bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features
Authors: Liu Zhigang , Xin Baozhong , Smith Iris N , Sency Valerie , Szekely Julia , Alkelai Anna , Shuldiner Alan , Efthymiou Stephanie , Rajabi Farrah , Coury Stephanie , Brownstein Catherine A , Rudnik-Schöneborn Sabine , Bruel Ange-Line , Thevenon Julien , Zeidler Shimriet , Jayakar Parul , Schmidt Axel , Cremer Kirsten , Engels Hartmut , Peters Sophia O , Zaki Maha S , Duan Ruizhi , Zhu Changlian , Xu Yiran , Gao Chao , Sepulveda-Morales Tania , Maroofian Reza , Alkhawaja Issam A , Khawaja Mariam , Alhalasah Hunaida , Houlden Henry , Madden Jill A , Turchetti Valentina , Marafi Dana , Agrawal Pankaj B , Schatz Ulrich , Rotenberg Ari , Rotenberg Joshua , Mancini Grazia M S , Bakhtiari Somayeh , Kruer Michael , Thiffault Isabelle , Hirsch Steffen , Hempel Maja , Stühn Lara G , Haack Tobias B , Posey Jennifer E , Lupski James R , Lee Hyunpil , Sarn Nicholas B , Eng Charis , Gonzaga-Jauregui Claudia , Zhang Bin , Wang Heng 
Published: August 2023

AbstractProtein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.
Telomere-to-telomere haplotype-resolved reference genome reveals subgenome divergence and disease resistance in triploid Cavendish banana
Authors: Huang Hui-Run , Liu Xin , Arshad Rida , Wang Xu , Li Wei-Ming , Zhou Yongfeng , Ge Xue-Jun 
Published: August 2023

Abstract
Banana is one of the most important crops of the world. Cavendish-type bananas, which have a monospecific Musa acuminata origin (AAA), account for around half of the global banana production, thereby are of great significance for human societies. However, until now, the high-quality haplotype-resolved reference genome was still undecoded for banana cultivars. Here, we reported the telomere-to-telomere (T2T) and haplotype-resolved reference genome of ‘Baxijiao’ (Cavendish) consisting of three haploid assemblies. The sizes of the three haploid assemblies were estimated to be 477.16 Mb, 477.18 Mb, and 469.57 Mb, respectively. Although with monospecific origins, the three haploid assemblies showed great differences with low levels of sequence collinearity. Several large reciprocal translocations were identified among chromosomes 1, 4, and 7. An expansion of gene families that might affect fruit quality and aroma was detected, such as those belonging to sucrose/disaccharide/oligosaccharide catabolic processes, sucrose metabolic process, starch metabolic process, and aromatic compound biosynthetic process. Besides, an expansion of gene families related to anther and pollen development was observed, which could be associated with parthenocarpy and sterility of the Cavendish cultivar. Finally, much fewer resistance genes were identified in ‘Baxijiao’ than in M. acuminata, particularly in the gene clusters in chromosomes 3 and 10, providing potential targets to explore for molecular analysis of disease resistance in banana. This T2T haplotype-resolved reference genome will thus be a valuable genetic resource for biological studies, molecular breeding, and genetic improvement of banana.
Identification and profile of phenolamides with anthracnose resistance potential in tea (Camellia sinensis)
Authors: Wang Wenzhao , Xie Xingcui , Lv Yuanyuan , Guan Haonan , Liu Lu , Huang Qian , Bao Yumeng , Zhou Jie , Bao Lu , Gong Chunmei , Yu Youben 
Published: August 2023

Abstract
Tea anthracnose is a prevalent disease in China that can lead to reduced tea production and lower quality, yet there is currently a lack of effective means for controlling this disease. In this study, we identified 46 phenolamides (including 27 isomers) in different tissues and organs of tea plants based on a developed workflow, and the secondary mass spectra of all these compounds have been documented. It was revealed that tea plants predominantly accumulate protonated aliphatic phenolamides, rather than aromatic phenolamides. The profile of phenolamides indicate that their buildup in tea plants is specific to certain tissues and acyl-acceptors, and this distribution is associated with the extent of phenolamide acyl-modification. Additionally, it was observed that N-Feruloylputrescine (Fer-Put, a type of phenolamides) was responsive to the stimulated accumulation of the tea anthracnose pathogen. The findings of anti-anthracnose experiments in vitro and on tea leaf demonstrated that Fer-Put was capable of significantly inhibiting the growth of anthracnose pathogen colony, effectively prevented tea leaf disease. Furthermore, it was observed that Fer-Put treatment can enhance the antioxidant enzyme activity of tea leaves. TEA002780.1 and TEA013165.1 gene may be responsible for the biosynthesis of Fer-Put in the disease resistance process in tea plants. Through these studies, the types and distribution of phenolamides in tea plants have been elucidated, and Fer-Put's ability to resist anthracnose has been established, providing new insights into the resistance of tea anthracnose.
Developing a highly efficient CGBE base editor in watermelon
Authors: Wang Dong , Chen Yani , Zhu Tao , Wang Jie , Liu Man , Tian Shujuan , Wang Jiafa , Yuan Li 
Published: August 2023

Abstract
Cytosine and adenosine base editors (CBEs and ABEs) are novel genome-editing tools that have been widely utilized in molecular breeding to precisely modify single-nucleotide polymorphisms (SNPs) critical for plant agronomic traits and species evolution. However, conventional BE editors are limited to achieve C-to-T and A-to-G substitutions, respectively. To enhance the applicability of base editing technology in watermelon, we developed an efficient CGBE editor (SCGBE2.0) by removing the uracil glycosylase inhibitor (UGI) unit from the commonly used hA3A-CBE and incorporating the uracil-DNA glycosylase (UNG) component. Seven specific guide RNAs (sgRNAs) targeting five watermelon genes were designed to assess the editing efficiency of SCGBE. The results obtained from stably transformed watermelon plants demonstrated that SCGBE2.0 could efficiently induce C-to-G mutations at positions C5–C9 in 43.2% transgenic plants (with a maximum base conversion efficiency of 46.1%) and C-to-A mutation at position C4 in 23.5% transgenic plants (with a maximum base conversion efficiency of 45.9%). These findings highlight the capability of our integrated SCGBE2.0 editor to achieve C-to-G/A mutations in a site-preferred manner, thus providing an efficient base editing tool for precise base modification and site-directed saturated mutagenesis in watermelon.
Healthy live birth following embryo transfer of a blastocyst of tetrapronuclear (4PN) origin: a case report
Authors: Bredbacka Peter , Capalbo Antonio , Kananen Kirsi , Picchetta Ludovica , Tomás Candido 
Published: August 2023

Abstract
During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronuclei, one arising from the oocyte and the other from the male gamete. Embryos derived from zygotes with a pronuclei number other than two are assumed to possess a ploidy abnormality and their transfer is usually avoided owing to increased risk of implantation failure, miscarriage, and molar pregnancies. Nonetheless, the inclusion of genotyping data in preimplantation genetic testing has revealed that a normal diploid configuration is possible in embryos deriving from zygotes with an abnormal pronuclei number such as tripronuclear and one pronucleus. Here, we present a one-of-a-kind transfer of a tetrapronuclear-derived embryo that was discovered to be diploid and negative for other whole chromosome or segmental aneuploidies during preimplantation genetic testing using a targeted next-generation sequencing approach. The transfer resulted in the live birth of a healthy infant who is now 4 years old and has no apparent health or developmental impairments.
Single fathers’ experiences of using egg donation and surrogacy to start a family
Authors: Jones C , Jadva V , Zadeh S , Golombok S 
Published: August 2023

Abstract

STUDY QUESTION
What are the experiences of single men using egg donation and surrogacy as a route to parenthood?

SUMMARY ANSWER
The fathers mainly had a positive relationship with the surrogate and simultaneously exercised agency, and experienced challenges, during the process of surrogacy.

WHAT IS KNOWN ALREADY
Little is known about single men’s experiences of egg donation and surrogacy arrangements. Studies have focused on single men’s decision-making processes about the use of surrogacy and family functioning once these families are formed. Questions remain about how fathers experience and navigate the process of surrogacy as a single man.

STUDY DESIGN, SIZE, DURATION
The study is an international, in-depth qualitative study of fathers who chose to begin a family and parent alone. Data were collected between 2018 and 2021 as part of a larger study of solo fathers with different routes to parenthood. The present study reports on 21 fathers who used surrogacy and egg donation to begin their family. The average age of the fathers was 44 years, the fathers had young children aged 6 years or younger, and lived in countries across Australia, Europe, and North America.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Purposive sampling was used to recruit participants. In-depth semi-structured interviews were conducted. Interview topics included fathers’ experiences of the process of using egg donation and surrogacy, and navigating the relationship with the surrogate. The audio-recorded interviews lasted around 2 hours and were subsequently transcribed verbatim.

MAIN RESULTS AND THE ROLE OF CHANCE
Data were analysed using reflexive thematic analysis and qualitative content analysis. Most of the fathers chose an identifiable egg donor. Regarding the relationship with the surrogate, many fathers had remained in contact with her, but to differing degrees, and they generally reported positive relationships. Thematic analysis led to the identification of three themes relating to the fathers’ experiences of choosing surrogacy as a single man: the ability to make choices; challenges and constraints; and special relationship.

LIMITATIONS, REASONS FOR CAUTION
Due to the variation between different countries regarding laws on surrogacy, contextual factors may have impacted on the experiences of single fathers, and the sample size was small. However, the research provides new insights into an area with little academic literature.

WIDER IMPLICATIONS OF THE FINDINGS
Given the growing trend of single men having children through surrogacy, the findings suggest that this new path to parenthood can be both rewarding and challenging. Single men may benefit from tailored support and counselling to help them navigate the surrogacy journey.

STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the Wellcome Trust (grant number 208013/Z/17/Z). The authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER
n/a
Stroke Following Coronavirus Disease 2019 Vaccination: Evidence Based on Different Designs of Real-World Studies
Authors: Liu Junyu , Cao Fang , Luo Chun , Guo Yuxin , Yan Junxia 
Published: August 2023

Abstract

Background
We aimed to evaluate whether coronavirus disease 2019 (COVID-19) vaccination was associated with stroke.

Methods
We conducted a systematic meta-analysis of studies using cohort, self-controlled case series (SCCS), and case-crossover study (CCOS) designs to evaluate incidence risk ratios (IRRs) and 95% confidence intervals (CIs) of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination. Risks of stroke were pooled among subpopulations categorized by vaccine type, dose, age, and sex. Sensitivity analysis was performed by different defined risk periods.

Results
Fourteen studies involving 79 918 904 individuals were included. Cohort studies showed decreased risks of IS (IRR, 0.82 [95% CI, .75–.90]) and HS (IRR, 0.75 [95% CI, .67–.85]) postvaccination, but not CVST (IRR, 1.18 [95% CI, .70–1.98]). SCCS identified increased risks 1–21 days postvaccination (IRRIS, 1.05 [95% CI, 1.00–1.10]; IRRHS, 1.16 [95% CI, 1.06–1.26]) or 1–28 days postvaccination (IRRIS, 1.04 [95% CI, 1.00–1.08]; IRRHS, 1.37 [95% CI, 1.15–1.64]), similar to CVST (IRR, 1.58 [95% CI, 1.08–2.32]). CCOS reported an increased risk of CVST after ChAdOx1 vaccination (IRR, 2.9 [95% CI, 1.1–7.2]).

Conclusions
Although different study designs yielded inconsistent findings, considering the relatively low background incidence of stroke and benefits of vaccination, even a potentially increased risk of stroke postvaccination should not justify vaccine hesitancy.
The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence
Authors: Barker Charlotte I S , Kipper Karin , Lonsdale Dagan O , Wright Kirstie , Thompson Georgina , Kim Min , Turner Mark A , Johnston Atholl , Sharland Mike , Standing Joseph F 
Published: August 2023

Abstract

Background
Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.

Objectives
The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.

Methods
NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval.

Results
For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT&gt;MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h−1 and 1.3 h−1) and bioavailability terms (62.7% and 58.7%, respectively).

Conclusions
NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.
P02 Strategies for Older People living in care homes to prevent Urinary Tract Infection: the ‘StOP UTI’ realist synthesis of evidence
Authors: Prieto Jacqui , Wilson Jennie , Tingle Alison , Cooper Emily , Handley Melanie , Rycroft-Malone Jo , Bostock Jennifer , Loveday Heather 
Published: August 2023

Abstract

Background
Urinary tract infection (UTI) is the most diagnosed infection in older people living in care homes, accounting for more than 50% of antibiotic prescriptions in this setting. Older people often present with non-specific or atypical symptoms, which may have other origins and are difficult for care home staff to interpret.

Objectives
To identify interventions that could be effective for preventing and recognizing UTI in older people living in care homes in the UK and explore the mechanisms by which they work, for whom and under what circumstances.

Methods
A synthesis of evidence using a realist approach was undertaken to develop, test and refine programme theories, which are the units of analysis within the realist approach. These were expressed as context + mechanism=outcome configurations (CMOc). Their practical relevance and potential for implementation was established through consultation with stakeholders and teacher-learner interviews.

Results
We identified nine CMOc, which describe what needs to happen in care homes to facilitate improvement in practice for the prevention and recognition of UTI. These were arranged under three theory areas: (i) supporting accurate recognition of UTI; (ii) preventing UTI and catheter-associated UTI; and (iii) the infrastructure and systems required to make best practice happen. Our programme theories draw on evidence from a range of areas including infection prevention and control, antimicrobial stewardship, leadership and safety culture in care homes and person-centred care. The findings suggest a whole care team approach, involving residents, their family carers, care home staff and visiting health professionals is needed to develop and implement strategies to improve UTI prevention and recognition. Support at system level, with regulatory and inspection frameworks aligned to evidence on prevention and recognition of UTI, is imperative to ensure the resources and infrastructure are available to enable care home managers and their staff to prioritize this as part of person-centred care.

Conclusions
Our findings have identified the active components of strategies that are effective in preventing and recognizing UTI in older people living in care homes and will help guide delivery of future improvement programmes and research.
P03 Effects of a dietary supplement containing probiotics, cinnamon and cranberry extracts in the prevention of recurrent cystitis
Authors: Ait Abdellah S , Dauchet Q , Leblanc A , Bohbot J M 
Published: August 2023

Abstract

Objectives
A study was conducted to evaluate the effects of a dietary supplement containing two probiotic strains (Lactobacillus helveticus LA201 and Lactobacillus plantarum BL3706, 5×109 cfu per two tablets) and extracts of cinnamon (320 mg) and cranberry (100 mg) in the prevention of recurrent cystitis.

Methods
A total of 80 women (18–65 years) were included who reported at least two episodes of cystitis in the past 6 months, at least one of which was a bacterial cystitis confirmed by a urine cytobacteriological examination or a physician, and for whom the episodes of cystitis had a strong impact on their quality of life (QoL; Acute Cystitis Symptom Score [ACSS] QoL questionnaire &gt;2). Participants took two tablets of the supplement per day for 6 months (n=37; Group 1) or no supplement (n=38; Group 2). The ACSS questionnaire was completed every 15 days, or in case of cystitis, for 8 months (total score ranged from 0 [no urinary discomfort] to 39 [maximum discomfort]). The two groups were comparable at baseline, with a higher proportion of postmenopausal women in Group 1.

Results
During the 6 months, 2/3 of the women in Group 1 had no recurrence of cystitis (0 symptomatic cystitis episodes [SCE]) while 2/3 of the women in Group 2 had at least one SCE (P=0.03 Fisher test). The total ACSS score during SCE was significantly lower in Group 1 (8.4±5.1 versus 12±5.9, P&lt;0.0001 ANOVA), with results in favour of Group 1 for dimensions assessing typical symptoms of acute cystitis and QoL. Compliance and tolerance were excellent.

Conclusions
These results suggest that the supplement may help prevent recurrence of cystitis, particularly in postmenopausal women who are at high risk.
P05 Comparing patients’ and healthcare professionals’ experiences and views on the management of recurrent urinary tract infections: qualitative evidence synthesis and meta-ethnography
Authors: Sanyaolu Leigh , Hayes Catherine , Lecky Donna , Weightman Alison , Ahmed Harry , Cannings-John Rebecca , Edwards Adrian , Wood Fiona 
Published: August 2023

Abstract

Background
Urinary tract infections (UTIs) are common and result in significant morbidity, negative impacts on daily life, reduced quality of life and reduced work attendance. Recurrence is common and recurrent UTIs have an estimated annual prevalence of 3%. The experience of women with recurrent UTIs is not well understood and how this compares to the views of healthcare professionals (HCPs) is unknown.

Objectives
This qualitative evidence synthesis aims to understand the experiences of women with recurrent UTIs and compare them to primary care HCPs.

Methods
We systematically searched MEDLINE, Embase, CINAHL, PsychInfo, ASSIA, Web of Science and the grey literature from inception to June 2022 for primary qualitative studies. Meta-ethnography was conducted to synthesize the studies and the findings for women with recurrent UTIs and HCPs were then compared.

Results
Twelve primary qualitative studies published from 2005 to 2022 and conducted in Europe and the USA were included. Two studies involved primary care staff; nine studies involved women with experience of recurrent UTIs. One study involved both. Patients and HCPs had similar views in terms of the causes of recurrent UTIs and self-management and similar concerns about an underlying cause and antibiotic use. They also had similar views on the impact of recurrent UTIs, however patients felt HCPs did not appreciate the impact of recurrent UTIs. There were conflicts in terms of the expectation for antibiotics and the need for further investigation and referral.

Conclusions
This is the first qualitative evidence synthesis on the experiences of women with recurrent UTIs and the views of primary care HCPs. It demonstrates that women with recurrent UTIs and HCPs share several similar views and concerns but there were significant communication gaps. Further guidance development and a patient decision aid could help address these gaps.