bluuebunny/crossref_metadata_2025_split huggingface dataset:
Women’s acceptability of a self-collect HPV same-day screen-and-treat program in a high burden setting in the Pacific
Authors: Camara Hawa , Nosi Somu , Munnull Gloria , Badman Steven G. , Bolgna John , Kuk Joseph , Mola Glen , Guy Rebecca , Vallely Andrew J. , Kelly-Hanku Angela 
Published: December 2022

Abstract
Background
A field trial to evaluate a self-collect point-of-care HPV screen-and-treat (HPV S&T) program was implemented in two Well Women Clinics in Papua New Guinea (Papua New Guinea). Assessing the acceptability of a health intervention is a core element of evaluation. In this study, we examined women’s acceptability of both self-collection and HPV S&T intervention in Papua New Guinea.

Methods
Sixty-two semi-structured interviews were conducted with women who had undergone cervical screening in the same-day self-collected HPV screen-and-treat program in Madang and Western Highlands Provinces, Papua New Guinea. Data were thematically analysed using the Theoretical Framework of Acceptability (TFA) and managed using NVivo 12.5.

Results
Most women agreed that self-collection was transformative: it helped circumvent the culturally embarrassing pelvic examination and increased their self-efficacy, especially due to the provision of health education, instructions, and pictorial aids. The availability of same-day results, and treatment if indicated, was particularly valued by the women because it reduced the financial and temporal burden to return to the clinic for results. It also meant they did not need to wait anxiously for long periods of time for their results. Women also appreciated the support from, and expertise of, health care workers throughout the process and spoke of trust in the HPV-DNA testing technology. Most women were willing to pay for the service to ensure its sustainability and timely scale-up throughout Papua New Guinea to support access for women in harder to reach areas.

Conclusion
This study reported very high levels of acceptability from a field trial of self-collection and HPV same-day screen-and-treat. The program was deemed culturally congruent and time efficient. This innovative cervical screening modality could be the ‘solution’ needed to see wider and more immediate impact and improved outcomes for women in Papua New Guinea and other high-burden, low-resource settings.
Duty to treat and perceived risk of contagion during the COVID-19 pandemic: Norwegian physicians’ perspectives and experiences—a questionnaire survey
Authors: Isaksson Rø Karin , Magelssen Morten , Bååthe Fredrik , Miljeteig Ingrid , Bringedal Berit 
Published: December 2022

AbstractBackgroundThe COVID-19 pandemic actualised the dilemma of how to balance physicians´ obligation to treat patients and their own perceived risk of being infected. To discuss this in a constructive way we need empirical studies of physicians´ views of this obligation.MethodsA postal questionnaire survey was sent to a representative sample of Norwegian physicians in December 2020. We measured their perceived obligation to expose themselves to infection, when necessary, in order to provide care, concerns about being infected themselves, for spreading the virus to patients or to their families. We used descriptive statistics, chi-square tests and logistic regression analyses.ResultsThe response rate was 1639/2316 (70.9%), 54% women. Of doctors < 70, 60,2% (95% CI 57.7–62.7) acknowledged to some or a large degree an obligation to expose themselves to risk of infection, and 42.0% (39.5–44.5) held this view despite a scarcity of personal protective equipment (PPE). Concern about being infected oneself to some or to a large extent was reported by 42.8% (40.3–45.3), 47.8% (45.3–50.3) reported concern about spreading the virus to patients, and 63.9% (61.5–66.3) indicated worry about spreading it to their families. Being older increased the odds of feeling obligated (ExpB = 1.02 p < 0.001), while experiencing scarcity of PPE decreased the odds (ExpB = 0.74, p = 0.01). The odds of concern about spreading virus to one´s family decreased with higher age (Exp B = 0.97, p < 0.001), increased with being female (Exp B = 1.44, p = 0.004), and perceived lack of PPE (Exp B = 2.25, p < 0.001). Although more physicians working in COVID-exposed specialties experienced scarcity of PPE and reported perceived increased risks for health personnel, the odds of concern about being infected themselves or spreading the virus to their families were not higher than for other doctors.ConclusionThese empirical findings lead to the question if fewer physicians in the future will consider the duty to treat their top priority. This underscores the need to revisit and revitalise existing ethical codes to handle the dilemma between physicians´ duty to treat versus the duty to protect physicians and their families. This is important for the ability to provide good care for the patient and the provider in a future pandemic situation.
Recent advances in the improvement of cyanobacterial enzymes for bioalkane production
Authors: Hayashi Yuuki , Arai Munehito 
Published: December 2022

AbstractThe use of biologically produced alkanes has attracted considerable attention as an alternative energy source to petroleum. In 2010, the alkane synthesis pathway in cyanobacteria was found to include two small globular proteins, acyl-(acyl carrier protein [ACP]) reductase (AAR) and aldehyde deformylating oxygenase (ADO). AAR produces fatty aldehydes from acyl-ACPs/CoAs, which are then converted by ADO to alkanes/alkenes equivalent to diesel oil. This discovery has paved the way for alkane production by genetically modified organisms. Since then, many studies have investigated the reactions catalyzed by AAR and ADO. In this review, we first summarize recent findings on structures and catalytic mechanisms of AAR and ADO. We then outline the mechanism by which AAR and ADO form a complex and efficiently transfer the insoluble aldehyde produced by AAR to ADO. Furthermore, we describe recent advances in protein engineering studies on AAR and ADO to improve the efficiency of alkane production in genetically engineered microorganisms such as Escherichia coli and cyanobacteria. Finally, the role of alkanes in cyanobacteria and future perspectives for bioalkane production using AAR and ADO are discussed. This review provides strategies for improving the production of bioalkanes using AAR and ADO in cyanobacteria for enabling the production of carbon–neutral fuels.
Transcriptomic landscape of TIMP3 oncosuppressor activity in thyroid carcinoma
Authors: Mazzoni M. , Todoerti K. , Agnelli L. , Minna E. , Pagliardini S. , Di Marco T. , Borrello M. G. , Neri A. , Greco A. 
Published: December 2022

Abstract
Background
Papillary thyroid cancer (PTC) is the most frequent thyroid tumor. The tissue inhibitor of metalloproteinase-3 (TIMP3) gene encodes a matrix metalloproteinases inhibitor that exerts a tumor suppressor role in several tumor types. TIMP3 is frequently downregulated in PTC by promoter methylation. We have previously functionally demonstrated that TIMP3 exerts an oncosuppressor role in PTC: TIMP3 restoration in the PTC-derived NIM1 cell line affects in vitro migration, invasion and adhesive capability, while reduces tumor growth, angiogenesis and macrophage recruitment in vivo. To get a deeper insight on the mediators of TIMP3 oncosuppressor activity in thyroid tumors, here we focused on the TIMP3 related transcriptome.

Methods
TCGA database was used for investigating the genes differentially expressed in PTC samples with low and high TIMP3 expression. Genome wide expression analysis of clones NIM1-T23 (expressing a high level of TIMP3 protein) and NIM1-EV (control empty vector) was performed. Gene sets and functional enrichment analysis with clusterProfiler were applied to identify the modulated biological processes and pathways. CIBERSORT was used to evaluate the distribution of different immunological cell types in TCGA-PTC tumor samples with different TIMP3 expression levels. Real time PCR was performed for the validation of selected genes.

Results
Thyroid tumors with TIMP3-high expression showed a down-modulation of inflammation-related gene sets, along with a reduced protumoral hematopoietic cells fraction; an enrichment of cell adhesion functions was also identified. Similar results were obtained in the TIMP3-overexpessing NIM1 cells in vitro model, where a down-regulation of immune-related function gene sets, some of which also identified in tumor samples, was observed. Interestingly, through enrichment analysis, were also recognized terms related to cell adhesion, extracellular matrix organization, blood vessel maintenance and vascular process functions that have been found modulated in our previous in vitro and in vivo functional studies.

Conclusions
Our results highlight the correlation of TIMP3 expression levels with the regulation of inflammatory functions and the immune infiltration composition associated with different PTC prognosis, thus providing a broader view on the oncosuppressor role of TIMP3 in PTC.
3D printed polylactic acid/gelatin-nano-hydroxyapatite/platelet-rich plasma scaffold for critical-sized skull defect regeneration
Authors: Bahraminasab Marjan , Doostmohammadi Nesa , Talebi Athar , Arab Samaneh , Alizadeh Akram , Ghanbari Ali , Salati Amir 
Published: December 2022

AbstractBackgroundThree-dimensional (3D) printing is a capable approach for the fabrication of bone tissue scaffolds. Nevertheless, a purely made scaffold such as polylactic acid (PLA) may suffer from shortcomings and be restricted due to its biological behavior. Gelatin, hydroxyapatite and platelet-rich plasma (PRP) have been revealed to be of potential to enhance the osteogenic effect. In this study, it was tried to improve the properties of 3D-printed PLA scaffolds by infilling them with gelatin-nano-hydroxyapatite (PLA/G-nHA) and subsequent coating with PRP. For comparison, bare PLA and PLA/G-nHA scaffolds were also fabricated. The printing accuracy, the scaffold structural characterizations, mechanical properties, degradability behavior, cell adhesion, mineralization, systemic effect of the scaffolds on the liver enzymes, osteocalcin level in blood serum and in vivo bone regeneration capability in rat critical-sized calvaria defect were evaluated.ResultsHigh printing accuracy (printing error of < 11%) was obtained for all measured parameters including strut thickness, pore width, scaffold density and porosity%. The highest mean ultimate compression strength (UCS) was associated with PLA/G-nHA/PRP scaffolds, which was 10.95 MPa. A slow degradation rate was observed for all scaffolds. The PLA/G-nHA/PRP had slightly higher degradation rate, possibly due to PRP release, with burst release occurred at week 4. The MTT results showed that PLA/G-nHA/PRP provided the highest cell proliferation at all time points, and the serum biochemistry (ALT and AST level) results indicated no abnormal/toxic influence caused by scaffold biomaterials. Superior cell adhesion and mineralization were obtained for PLA/G-nHA/PRP. Furthermore, all the developed scaffolds showed bone repair capability. The PLA/G-nHA/PRP scaffolds could better support bone regeneration than bare PLA and PLA/G-nHA scaffolds.ConclusionThe PLA/G-nHA/PRP scaffolds can be considered as potential for hard tissue repair.
Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study
Authors: Omi Yoko , Haniu Kento , Kamio Hidenori , Fujimoto Mikiko , Yoshida Yusaku , Horiuchi Kiyomi , Okamoto Takahiro 
Published: December 2022

Abstract
Introduction
Non-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.

Materials and methods
PTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.

Results
Pathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.

Conclusion
The prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.
A call for culture-centred care: exploring health workers' perspectives of positive care experiences and culturally responsive care provision to Aboriginal women and their infants in mainstream health in South Australia
Authors: Sivertsen Nina , Deverix Janiene , Gregoric Carolyn , Grant Julian 
Published: December 2022

AbstractBackgroundAboriginal women and their infants experience significant disadvantage in health outcomes compared to their non-Aboriginal counterparts. Access to timely, effective, and appropriate maternal and child health care can contribute to reducing these existing health disparities. This research sought to explore factors that contribute to continuity of care for Aboriginal women and their infants living in metropolitan South Australia. This paper reports on the perspectives of health care workers in mainstream health services from the antenatal period to the end of an infants’ second birthday. It explores health workers’ perspectives of what contributes to positive care experiences and satisfaction with care provided to Aboriginal women and their infants in mainstream health.MethodsEight focus groups were held with 52 health professionals. Participants included Aboriginal Cultural Child and Family Support Consultants (n = 7), Aboriginal Maternal Infant Care Workers (n = 3), Midwives (n = 3) and Child and Family Nurses (n = 39). Data was inductively coded and thematically analysed.ResultsThree key themes emerged: the system takes priority, culture is not central in approaches to care, and ‘we’ve got to be allowed to do it in a different way’.ConclusionsThis research highlights a lack of continuity of care for Aboriginal families accessing mainstream health services from the antenatal period through to an infants’ first 1000 days of life. This research has implications for communities, and it calls for strategies to enhance continuity, and healthcare services to provide appropriate and culturally safe care. Findings will inform and guide future changes to improve continuity of care for Aboriginal families and infants in the first 1000 days.
Cost utility and budget impact analysis of dexamethasone compared with bortezomib and lenalidomide for the treatment of second line multiple myeloma from a South African public health perspective
Authors: Matsela Lineo Marie , Cleary Susan , Wilkinson Thomas 
Published: December 2022

Abstract
Background
Multiple myeloma is an incurable haematological malignancy that is associated with a high probability of relapse. The survival of relapsed patients has been greatly improved by the development of novel drugs such as lenalidomide and bortezomib. We assessed the cost-effectiveness of these drugs as second-line treatment for relapsed/refractory multiple myeloma (RRMM) patients in the South African public health care system.

Methods
We modelled 3 treatment strategies for second-line RRMM treatment: dexamethasone (standard of care), bortezomib (BORT) and lenalidomide plus dexamethasone (LEN/DEX) from the South African public health perspective. For each strategy we modelled a hypothetical cohort of relapsed/refractory multiple myeloma patients using a three-state Markov model over a 15-year time horizon. Efficacy and utilization data were obtained from the MM009/010 and APEX trials and external studies. Price and cost data were from local sources and presented in 2021 South African Rands. Outcomes were reported in quality adjusted life years (QALYs). Incremental cost effectiveness ratios (ICERs) were calculated for BORT and LEN/DEX and compared to a local cost-effectiveness threshold of R38 500 per DALY averted using the assumption that 1 DALY averted is equal to 1 QALY gained. A budget impact analysis was conducted to evaluate the financial impact of the introduction of BORT and LEN/DEX, respectively. Deterministic sensitivity analysis was undertaken to account for parameter uncertainties.

Results
The modelled total costs of DEX, BORT and LEN/DEX were estimated to be R8 312, R234 996 and R1 135 323, respectively. DEX treatment provided 1.14 QALYs while BORT and LEN/DEX treatments provided 1.49 and 2.22 QALYs, respectively. The ICER of BORT versus DEX was R654 649 and that of LEN/DEX versus BORT was R1 225 542. Both BORT and LEN/DEX treatments were not cost-effective relative to a cost-effectiveness threshold of R38 500 per DALY averted. Both BORT and LEN/DEX significantly increase the 1 year budget-cost of RRMM treatment.

Conclusion
Both BORT and LEN/DEX treatments are unlikely to be cost-effective strategies for second-line treatment of RRMM in South Africa. The results indicate that the drug prices of lenalidomide and bortezomib are key drivers of value for money. Price reductions could potentially make BORT more cost-effective.
Case report: surgical management of symptomatic pretracheal thyroid gland in a patient with dual ectopic thyroid
Authors: Saito Masayuki , Banno Hirona , Ito Yukie , Ido Mirai , Goto Manami , Ando Takahito , Kousaka Junko , Mouri Yukako , Fujii Kimihito , Imai Tsuneo , Nakano Shogo , Tsuzuki Toyonori 
Published: December 2022

Abstract
Background
Dual ectopic thyroid, a very rare condition, is defined as the simultaneous presence of ectopic thyroid tissue in two abnormal locations. Here, we report the surgical management of a patient with dual ectopic thyroid.

Case presentation
The patient was a 12-year-old boy with right para-midline swelling for 2 months. On physical examination of the upper anterior neck, there was a 4 cm × 3 cm mass that was soft, mobile, smooth, and painless. Blood examination showed euthyroidism. Neck ultrasonography showed a well-circumscribed multilocular cyst. We followed up by observation only because the patient had no local symptoms or malignancy. After 2 years, the mass gradually enlarged, so we performed surgery to improve cosmetic outcomes. Preoperative neck CT revealed both a high-density solid mass at the base of the tongue and a central low-density region surrounded by a high-density area at the pretracheal region below the hyoid. The infrahyoid mass was surgically removed, and the sublingual mass was left intact. Pathological findings showed the growth of multiple-size follicles, leading to a diagnosis of adenomatous goiter. Postoperative 123−I scintigraphy showed radioactive iodine uptake in the sublingual lesion, but none in the normal thyroid bed despite the extirpation of thyroid tissue. Postoperative thyroid hormone replacement was started for subclinical hypothyroidism. One year postoperatively, the patient became euthyroid.

Conclusion
Surgical excision was used to manage a symptomatic cervical infrahyoid mass related to dual ectopic thyroid. Postoperatively, thyroid hormone replacement was required both to prevent enlargement of the remaining sublingual thyroid and to maintain adequate thyroid hormone levels.
Distance-dependent inhibition of translation initiation by downstream out-of-frame AUGs is consistent with a Brownian ratchet process of ribosome scanning
Authors: Li Ke , Kong Jinhui , Zhang Shuo , Zhao Tong , Qian Wenfeng 
Published: December 2022

Abstract
Background
Eukaryotic ribosomes are widely presumed to scan mRNA for the AUG codon to initiate translation in a strictly 5′–3′ movement (i.e., strictly unidirectional scanning model), so that ribosomes initiate translation exclusively at the 5′ proximal AUG codon (i.e., the first-AUG rule).

Results
We generate 13,437 yeast variants, each with an ATG triplet placed downstream (dATGs) of the annotated ATG (aATG) codon of a green fluorescent protein. We find that out-of-frame dATGs can inhibit translation at the aATG, but with diminishing strength over increasing distance between aATG and dATG, undetectable beyond ~17 nt. This phenomenon is best explained by a Brownian ratchet mechanism of ribosome scanning, in which the ribosome uses small-amplitude 5′–3′ and 3′–5′ oscillations with a net 5′–3′ movement to scan the AUG codon, thereby leading to competition for translation initiation between aAUG and a proximal dAUG. This scanning model further predicts that the inhibitory effect induced by an out-of-frame upstream AUG triplet (uAUG) will diminish as uAUG approaches aAUG, which is indeed observed among the 15,586 uATG variants generated in this study. Computational simulations suggest that each triplet is scanned back and forth approximately ten times until the ribosome eventually migrates to downstream regions. Moreover, this scanning process could constrain the evolution of sequences downstream of the aATG to minimize proximal out-of-frame dATG triplets in yeast and humans.

Conclusions
Collectively, our findings uncover the basic process by which eukaryotic ribosomes scan for initiation codons, and how this process could shape eukaryotic genome evolution.