bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective study on health-related quality of life, oral mucositis and oral health on during treatment of head and neck cancer
Authors: Karlsson Charlott , Bohm Niklas , Andersson Jessica Skoogh , Finizia Caterina , Almståhl Annica 
Published: June 2024

Abstract
Background
Few studies have examined health related Quality of Life (HR-QoL) during the treatment of head and neck cancer (HNC) with even fewer focusing on the impact of oral mucositis (OM) on HR-QoL. Studies performed during treatment of HNC makes it possible to follow fluctuations in HR-QoL, OM and other treatment related side effects. The aim was to prospectively analyze HR-QoL, changes in clinical variables and the impact of OM on HR-QoL during HNC treatment.

Materials and methods
Patients were recruited before commencing curative cancer treatment and were given professional oral care weekly during oncologic treatment. HR-QoL was reported before, during (week 2, 4 and 6) and three months after treatment using the EORTC Quality of Life questionnaires C30 and H&N35 and the stimulated whole salivary secretion rate was determined at the same time-points. OM (erythema and ulceration) was registered using the Oral Mucositis Assessment Scale (OMAS), at baseline, weekly during treatment and post treatment. Differences in HR-QoL between different timepoints were analyzed. To analyze the impact of OM on HR-QoL the patients were categorized into two groups: no/mild OM (OMAS ulceration score 0–1) or severe OM (OMAS ulceration score ≥ 2) and HR-QoL was compared between the two OM groups at three timepoints during treatment.

Results
Fifty-seven patients (43 men, 14 women), with a mean age of 58 years were included. Patients reported progressively impaired HR-QoL, with peak issues noted at weeks 4 and 6, particularly in social eating, senses, appetite loss, sticky saliva, and decreasing salivary secretion rates were determined. Patients with severe OM reported worse HR-QoL compared to those with no/mild OM. Persistent problems 3 months post treatment were appetite loss, dry mouth, senses (smell and taste) and problems with social eating.

Conclusion
Patients experienced exacerbated symptoms and problems weeks 4 and 6 of oncological treatment, especially among those with severe OM, stressing the importance of clinically monitoring the patients to reduce and alleviate their symptoms. Persistent problems three months post treatment are likely associated with the reduced salivary secretion rate indicating that patients should be monitored also after completed oncological treatment.
Assisted reproductive technology (ART) patient information-seeking behavior: a qualitative study
Authors: Mayette Emma , Scalise Ariel , Li Angela , McGeorge Nicolette , James Kaitlyn , Mahalingaiah Shruthi 
Published: June 2024

Abstract
Background
Approximately 13% of women in the United States of reproductive age seek infertility services. Assisted reproductive technology (ART), including in vitro fertilization, is used to help patients achieve pregnancy. Many people are not familiar with these treatments prior to becoming patients and possess knowledge gaps about care.

Methods
This study employed qualitative methods to investigate how patients interact with information sources during care. Patients who underwent ART including embryo transfer between January 2017 and April 2022 at a large urban healthcare center were eligible. Semi-structured, in-depth interviews were conducted between August and October 2022. Fifteen females with an average age of 39 years participated. Reflexive thematic analysis was performed.

Results
Two main themes emerged. Participants (1) utilized clinic-provided information and then turned to outside sources to fill knowledge gaps; (2) struggled to learn about costs, insurance, and mental health resources to support care. Participants preferred clinic-provided resources and then utilized academic sources, the internet, and social media when they had unfulfilled information needs. Knowledge gaps related to cost, insurance, and mental health support were reported.

Conclusion
ART clinics can consider providing more information about cost, insurance, and mental health support to patients.

Trial registration
The Massachusetts General Hospital Institutional Review Board approved this study (#2022P000474) and informed consent was obtained from each participant.
Catechin-Induced changes in PODXL, DNMTs, and miRNA expression in Nalm6 cells: an integrated in silico and in vitro approach
Authors: Afgar Ali , Keyhani Alireza , Afgar Amirreza , Mirzaei-Parsa Mohamad Javad , Kermani Mahdiyeh Ramezani Zadeh , Rezaei Masoud , Ebrahimipour Mohammad , Langroudi Ladan , Bardsiri Mahla Sattarzadeh , Vahidi Reza 
Published: June 2024

Abstract
Background
This study explored the impact of predicted miRNAs on DNA methyltransferases (DNMTs) and the PODXL gene in Nalm6 cells, revealing the significance of these miRNAs in acute lymphocytic leukemia (ALL).

Methods
A comprehensive approach was adopted, integrating bioinformatic analyses encompassing protein structure prediction, molecular docking, dynamics, and ADMET profiling, in conjunction with evaluations of gene and miRNA expression patterns. This methodology was employed to elucidate the therapeutic potential of catechin compounds in modulating the activity of DNA methyltransferases (DNMTs) and the PODXL gene.

Results
The findings from our investigation indicate that catechins possess the capability to inhibit DNMT enzymes. This inhibitory effect is associated with the upregulation of microRNAs miR-200c and miR-548 and a concurrent downregulation of PODXL gene expression. These molecular interactions culminate in an augmented apoptotic response within ALL (Nalm6) cells.

Conclusion
The study posits that catechins may represent a viable therapeutic avenue for inducing apoptosis in ALL cells. This is achieved through the modulation of epigenetic mechanisms and alterations in gene expression profiles, highlighting the potential of catechins as agents for cancer therapy.
Re-engaging with arts and cultural activities at the Life Rooms: ‘It’s given me spring’
Authors: Worsley Joanne , Billington Josie , Balabanova Ekaterina 
Published: June 2024

Abstract
Background
Mersey Care NHS Foundation Trust’s Life Rooms initiative is an established and successful model of integrating arts and culture within NHS provision. In the face of COVID-19, the Life Rooms was restructured to provide a full suite of online resources. Following the lifting of restrictions, in-person arts provision returned to the Life Rooms sites. Additional evidence in respect of the impact on mental health and wellbeing of the return to in-person arts and cultural activities provided by the Life Rooms, as well as the relative merits of online and in-person arts and cultural activities, is needed to inform future planning around in-person, online, and/or hybrid provision.

Methods
Interviews with practitioners delivering cultural and creative courses at the Life Rooms (n = 8) and users of the Life Rooms (n = 5) were conducted to explore the impact of the return to in-person arts provision at the Life Rooms, as well as the merits of online and in-person arts provision. Data were analysed using thematic analysis.

Results
Three overarching themes were identified: ‘Provision, access, and reach’; ‘Value of arts and creativity’; and ‘Challenges with the Life Rooms model in the new normal’. The findings demonstrate the critical role of arts and cultural provision in providing stigma-free environments to reconnect the vulnerable and isolated. As re-engagement remained slow, there is a need to be responsive to hesitation around re-engaging in-person. The Life Rooms online learning offer remained vital for those who are vulnerable or otherwise unable to access in-person activities.

Conclusions
As our findings show a demand for maintaining online provision that enables accessibility together with in-person provision that boosts community connectedness, ensuring continued online access alongside in-person delivery should be prioritised. As mental health demands could continue to grow in coming years as the pandemic evolves, in-person arts engagement could have an important role in meeting mental health needs.
Cultural competences among future nurses and midwives: a case of attitudes toward Jehovah’s witnesses’ stance on blood transfusion
Authors: Domaradzki Jan , Głodowska Katarzyna , Doron Einat , Markwitz-Grzyb Natalia , Jabkowski Piotr 
Published: June 2024

Abstract
Background
Transcultural nursing recognises the significance of cultural backgrounds in providing patients with quality care. This study investigates the opinions of master’s students in nursing and midwifery regarding the attitudes of Jehovah’s Witnesses towards refusing blood transfusions.

Methods
349 master’s students in nursing and midwifery participated in a quantitative study and were surveyed via the Web to evaluate their awareness of the stance of Jehovah’s Witnesses on blood transfusions and the ethical and legal dilemmas associated with caring for Jehovah’s Witness (JW) patients.

Results
The study yielded three significant findings. It unequivocally demonstrates that nursing and midwifery students possess inadequate knowledge regarding Jehovah’s Witnesses’ stance on blood transfusions and their acceptance of specific blood products and medical procedures. Despite being cognisant of the ethical and legal dilemmas of caring for JW patients, students lack an understanding of patients’ autonomy to reject blood transfusions and their need for bloodless medicine. Students also articulated educational needs regarding cultural competencies regarding the Jehovah’s Witnesses’ beliefs on blood transfusions and non-blood management techniques.

Conclusions
Healthcare professionals need the knowledge and skills necessary to provide holistic, patient-centred and culturally sensitive care. This study emphasises the urgent need for university curricula and nursing postgraduate training to include modules on transcultural nursing and strategies for minimising blood loss.
Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B-associated dysplasia: an important distinction
Authors: Shirodkar Diksha , Smithson Sarah Francesca , Keen Richard , Lester Tracy , Banos-Pinero Benito , Burren Christine Pamela 
Published: June 2024

Abstract
Background
Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis.

Case presentation
A three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother’s persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition).

Conclusion
This report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways.
Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation
Authors: Zhang Fengqin , Yue Huihui , Dong Ruihan , He Jianhan , Zhou Ling , Dou Xinran , Wang lingling , Zheng Pengdou , Mao Zhenyu , Zhu Xiaoyan , Wang Yi , Liu Huiguo , Zhang Huilan 
Published: June 2024

Abstract
Background
Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it’s unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear.

Methods
To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions.

Results
In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts.

Conclusion
In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.
Incident heart failure and the subsequent risk of progression to end stage kidney disease in individuals with type 2 diabetes
Authors: Liu Sylvia , Liu Jian-Jun , Ang Keven , Lee Janus , Chan Clara , Gurung Resham L. , Zheng Huili , Tang Justin , Lim Su Chi 
Published: June 2024

Abstract
Background
Diabetic kidney disease is an established risk factor for heart failure. However, the impact of incident heart failure on the subsequent risk of renal failure has not been systematically assessed in diabetic population. We sought to study the risk of progression to end stage kidney disease (ESKD) after incident heart failure in Asian patients with type 2 diabetes.

Methods
In this prospective cohort study, 1985 outpatients with type 2 diabetes from a regional hospital and a primary care facility in Singapore were followed for a median of 8.6 (interquartile range 6.2–9.6) years. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m2, maintenance dialysis or renal death, whichever occurred first.

Results
180 incident heart failure events and 181 incident ESKD events were identified during follow-up. Of 181 ESKD events, 38 (21%) occurred after incident heart failure. Compared to those did not progress to ESKD after incident heart failure (n = 142), participants who progressed to ESKD after heart failure occurrence were younger, had higher HbA1c and higher urine albumin-to-creatinine ratio at baseline. The excess risk of ESKD manifested immediately after heart failure occurrence, persisted for two years and was moderated thereafter. Cox regression suggested that, compared to counterparts with no heart failure event, participants with heart failure occurrence had 9.6 (95% CI 5.0- 18.3) fold increased risk for incident ESKD after adjustment for baseline cardio-renal risk factors including eGFR and albuminuria. It appeared that heart failure with preserved ejection fraction had a higher risk for ESKD as compared to those with reduced ejection fraction (adjusted HR 13.7 [6.3–29.5] versus 6.5 [2.3–18.6]).

Conclusion
Incident heart failure impinges a high risk for progression to ESKD in individuals with type 2 diabetes. Our data highlight the need for intensive surveillance of kidney function after incident heart failure, especially within the first two years after heart failure diagnosis.
Integrated pathway mining and selection of an artificial CYP79-mediated bypass to improve benzylisoquinoline alkaloid biosynthesis
Authors: Takenaka Musashi , Kamasaka Kouhei , Daryong Kim , Tsuchikane Keiko , Miyazawa Seiha , Fujihana Saeko , Hori Yoshimi , Vavricka Christopher J. , Hosoyama Akira , Kawasaki Hiroko , Shirai Tomokazu , Araki Michihiro , Nakagawa Akira , Minami Hiromichi , Kondo Akihiko , Hasunuma Tomohisa 
Published: June 2024

Abstract
Background
Computational mining of useful enzymes and biosynthesis pathways is a powerful strategy for metabolic engineering. Through systematic exploration of all conceivable combinations of enzyme reactions, including both known compounds and those inferred from the chemical structures of established reactions, we can uncover previously undiscovered enzymatic processes. The application of the novel alternative pathways enables us to improve microbial bioproduction by bypassing or reinforcing metabolic bottlenecks. Benzylisoquinoline alkaloids (BIAs) are a diverse group of plant-derived compounds with important pharmaceutical properties. BIA biosynthesis has developed into a prime example of metabolic engineering and microbial bioproduction. The early bottleneck of BIA production in Escherichia coli consists of 3,4-dihydroxyphenylacetaldehyde (DHPAA) production and conversion to tetrahydropapaveroline (THP). Previous studies have selected monoamine oxidase (MAO) and DHPAA synthase (DHPAAS) to produce DHPAA from dopamine and oxygen; however, both of these enzymes produce toxic hydrogen peroxide as a byproduct.

Results
In the current study, in silico pathway design is applied to relieve the bottleneck of DHPAA production in the synthetic BIA pathway. Specifically, the cytochrome P450 enzyme, tyrosine N-monooxygenase (CYP79), is identified to bypass the established MAO- and DHPAAS-mediated pathways in an alternative arylacetaldoxime route to DHPAA with a peroxide-independent mechanism. The application of this pathway is proposed to result in less formation of toxic byproducts, leading to improved production of reticuline (up to 60 mg/L at the flask scale) when compared with that from the conventional MAO pathway.

Conclusions
This study showed improved reticuline production using the bypass pathway predicted by the M-path computational platform. Reticuline production in E. coli exceeded that of the conventional MAO-mediated pathway. The study provides a clear example of the integration of pathway mining and enzyme design in creating artificial metabolic pathways and suggests further potential applications of this strategy in metabolic engineering.
A five years malaria surveillance data analysis of North Shewa zone, Amhara region, Ethiopia: July 2018 to June 2023
Authors: Moltot Tebabere , Bekele Girma , Gebreegziabher Zenebe Abebe , Lemma Tesfansh , Sisay Moges , Silesh Mulualem , Mulugeta Melkam , Demissie Legesse , Kebede Tirusew Nigussie , Taye Birhan Tsegaw 
Published: June 2024

Abstract
Background
Malaria is a critical public health concern in Ethiopia, with significant socioeconomic consequences. Malaria data trend analysis is essential for understanding transmission patterns and adopting evidence-based malaria control measures. The purpose of this study was to determine the 5 year distribution of malaria in North Shewa zone, Amhara region, Ethiopia, in 2023.

Methods
A descriptive cross-sectional study design was employed to analyse the 5 year trend of malaria surveillance data in the North Shewa zone of the Amhara regional, Ethiopia, spanning from July 2018 to June 2023. The malaria indicator data were gathered from the zone’s public health emergency management database. Malaria data from the previous 5 years was collected, compiled, processed, and analysed using Microsoft Excel 2019.

Results
Among a total of 434,110 suspected cases 47,889 (11.03%) cases were confirmed as malaria, with an average annual malaria incidence rate of 4.4 per 1000 population in the Zone. Malaria cases exhibited an increase from Epidemiological Week (Epi week) 37 to Epi week 49 (September to November) and again from Epi week 22 to week 30 (May to July). Individuals aged 15 and above, and all districts in the Zone except Angolela were notably affected by malaria.

Conclusion
Despite implementing various measures to reduce malaria incidence, the disease continues to persist in the zone. Therefore, the Zone Health Department should intensify its preventive and control efforts.
Inhibition of WNT/β-catenin signalling during sex-specific gonadal differentiation is essential for normal human fetal testis development
Authors: Lundgaard Riis Malene , Delpouve Gaspard , Nielsen John E. , Melau Cecilie , Langhoff Thuesen Lea , Juul Hare Kristine , Dreisler Eva , Aaboe Kasper , Tutein Brenøe Pia , Albrethsen Jakob , Frederiksen Hanne , Juul Anders , Giacobini Paolo , Jørgensen Anne 
Published: June 2024

AbstractSex-specific gonadal differentiation is directed by complex signalling promoting development in either male or female direction, while simultaneously inhibiting the opposite pathway. In mice, the WNT/β-catenin pathway promotes ovarian development and the importance of actively inhibiting this pathway to ensure normal testis development has been recognised. However, the implications of alterations in the tightly regulated WNT/β-catenin signalling during human fetal gonad development has not yet been examined in detail. Thus, the aim of this study was to examine the consequences of dysregulating the WNT/β-catenin signalling pathway in the supporting cell lineage during sex-specific human fetal gonad development using an established and extensively validated ex vivo culture model. Inhibition of WNT/β-catenin signalling in human fetal ovary cultures resulted in only minor effects, including reduced secretion of RSPO1 and reduced cell proliferation although this was not consistently found in all treatment groups. In contrast, promotion of WNT/β-catenin signalling in testes severely affected development and function. This included disrupted seminiferous cord structures, reduced cell proliferation, reduced expression of SOX9/AMH, reduced secretion of Inhibin B and AMH as well as loss of the germ cell population. Additionally, Leydig cell function was markedly impaired with reduced secretion of testosterone, androstenedione and INSL3. Together, this study suggests that dysregulated WNT/β-catenin signalling during human fetal gonad development severely impairs testicular development and function. Importantly, our study highlights the notion that sufficient inhibition of the opposite pathway during sex-specific gonadal differentiation is essential to ensure normal development and function also applies to human fetal gonads.