bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract

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

Abstract

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 (&lt;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

Abstract

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

Abstract

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 &gt;0.5 for all common serotypes and &gt;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

Abstract

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 &gt;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 &gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract
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.