Authors: Myhill Katie , Sang Kate
Published: January 2023

This article seeks to review the intersection between menopause and employment law, summarising existing protections and analysing key case law. The study finds that existing protections are limited in their efficacy in protecting individuals experiencing menopausal symptoms from detriment and discrimination in the workplace. Indeed, whilst individuals may be able to raise claims for menopausal discrimination under the Equality Act 2010, the lack of clarity as to which of the protected characteristics such a claim should be raised against and the apparent lack of consistency in the case law further serves to undermine the protections which currently exist. Whilst a number of proposals have been put forward as to how the law may be adapted or created to improve protections for those subject to menopausal discrimination, careful consideration will be needed to ensure any such reforms do not inadvertently result in an increased stigmatisation of menopausal women and the undermining of efforts to improve gender equality at work. However, what is clear from an analysis of the law is that menopause is not simply a ‘women’s health issue’, it is also a workplace issue which employers can no longer afford to ignore.
P03 Identification of intervention opportunities through assessment of the appropriateness of antibiotic prescribing in surgical patients in a UK hospital using a national audit tool: a single centre retrospective audit
Authors: Hearsey D , Bamford K , Hutton M , Wade L , Coates H , Ramsay E , Alberts B A , Powell N
Published: January 2023

Background

Identifying opportunities to safely reduce antibiotic prescribing is necessary for prescribers and antibiotic stewardship teams to minimize unwarranted antibiotic use. We aimed to quantify excess antibiotic use in General Surgery.

Methods

We retrospectively audited the antibiotic prescribing for patients discharged from the General Surgery specialty in an acute hospital in the south-west of England between 01/08/21 and 31/08/21 using an audit tool developed by Public Health England. The appropriateness of prescribing was determined for each patient at three antibiotic decision time-points: at initiation, the pre-72h antibiotic review, and treatment duration. Two infection specialists and a general surgeon reviewed each patient. Indication and excess days of therapy (DOTs) were calculated at each decision time-point and expressed as a proportion of total DOTs.

Results

Eighty-six patients were prescribed 1162 DOTs; 192 (16.5%) excess DOTs were prescribed in 38 patients (44%), with zero excess days identified in the remaining 48 patients (56%). Seventy-five of 192 (39%) excess DOTs occurred at initiation; 55/192 (29%) after the pre-72hour antibiotic review; and 62/192 (32%) due to protracted antibiotic courses. There was concordance between the general surgeon and infection specialist for the majority of apportioned excess DOTs. However, the surgeon apportioned fewer excess DOTs 160/1162 (13.8%). Overall IV antibiotics accounted for 53.4% of total DOTs. Seventy-two of 86 (83.7%) patients received 620 intravenous DOTs; of these, 79 (12.7%) IV DOTS were unnecessary.

Conclusions

We have identified excess antibiotic prescribing in General surgery with comparable excess DOTs at all three time-points.
P05 Safety, tolerability, and immunogenicity of V114 compared with PCV13 in preterm infants: a pooled subgroup analysis of four Phase III studies
Authors: Banniettis Natalie , Chapman Timothy J , Xu Shengjie , Lupinacci Robert , Shi Yaru , Shekar Tulin , Flores Sheryl A , Feemster Kristen , Yi Jumi , McFetridge Richard , Kaminski Janusz , Bickham Kara , Buchwald Ulrike , Musey Luwy
Published: January 2023

Background

Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants, mainly due to underlying comorbidities and immunological immaturity. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in 13-valent PCV (PCV13) plus two additional serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (<37 weeks gestational age) enrolled in 4 paediatric Phase III studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13.

Methods

Safety was evaluated as the proportion of participants with AEs following each vaccination. Serotype-specific anti-pneumococcal IgG GMCs, IgG response rates, and OPA GMTs were measured at 30 days post-primary series (PPS; post-dose 3 [PD3]), pre-toddler dose, and 30 days post-toddler dose (PTD; post-dose 4 [PD4]).

Results

174 and 180 participants received V114 and PCV13, respectively. Mean gestational age was 35.4 weeks (range: 27–37 weeks). Proportions of participants with any AE were comparable between vaccination groups following each vaccination; most solicited AEs were transient (≤3 days) and of mild-to-moderate intensity. V114-elicited IgG GMCs (Figure 1), IgG response rates, and OPA GMTs were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days PPS (PD3) and PTD (PD4).

Conclusions

In preterm infants, vaccination with V114 has an acceptable safety profile, is well tolerated, and induces comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to V114 serotypes 22F and 33F. Study results support use of V114 in preterm infants.
P06 The 15-valent pneumococcal conjugate vaccine (PCV) V114 induces cross-reactive antibodies against pneumococcal serotype 6C
Authors: Shi Yaru , Nolan Katrina , Burton Robert L , Murphy Rocio , Banniettis Natalie , Musey Luwy , Buchwald Ulrike
Published: January 2023

Background

Pneumococcal serotype 6C has structural similarity with serotype 6A and, to a lesser degree, serotype 6B. The 13-valent PCV (PCV13), which contains serotypes 6A and 6B, induces cross-reactive opsonophagocytic killing activity (OPA) antibodies to serotype 6C, with an observed decline in 6C disease incidence. V114 is a 15-valent PCV containing the 13 serotypes in PCV13 and two unique serotypes (22F and 33F). This study evaluated whether V114 elicits cross-reactive OPA antibodies to serotype 6C.

Methods

OPA antibodies to serotypes 6A, 6B, and 6C were evaluated in serum samples taken pre-vaccination and 30 days post-vaccination (single dose) from adults ≥50 years of age, and 30 days pre- and post-dose 4 from toddlers 12–15 months of age at fourth dose, who received V114 or PCV13 in the adult and paediatric V114 phase II proof-of-concept studies, respectively. The degree of inhibition of OPA antibody activity for serotypes 6A, 6B, and 6C after adsorption with serogroup 6 polysaccharides was evaluated in adult samples.

Results

Samples from 250 adults (V114, n=150; PCV13, n=100) and 150 paediatric participants (V114, n=100; PCV13, n=50) were included. In both the adult and paediatric populations, observed OPA geometric mean titres (GMTs) to serotypes 6A, 6B, and 6C were comparable across vaccination groups; however, the cross-reactive response to serotype 6C was stronger in infants than adults. The inhibition analysis demonstrated the specificity of antibody responses.

Conclusions

V114 induces cross-reactive antibodies to serotype 6C in adult and paediatric populations that are specific and comparable to those induced by PCV13.
P08 A Phase 1, randomized, double-blind study to evaluate the safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine (PCV) (V116) in adults
Authors: Platt Heather , Fernsler Doreen , Gallagher Nancy , Sapre Aditi , Polis Adam , Hall Lori , Tamms Gretchen , Schwartz Howard , Skinner Julie , Joyce Joseph , Murphy Rocio , Musey Luwy
Published: January 2023

Background

V116, an investigational 21-valent PCV, contains the following pneumococcal polysaccharides (PnPs): 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B, and a de-O-acetylated 15B (deOAc15B). This phase 1 study evaluated the safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-naive adults compared with the 23-valent polysaccharide pneumococcal vaccine (PPSV23).

Methods

Adults (n=90) 18–49 years were randomized 1:1:1 to receive a single dose of V116-1 (2 μg dose/each PnPS, V116-2 (4 μg dose/PnPS) or PPSV23. Adverse events (AEs) were collected following vaccination. Pneumococcal serotype-specific opsonophagocytic activity (OPA) was measured prior to and 30 days postvaccination (Day 30).

Results

There were no serious AEs, deaths, or discontinuations due to AEs. Immune responses at Day 30 in the V116-1 and V116-2 groups were generally comparable to PPSV23 for the common serotypes and higher than PPSV23 for the unique serotypes. At Day 30, the OPA GMTs were higher in the V116-2 group compared with the V116-1 group for all serotypes except 9N. The OPA geometric mean titre ratio (95% CI) (V116-2/PPSV23) ranged from 0.89 (0.58, 3.51) to 2.40 (1.24, 4.62) for all common serotypes and 2.80 (1.64, 4.79) to 58.07 (25.10, 134.33) for all unique serotypes; the lower bound of the 95% CI for the OPA GMT ratio (V116-2/PPSV23) was >0.5 for all common serotypes and >1.0 for all unique serotypes.

Conclusions

These safety and immunogenicity data support the continued development of V116 for the prevention of pneumococcal disease in adults.
P09 A Phase 2, randomized, double-blind study to evaluate the safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine (V116) in adults ≥50 years
Authors: Omole Tosin , Cardona Jose , Fraser Neil J , Pagnussat Sandra , Mularski Richard , Andrews Charles , Daboul Nizar , Sapre Aditi , Li Jianing , Fernsler Doreen , Xu Weifeng , Gallagher Nancy , Hall Lori , Platt Heather
Published: January 2023

Background

V116 is an investigational 21-valent PCV containing the following pneumococcal polysaccharides: 3, 6A, 7F, 8, 9N, 10A, 11A,12F, 15A, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B, and a de-O-acetylated 15B (deOAc15B). This phase 2 study evaluated the safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-naïve adults compared with a 23-valent pneumococcal vaccine (PPSV23).

Methods

Adults (n=508) ≥50 years were randomized 1:1 and received a single dose of V116 or PPSV23; randomization was stratified by age (50–64 years, 65–74 years, and ≥75 years). Adverse events (AEs) were collected following vaccination. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG were measured before and 30 days after vaccination (Day 30). Primary immunogenicity objectives were to assess the noninferiority of V116 to PPSV23 for the shared serotypes and the superiority of V116 to PPSV23 for the unique serotypes.

Results

There were no vaccine-related serious AEs or vaccine-related deaths. V116 met noninferiority criteria compared with PPSV23 for all shared serotypes [based on the lower bound of the 95% CIs for the estimated OPA GMT ratios (V116/PPSV23) being >0.33 at Day 30] and met superiority criteria for the unique serotypes [based on the lower bound of the 95% CIs for the estimated OPA GMT ratios (V116/PPSV23) being >1.0 at Day 30].

Conclusions

In adults ≥50 years, V116 is well tolerated with a safety profile comparable to PPSV23, elicits an immune response that is noninferior to PPSV23 for the shared serotypes and superior to PPSV23 for the unique serotypes.
P12 Commissioning for Quality and Innovation (CQUIN) schemes—revisiting urinary tract infection (UTI) management. What worked? What lasted? What next?
Authors: Slatter Mandy , Aprilia Valentin , Boyd Rebecca , Chan Teresa
Published: January 2023

Background

UK CQUIN schemes encourage an improvement focus on a specific area of care. In 2019, CQUIN CCG1a: Improving the management of lower UTI in older people1 was adopted at the RUH resulting in increased alignment with UK guidance on diagnosis and treatment.2 Our aim was to investigate whether this improvement was sustained two years later. This would help inform quality improvement interventions prior to adoption of the 2022 CQUIN, CCG2: Appropriate antibiotic prescribing for UTI in adults aged 16+.3

Objectives

Service evaluation of the UTI pathway including compliance with two of the CQUIN care processes for UTI diagnosis in patients age 65+ presenting to ED (not admitted): (i) diagnosis excludes use of urine dipstick in people aged 65+; and (ii) urine sample sent to microbiology as per UK guidance.2

Methods

A search of the electronic patient record for key terms (Table 1) identified 6076 ED attendances for patients age 65+ between 1 August and 31 October 2021 of which 40 were identified with a primary diagnosis of UTI not requiring hospital admission. Paramedic, ED and Urgent Treatment Centre notes (paper and electronic) were reviewed in detail and information gathered regarding presence/absence of UTI symptoms aligned to diagnostic guidelines;2 presence/absence of urine dipstick test; and presence/absence of urine sample for culture and susceptibility testing. Findings were compared with identical trust data for patients (admitted and non-admitted) obtained during the 2019 CQUIN: Q1 April–June; Q2 July–September; Q3 October–December. During this period improvement interventions were implemented.

Results

See Table 2.

Conclusions

Following intensive staff education improved practice regarding urine dipstick testing and appropriate urine sampling in elderly patients with possible UTI was observed during the 2019 CQUIN period. Two years later this improvement had not been sustained. When planning interventions during the 2022 CQUIN,3 consideration should be given to a bundle of interventions including education, data feedback and systems improvement, for example, computerized decision support systems (CDSS) to embed sustained change.
P19 Antibacterial susceptibility patterns and resistance genes from bacterial isolates of neonatal sepsis
Authors: Aziegbemhin Abumhere S , Enabulele Onaiwu I , Oviasogie Faith E , Omo-Omorodion Blessing I , Okonkwo Ikechukwu R
Published: January 2023

Background

Neonatal sepsis is a bloodstream infection of neonates. It affects newborns globally, particularly in developing countries. Mothers carrying bacterial pathogens may transmit them to their neonates. Poor or inadequate diagnosis often leads to complications with attendant high morbidity and mortality. The need for prompt detection, diagnosis as well as effective treatment monitoring of antibacterial resistant strains is of utmost priority.

Methods

A total of 100 mother-neonate dyad consisting of 90 pairs (with term, preterm or post-term babies) with clinical features of sepsis admitted at the Neonatal Units of Stella Obasanjo Hospital, Central Hospital and University of Benin Teaching Hospital, Benin City and 10 putative controls consisting of apparently healthy neonates were recruited for this study. Bacterial isolation, characterization and identification were carried out using standard microbiology techniques. Antibiotics resistance of bacterial isolates to the routinely used antibacterial agents ampicillin/sulbactam (Unasyn, UN), cefuroxime (CXM), ceftazidime (CTX) and azithromycin (AZM) in neonatal units in this locale was determined using the disc diffusion (Kirby–Bauer) method. Plasmid curing was carried out by inoculating bacteria in 0.1 mL acridine orange. Based on their resistance patterns and curing reaction, one representative bacterial isolates (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus sciuri and Bacillus cereus) each from saliva, blood and genital swab from five mother-neonate dyad were screened for virulence genes. Antibacterial resistance genes screened for are mecA, mph(A) or blaIMP.

Results

Bacterial isolates showed varying resistance to all antibacterial agents used. Over fifty percent (50%) of the bacterial isolates exhibited MDR phenotype. Unasyn (UN) had more activity agent bacterial isolates. However, resistance to cefuroxime (CXM), ceftazidime (CTX) and azithromycin (AZM) was common. Furthermore, plasmid curing revealed that bacterial isolates harboured resistance plasmid. None of the bacterial isolates were completely cured of their resistant markers. Plasmid-borne antibiotic-resistance markers identified include CTX,UN; CTX,AZM: CXM,AZM; and UN,AZM. Representative bacterial isolates harboured either mecA mph(A) or blaIMP genes.

Conclusions

There is the possibility of transmission of antibacterial resistance genes from bacterial isolates in mothers as well as neonatal intensive care units to neonates thus negatively affecting outcomes of neonatal sepsis and further proliferation of antibacterial resistant strains. Responsible use of antibacterial in this locale is advocated.
Study on the hepatotoxicity and potential mechanism of gefitinib based on CYP450 in mice and AML12 cells
Authors: Yin Xiaoting , Ma Suzhen , Li Mengyuan , Lu Shuaifei , Zhang Changjing , Liu Hui , Li Caiyin , Su Pan , Bai Ming , Li Yucheng
Published: January 2023

Objectives

Gefitinib is mainly used for the treatment of non-small-cell lung cancer. Hepatotoxicity is one of the main side effects of gefitinib, and seriously affects the treatment process of the disease. However, the hepatotoxicity mechanism of gefitinib remains unclear.

Methods

The hepatotoxicity of different doses of gefitinib was investigated in mice and AML-12 cells, and the possible correlation of hepatotoxicity with CYP450 was analysed.

Key findings

The toxic effects of gefitinib were confirmed by the increased liver index, decreased body weight and survival rate, injured liver function and histopathology followed 16 days of oral administration. Gefitinib (400 mg/kg) upregulated the hepatic mRNA expression of CYP1A1 and downregulated the CYP2D9 and CYP2D10 in mice. Furthermore, we verified that gefitinib produced cytotoxicity on AML-12 cells in a dose and time-dependent manner, and confirmed that gefitinib (20 μM) induced cell apoptosis, upregulated mRNA expression of CYP1A1 and downregulated CYP2D9 and CYP2D10. Pearson correlation analysis also showed that the hepatotoxicity of gefitinib was positively correlated with CYP1A1 and negatively correlated with CYP2D9 and CYP2D10.

Conclusions

Our results suggested that the hepatotoxicity gefitinib may be associated with CYP1A1, CYP2D9 and CYP2D10. These findings will contribute to a better understanding of the mechanism of gefitinib hepatotoxicity.
Nutcracker phenomenon secondary to superior mesenteric artery syndrome
Authors: Pacheco Tulio Brasileiro Silva , Chacon Andre Camara Matoso , Brite Jasmine , Sohail Amir H , Gangwani Manesh Kumar , Malgor Rafael D , Levine Jun , Amaral Gurgel Gutenberg do
Published: January 2023

Superior mesenteric artery (SMA) syndrome, compression of the duodenum due to a decreased angle between the aorta and SMA, has a wide range of clinical presentations making it difficult to diagnose. Compression of the left renal vein is known as Nutcracker syndrome. We present the case of a 26-year-old male with a delayed diagnosis of SMA syndrome and Nutcracker phenomenon due to the patient’s history of chronic pancreatitis. As a result of his obstruction and aspiration pneumonia, he was diagnosed with septic shock. The patient was treated for septic shock and maintained on an enteric diet with improvement in the body mass index and complete resolution of SMA syndrome symptoms.
An extremely rare complication of intestinal stoma formation: parastomal evisceration 1-year post-loop ileostomy
Authors: Edwards Murphy Amy , Stakelum Aine , Razzak Saad , Ashraf Jawad , Awan Faisal
Published: January 2023

Intestinal stoma formation is an important and frequently performed procedure in emergency and elective general surgery. Parastomal evisceration is an extremely rare complication of stoma formation. The literature to date consists of a small number of case reports only. We report the case of a 54-year-old patient who presented 1-year post-loop ileostomy formation with a large parastomal evisceration. This was managed with emergency laparotomy. Our case highlights the high morbidity of this rare complication and the importance of emergent management and patient’s education.
Salutary attributes of probiotic human gut lactobacilli for gut health
Authors: Idicula Dona V , R Krishnaprasad , Parappilly Sherin Joy , Joy Neya , Balan Jithasha , George Sumi Mary
Published: January 2023

Lactobacilli are GRAS organisms and are important members of gut microbiota. They have been strongly recommended as probiotics because of many benefits provided by them to overall human health. Human gut lactobacilli with salutary properties can provide additional advantages. Limosilactobacillus fermentumL1 MW600457, L. fermentumL3 MW600480, L. fermentumL4 MW600464, L. fermentumL5 MW600493, L. fermentumL6 MW600495, L. fermentumL7 MW600496, L. fermentumL8 MW485761, Lactiplantibacillus plantarumL9 MW485746, and Ligilactobacillus salivariusL10 MW600498 with in vitro probiotic properties were explored for salutogenic characteristics. Salutary properties like β-galactosidase activity, anthelminthic property assay, anti-inflammatory assay, antidiabetic study, cholesterol assimilation assay, and biofilm assay were performed. All the isolates were positive for β-galactosidase activity. The anthelminthic property with minimum paralysis time and death time between 16–25 min was shown by L.fermentumL8 MW485761. Anti-inflammatory activity with bovine serum albumin was maximum at 200 μg ml−1 concentration. α-amylase inhibitory activity was maximum for L. fermentumL8 MW485761 (51%). Maximum cholesterol assimilation was reported for L. fermentumL6 MW600495 (76%). Strong biofilm forming ability for all isolates improved the colonization and stability as probiotics. Human gut lactobacilli with salutary properties can make an efficient probiotic.
A Mixed Methods Investigation on the Relationship Between Perceived Self-Regard, Self-Efficacy, and Commitment to Serve Among Military Medical Students
Authors: Nevins Natalie A , Singer-Chang Gail , Dailey Stephanie F , Roche Rosellen , Dong Fanglong , Peters Sara N , Thompson Trevor , Ryznar Rebecca , LaPorta Anthony
Published: January 2023

Introduction

Routinely faced with potentially traumatizing situations, resilience is critical for military physicians. However, related studies are limited in scope. The current study distinctively combines hyper-realistic immersion training for military medical students with emotional intelligence and hardiness measures. With self-reflection shown to improve performance, qualitative inquiry was concurrently conducted in a mixed methodology approach to provide a uniquely comprehensive perspective on the resilience training needs of this population.

Materials and Methods

Thirty-four osteopathic military medical students participated in a week-long training simulating real-life combat and mass casualty events. The Emotional Quotient-Inventory 2.0 (EQ-i 2.0) and Hardiness Resilience Gauge were administered as pre- and post-test measures. Paired t-tests were used to determine statistically significant gains, and a multiple case study analysis of a six-student focus group allowed for the synchronization of quantitative and qualitative data. Institutional Review Board approval for the study was obtained through Rocky Vista University with a reciprocal agreement with Touro University California’s Institutional Review Board. All students participating in the study received written informed consent.

Results

Qualitative findings for this study aligned with this current year’s findings of statistically significant results in the improvement of the Overall EQ-i and Overall Hardiness. Qualitative responses thematically analyzed demonstrated environmental realism, adaptation, increased awareness, and positive interpersonal and clinical outlook. Notable increases occurred in all EQ-i domains except Decision-Making and Stress Tolerance. The Self-Perception domain saw significant increases in Self-Regard and Emotional Self-Awareness while Well-Being and Optimism simultaneously improved.

Conclusion

This unique pilot study showed that quantitative and qualitative results aligned, supporting the finding that a safe trauma-related training environment can improve the confidence and resilience in military medical students. The goal of this training was to promote resilience and mitigate trauma. Results demonstrate improved self-efficacy and enhanced commitment. Increases in self-awareness and confidence made participants more inclined to see their worth and strengthened their sense of duty as described in their qualitative responses. Pervasive gains suggest that the training aligned well with its purpose, and the methods employed enhanced participant experience. Long-term follow-up studies are needed to assess outcome sustainability.
Parametric instability in warped astrophysical discs: growth, saturation, and feedback
Authors: Fairbairn Callum W , Ogilvie Gordon I
Published: January 2023

Attempts to understand the dynamics of warped astrophysical discs have garnered significant attention, largely motivated by the growing catalogue of observed distorted systems. Previous studies have shown that the evolution of the warp is crucially regulated by the internal flow fields established by the undulating geometry. These are typically modelled as laminar horizontal, shearing flows which oscillate back and forth at approximately the orbital frequency. However this shearing motion is known to be susceptible to a hydrodynamic, parametric instability of inertial waves which might modify the warped dynamics. Whilst the linear growth phase is well understood, the subsequent non-linear saturation combined with the self-consistent feedback onto the warp has not been studied. In this work, we implement a novel numerical setup using the recent ring model framework of Fairbairn and Ogilvie, within the Lagrangian code gizmo. We formally identify several locally growing modes in the simulation, as predicted by a three-mode coupling analysis of the instability, and find decent agreement with the theoretical growth rates. We understand the saturation mechanism as a wave breaking process which suppresses the growth of shorter wavelength parametric couplings first, whilst allowing the longest mode to dominate the final quasi-steady, wave-like turbulence. The Reynolds stresses, transporting energy from the warp to the small scales, can be effectively modelled using a time-dependent, anisotropic viscous alpha model which closely captures the amplitude and phase evolution of the warp. Consequently, this model might help inform future global studies which are commonplace but typically do not resolve the parametric instability.
How Many Sirtuin Genes Are Out There? Evolution of Sirtuin Genes in Vertebrates With a Description of a New Family Member
Authors: Opazo Juan C , Vandewege Michael W , Hoffmann Federico G , Zavala Kattina , Meléndez Catalina , Luchsinger Charlotte , Cavieres Viviana A , Vargas-Chacoff Luis , Morera Francisco J , Burgos Patricia V , Tapia-Rojas Cheril , Mardones Gonzalo A
Published: January 2023

Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.