bluuebunny/crossref_metadata_2025 huggingface dataset:
Unit cost repositories for health program planning and evaluation: a report on research in practice with lessons learned
Authors: Bollinger Lori A. , Corlis Joseph , Ombam Regina , Forsythe Steven , Resch Stephen C.
Published: June 2023

Background

Most low- and middle-income countries have limited access to cost data that meets the needs of health policy-makers and researchers in health intervention areas including HIV, tuberculosis, and immunization. Unit cost repositories (UCRs)—searchable databases that systematically codify evidence from costing studies—have been developed to reduce the effort required to access and use existing costing information. These repositories serve as public resources and standard references, which can improve the consistency and quality of resource needs projections used for strategic planning and resource mobilization. UCRs also enable analysis of cost determinants and more informed imputation of missing cost data. This report examines our experiences developing and using seven UCRs (two global, five country-level) for cost projection and research purposes.

Discussion

We identify advances, challenges, enablers, and lessons learned that might inform future work related to UCRs. Our lessons learned include: (1) UCRs do not replace the need for costing expertise; (2) tradeoffs are required between the degree of data complexity and the useability of the UCR; (3) streamlining data extraction makes populating the UCR with new data easier; (4) immediate reporting and planning needs often drive stakeholder interest in cost data; (5) developing and maintaining UCRs requires dedicated staff time; (6) matching decision-maker needs with appropriate cost data can be challenging; (7) UCRs must have data quality control systems; (8) data in UCRs can become obsolete; and (9) there is often a time lag between the identification of a cost and its inclusion in UCRs.

Conclusions

UCRs have the potential to be a valuable public good if kept up-to-date with active quality control and adequate support available to end-users. Global UCR collaboration networks and greater control by local stakeholders over global UCRs may increase active, sustained use of global repositories and yield higher quality results for strategic planning and resource mobilization.
Current state, equality level and trends of self-rated health among old adults with intact physical condition
Authors: Ren Weicun , Tarimo Clifford Silver , Liang Zhang
Published: June 2023

Background

Self-rated health among old adults (SHOA) indicates individuals' subjective assessments and evaluations of their overall health based on objective physical circumstances. The purpose of this study was to analyze the current state and influencing factors of the subjective perception-based self-rated health (SH) by qualifying selected older adults with similar objective physical conditions, as well as to explore the equality and changing trends of SHOA based on influencing factors.

Methods

This study designed a cross-sectional study, conducted in three provinces in east, central and west China, and included 1,153 older adults (> = 60 years) with intact physical condition (IPC). The current state of SHOA and its influencing factors were analyzed using mean comparisons and Logistic regression (LR) models. The equality level and trend of SHOA's effect on health literacy, health habits, and access to health care were determined using the Lorenz curve, Gini coefficient, and Vector Autoregression (VAR) model.

Results

The mean SHOA with IPC was 74.37 ± 13.22. Findings from LR modeling indicated that SHOA with IPC was mainly influenced by age and communication methods (P < 0.05). It was also observed that the total Gini coefficient of the allocation of SHOA with IPC based on communication methods was equal to 0.0188, and the VAR results showed that the total effect of change in SHOA on health literacy among older adults was negative and its duration of the effect exceeded 50.

Conclusions

The SHOA with IPC was shown to be better and was primarily influenced by age and communication methods. The observed effect of SHOA on health literacy was negative and lasting. To improve SHOA with IPC even further, policymakers could consider promoting the use of modern and convenient communication methods (such as smartphones) through training and purchasing subsidies, as well as focusing on increasing sustained attention and promoting health literacy and behavior among older adults with improved SH.
An integrated approach to health, wellbeing, and productivity at work: a design of a stepped wedge worksite intervention study
Authors: Korshøj Mette , Poulsen Vivian Rueskov , Sköld Margrethe Bordado , Autrup Sanna Koch , Oldenburg Brian , Mortensen Ole Steen
Published: June 2023

Background

Despite an intensive focus on workers’ health during recent decades, the prevalence of work-related diseases remains unchanged in Denmark and internationally. Therefore, USA and Australian researchers have initiated new paradigms for integration of health promotion, prevention of work-related disease, and organization of work. Inspired by the Australian WorkHealth Improvement Network program (WIN), this paper describes the background, design, intervention methodologies, and evaluation methods of an Integrated Approach to Health, Wellbeing, and Productivity at Work (ITASPA) intervention aiming to prevent work-related injuries and diseases and promote the health, safety, and wellbeing of the worker.

Methods

Using a stepped wedge design, worksites will be enrolled at baseline and offered the intervention starting at different times. Data will be collected at baseline, before the off-set of the intervention, and after each implementation period. The effect evaluation will be based on a mixed-methods approach. The qualitative data are based on semi-structured interviews and focus groups. The quantitative data consists of questionnaires, anthropometrics, and resting blood pressure and will be analyzed based on the intention-to-treat principle in linear mixed models with random slope and intercept.

Discussion

Integrated interventions are shown to increase overall health and safety at worksites more effectively and rapidly than more narrowly focused programs. Still, previous integrated interventions are lacking successful implementation. In ITASPA, the effects of the intervention is tested in a strong scientific mixed-methods design. Thus, the ITASPA project contributes to the knowledge about what characterizes a best practice for the implementation of integrated worksite interventions.

Trial registration

ITASPA is retrospectively registered in Clinicaltrials.gov on May 19, 2023 (NCT05866978).
Modified unilateral iliac screw fixation with partial reduction in the treatment of high-grade spondylolisthesis at L5/S1 in adult patients: introduction of key technique, report of clinical outcomes and analysis of spinopelvic parameters
Authors: Zhang Yao , Song Jipeng , Lu Yuzheng , Yi Meng , Lin Wancheng , Yao Mingtao , Luo Zhengning , Zhang Genai , Ding Lixiang
Published: June 2023

Background

Management of high-grade spondylolisthesis (HGS) remains challenging. Spinopelvic fixation such as iliac screw (IS) was developed to deal with HGS. However concerns regarding constructs prominence and increased infection-related revision surgery have complicated it’s use. We aim to introduce the modified iliac screw (IS) technique in treating high-grade L5/S1 spondylolisthesis and it’s clinical and radiological outcomes.

Methods

Patients with L5/S1 HGS who underwent modified IS fixation were enrolled. Pre- and postsurgical upright full spine radiographs were obtained to analyze sagittal imbalance, spinopelvic parameters, pelvic incidence-lumbar lordosis mismatch (PI-LL), slip percentage, slip angle (SA), and lumbosacral angle (LSA). Visual analogue scale (VAS), Oswestry disability index (ODI) were evaluated pre- and postoperatively for clinical outcomes assessment. Estimated blood loss, operating time, perioperative complications and revision surgery were documented.

Results

From Jan 2018 to March 2020, 32 patients (15 males) with mean age of 58.66 ± 7.77 years were included. The mean follow-up period was 49 months. The mean operation duration was 171.67 ± 36.66 min. At the last follow-up: (1) the VAS and ODI score were significantly improved (p < 0.05), (2) PI increased by an average of 4.3°, the slip percent, SA and LSA were significantly improved (p < 0.05), (3) four patients (16.7%) with global sagittal imbalance recovered a good sagittal alignment, PI-LL within ± 10° was observed in all patients. One patient experienced wound infection. One patient underwent a revision surgery due to pseudoarthrosis at L5/S1.

Conclusion

The modified IS technique is safe and effective in treating L5/S1 HGS. Sparing use of offset connector could reduce hardware prominence, leading to lower wound infection rate and less revision surgery. The long-term clinical affection of increased PI value is unknown.
Psychometric performance of the Kannada version of sarcopenia quality of life questionnaire (SarQoL®)
Authors: Kumar Prabal , Umakanth Shashikiran , Girish N
Published: June 2023

Background

The Sarcopenia Quality of Life (SarQoL®) is a patient reported quality-of-life questionnaire specific to sarcopenia. In the Indian context, its availability is limited to Hindi, Marathi and Bengali vernacular languages.

Aims

This study aimed to translate, cross-culturally adapt the SarQoL® questionnaire into Kannada and investigate its psychometric properties.

Methods

The SarQoL®-English version was translated into Kannada with the developer’s permission and in accordance with their requirements. To validate the discriminative power, internal consistency and floor and ceiling effect of the SarQoL®-Kannada questionnaire were assessed in the first step. In the second step, the construct validity and the test–retest reliability of the SarQoL®-Kannada was determined.

Result

There was no difficulty in the translation process. A total of n = 114 participants (sarcopenic participants n = 45 and n = 69 non-sarcopenic participants) were included. The good discriminative power of the SarQoL®-Kannada questionnaire {quality of life for sarcopenic subjects [56.43 ± 11.32] vs. non-sarcopenic ones [79.38 ± 8.16], p < 0.001}. High internal consistency (Cronbach’s alpha coefficient was 0.904) and no ceiling/ floor effect were reflected. Excellent test–retest reliability (intraclass correlation coefficient was 0.97, 95% CI 0.92–0.98) were found. A good convergent and divergent validity with similar and different domains of WHOQOL-BREF was observed, while EQ-5D-3L had good convergent and weak divergent validity.

Conclusion

The SarQoL®-Kannada questionnaire is valid, consistent and reliable for the measurement of quality of life of sarcopenic participants. SarQoL®-Kannada questionnaire is now available to be used in clinical practice and as a treatment outcome indicator in research.
Early satisfactory results of percutaneous repair in neglected achilles tendon rupture
Authors: Hammad Mostafa Elsebai , Fayed Aly Maher , Ayoub Mostafa Ahmed , Emran Ali Mahmoud
Published: June 2023

Purpose

This investigation aimed to study the outcome of percutaneous repair of Achilles tendon ruptures regarding patient-reported and objective outcomes.

Methods

This is a retrospective review of a cohort of patients (n = 24) who underwent percutaneous repair of neglected Achilles rupture in the period between 2013 and 2019. Included patients were adults with closed injuries, presented 4–10 weeks after rupture, with intact deep sensation. All underwent clinical examination, X-rays to exclude bony injury and MRI for diagnosis confirmation. All underwent percutaneous repair by the same surgeon, using the same technique and rehabilitation protocol. The postoperative assessment was done subjectively using ATRS and AOFAS score and objectively using a percentage of heel rise comparison to the normal side and calf circumference difference.

Results

The mean follow-up period was 14.85 months ± 3 months. Average AOFAS scores at 6,12 months were 91 and 96, respectively, showing statistically significant improvement from pre-op level (P < 0.001). Percentage of heel rise on the affected side and calf circumference showed statistically significant improvement over the 12 month follow up period (P < 0.001). Superficial infection was reported in two patients (8.3%), and two cases reported transient sural nerve neuritis.

Conclusion

Percutaneous repair of neglected Achilles rupture using the index technique proved a satisfactory patient-reported and objective measurement at a one-year follow-up. With only minor transient complications.
Prevalence, clinical characteristics, and 3-dimensional radiographic analysis of supernumerary teeth in Guangzhou, China: a retrospective study
Authors: He Lidan , Que Guoying , Yang Xiaoxia , Yan Siqi , Luo Song
Published: June 2023

Objective

The aim was to investigate the prevalence and clinical and 3-dimensional (3D) radiographic characteristics of supernumerary teeth (ST) in a paediatric dental population. The factors associated with ST eruption potential were analysed, and the optimal extraction time for nonerupted ST was discussed.

Methods

A retrospective study was performed in a 13,336-participant baseline population aged 3–12 years for whom panoramic radiographs had been obtained in the hospital from 2019 to 2021. The medical records and radiographic data were reviewed to identify patients with ST. Both the demographic variables and ST characteristics were recorded and analysed .

Results

In total, 890 patients with 1,180 ST were screened from the 13,336 baseline population. The ratio of males (679) to females (211) was approximately 3.2:1. Generally, ST occurred singularly and were frequently found in the maxilla (98.1%). A total of 40.8% of ST were erupted, and the 6-year-old age group presented the highest eruption rate (57.8%). The eruption rate of ST was highly negatively correlated with age. A total of 598 patients additionally underwent cone- beam computed tomography (CBCT). According to the CBCT images, the majority of ST were conical, normally oriented, palatally situated, nonerupted and symptomatic. The most common ST-associated complication was failed eruption of adjacent teeth. In addition, symptomatic ST were more common in the 7- to 8- and 9- to 10-year-old age groups. The eruption rate of ST was 25.3% among the patients who had undergone CBCT. A normal orientation and the labial position were significant protective factors for ST eruption, with odds ratios (ORs) of 0.004 (0.000-0.046) and 0.086 (0.007–1.002), respectively. Age and the palatal position were significant risk factors, with ORs of 1.193 (1.065–1.337) and 2.352 (1.377–4.02), respectively.

Conclusions

This study provides a detailed analysis of ST characteristics in 3–12 year old children. Age as well as the position and orientation of ST were reliable predictors of the ST eruption. An age of 6 years old may be the optimal time for extraction of nonerupted ST to maximize the utilization of eruption potential and reduce the incidence of ST-associated complications.
Remote online open book examinations: through the lenses of faculty and students in health professions programmes
Authors: Er Hui Meng , Wong Pei Se , Nadarajah Vishna Devi
Published: June 2023

Background

Open book examinations have been used to assess students’ higher order cognitive skills. These examinations can be conducted online remotely with the advancement of technology. However, there are concerns regarding its validity and reliability particularly if the examinations are not proctored. The objective of this study was to explore the perceptions of faculty and students in health professions programmes about remote online open book examinations (ROOBE).

Methods

Semi-structured interviews were conducted among 22 faculty staff who were involved in ROOBE in health professions programmes. All interviews were audio recorded, transcribed verbatim and analysed using a thematic analysis approach. The perceptions of 249 medical students were obtained using an online questionnaire after they completed ROOBE.

Results

The faculty agreed that open book examinations could promote students’ higher order cognitive skills and reduce students’ stress. However, they were concerned about students’ academic integrity during non-invigilated ROOBE which could affect recognition by accreditation and professional bodies. The shift from traditional practice of closed-book examinations to ROOBE required change management with the support of guidelines and faculty training. 

Majority of the students claimed that the examinations were challenging
as they assessed their ability to apply knowledge in real world problems. Nevertheless, they preferred ROOBE due to less anxiety and memorisation, and
more emphasis on problem solving skills. The shortcomings were insufficient time for information searching during
examinations and uncertainty in preparedness for future practice as they
focused less on memorisation of factual knowledge during examination
preparation. Cheating among peers and
internet instability during non-invigilated ROOBE were the concerns highlighted
by some students.

Conclusions

Faculty and students expressed favourable views about ROOBE in promoting
higher order cognitive skills. Adequate
technological support was essential during ROOBE. While there was a need to
address issues related to academic integrity, ROOBE could be included as an
authentic assessment within the systems of assessment.
Multimodal teaching methods for students in dentistry: a replacement for traditional teaching or a valuable addition? A three-year prospective cohort study
Authors: Gatt Gabriella , Attard Nikolai J.
Published: June 2023

Background

This student-centred prospective cohort study evaluated the impact of multimodal teaching methods on student performance in the theoretical domain of dental studies.

Methods

Dental students answered anonymous questionnaires indicating their preferences and opinions three times over three consecutive academic years. Data collected included gender, course, year of study and most frequent and preferred learning modality. Survey responses from Google Forms were analysed with SPSS 20.0 software (IBM Company, Chicago, IL, USA). Scale responses were tested with the Mann-Whitney U test against gender, program and year of study. Grades obtained from structured examinations held in the third academic year were analysed using the Wilcoxon Signed Rank Test according to the teaching method employed. The level of statistical significance was set at p < 0.05.

Results

The response rate was high (> 80%) throughout the study. Acceptance of online modalities increased over time (Kruskal-Wallis test, p < 0.001) and 75% of students requested that online teaching modalities be maintained. Significant differences in gender, program of study, year of study and discipline taught were observed (Mann-Whitney test, p < 0.05). Females differed from males by favouring online modalities and face-to-face lectures, respectively, and clinical year students opted to retain pre-recorded online lectures. Recorded lectures resulted better for teaching core knowledge (Wilcoxon Signed Rank Test, p = 0.034), while face-to-face lectures were better for teaching applied knowledge (Wilcoxon Signed Rank Test, p = 0.043). Student responses to open-ended questions identified the need for a blended approach with in-person lecturing as an opportunity to socialise and avoid mental health issues. Although preferences varied, students showed a willingness to influence their learning and changes in curriculum, a predilection for self-directed learning and the need for freedom in engaging with resources and content.

Conclusions

In the context of this study, online teaching modalities resulted in comparable examination performance and improved student satisfaction. This highlights the need for a blended approach to teaching.
“Discrimination is always intersectional” – understanding structural racism and teaching intersectionality in medical education in Germany
Authors: Weßel Merle , Gerhards Simon Matteo
Published: June 2023

Background

Racism in medicine represents a global problem. It takes place on the individual, institutional and structural level. Especially structural racism can have serious effects on the health of individual people. Furthermore, racist discrimination is not always based on race solemnly but frequently intersects with other social categories such as gender, class or religion. To describe this multidimensional form of discrimination the term intersectionality has been coined. However, the understanding of structural intersectional racism in medicine is still fragmented, especially in the German context. Yet, medical students need to be trained in understanding structural and intersectional racism to see the impact of racist structures on the patient’s health.

Method

We conducted a qualitative study to explore the knowledge, awareness and perception of racism in medicine and health care of medical students in Germany. Our research questions are how do medical student understand structural racism and its effects on health in Germany? Do students see interrelations with other forms of discrimination and in this context to what extent are they familiar with the concept of intersectionality? Which categories intersect from their point of views with race in context of medicine and health care? We conducted focus groups with medical students (n = 32) in Germany.

Results

Our results demonstrate that students have a wide spectrum of knowledge, awareness and perceptions about racism from being rather elaborate to very little knowledge about it. The students have particular problems to understand and situate structural racism in Germany. Some raised doubts about the relevance. Yet, other students are aware of the concept of intersectionality and are convinced that racism must be looked at from an intersectional perspective.

Conclusions

The diverse knowledge, awareness and perceptions of medical students about structural racism and intersectionality hints to a lack of systematic education of medical students about these issues in Germany. Yet, in context of diversifying societies an understanding about racism and its impact on health is imminent for future medical doctors to provide good care for their patients. Therefore, this knowledge gap must be systematically filled by the medical education.
Curriculum satisfaction of graduates of medical residency in ophthalmology
Authors: Guimarães A.B.C. , Amaral E. , Carvalho K.M.
Published: June 2023

Background

The number of ophthalmologists trained in Brazil has increased, but their satisfaction with the medical residency curriculum is unclear.

The purpose of this study is to evaluate the satisfaction and self-confidence of graduates of a reference ophthalmology residency program in Brazil and to analyze whether there is a difference in these parameters among those who graduated in different decades.

Methods

This is a cross-sectional web-based study conducted in 2022 with 379 ophthalmologists who graduated from the Faculty of Medical Sciences of the State University of Campinas (UNICAMP), Brazil. We aim to obtain data on satisfaction and self-confidence in clinical and surgical practices.

Results

In total, 158 questionnaires were completed (41.68% response rate); 104 respondents completed their medical residency between 2010 and 2022, 34 between 2000 and 2009, and only 20 before 2000. Most respondents were satisfied or very satisfied with their programs (98.7%). Respondents reported insufficient exposure to low vision rehabilitation (62.7%), toric intraocular implants (60.8%), refractive surgery (55.7%), and orbital trauma surgery (84.8%), particularly among graduates before 2010. They also reported insufficient training in certain non-clinical areas, such as office management (61.4%), health insurance management (88.6%), and personnel and administration skills (74.1%). We found that respondents who graduated a long time ago had higher confidence in clinical and surgical practices.

Conclusions

Brazilian ophthalmology residents and UNICAMP graduates expressed high levels of satisfaction with their residency training programs. Those who completed the program a long time ago appear to have more confidence in clinical and surgical practices. There were clinical and non-clinical areas with insufficient training identified for improvement.
Next-generation sequencing in the diagnosis of neurobrucellosis: a case series of eight consecutive patients
Authors: Yu Lili , Zhang Zhenyuan , Zou Yueli , Qi Xuejiao , Zhang Yu , Bai Kaixuan , Han Xiaochen , Bu Hui
Published: June 2023

Background

Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF.

Methods

Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed.

Results

Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1–4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1.

Conclusion

NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice.
Granzyme B + CD8 + T cells with terminal differentiated effector signature determine multiple sclerosis progression
Authors: Shi Ziyan , Wang Xiaofei , Wang Jiancheng , Chen Hongxi , Du Qin , Lang Yanlin , Kong Lingyao , Luo Wenqin , Qiu Yuhan , Zhang Ying , Li Chen , Wen Dingke , Yao Jie , Cheng Xia , Cai Linjun , Lin Xue , Wang Rui , Mou Zichao , Li Shuangjie , Liu Duanya , Zhou Hong , Zhou Hongyu , Yang Mu
Published: June 2023

Background

Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing–remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS.

Methods

Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively.

Results

Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy.

Conclusions

Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS.
A complex network of transcription factors and epigenetic regulators involved in bovine leukemia virus transcriptional regulation
Authors: Plant Estelle , Bellefroid Maxime , Van Lint Carine
Published: June 2023

Bovine Leukemia Virus (BLV) is the etiological agent of enzootic bovine leukosis, a disease characterized by the neoplastic proliferation of B cells in cattle. While most European countries have introduced efficient eradication programs, BLV is still present worldwide and no treatment is available. A major feature of BLV infection is the viral latency, which enables the escape from the host immune system, the maintenance of a persistent infection and ultimately the tumoral development. BLV latency is a multifactorial phenomenon resulting in the silencing of viral genes due to genetic and epigenetic repressions of the viral promoter located in the 5ʹ Long Terminal Repeat (5ʹLTR). However, viral miRNAs and antisense transcripts are expressed from two different proviral regions, respectively the miRNA cluster and the 3ʹLTR. These latter transcripts are expressed despite the viral latency affecting the 5ʹLTR and are increasingly considered to take part in tumoral development. In the present review, we provide a summary of the experimental evidence that has enabled to characterize the molecular mechanisms regulating each of the three BLV transcriptional units, either through cis-regulatory elements or through epigenetic modifications. Additionally, we describe the recently identified BLV miRNAs and antisense transcripts and their implications in BLV-induced tumorigenesis. Finally, we discuss the relevance of BLV as an experimental model for the closely related human T-lymphotropic virus HTLV-1.
Self-locking stand-alone cage versus cage-plate fixation in monosegmental anterior cervical discectomy and fusion with a minimum 2-year follow-up: a systematic review and meta-analysis
Authors: Zhang Yu , Ju Jidong , Wu Jinchun
Published: June 2023

Background

Currently, self-locking stand-alone cages (SSC) are commonly applied in anterior cervical discectomy and fusion (ACDF), as are cage-plate constructs (CPC). However, it remains controversial concerning the long-term effectiveness of both apparatuses. Our purpose is to compare long-term effectiveness of SSC with CPC in monosegmental ACDF.

Methods

Four electronic databases were queried to identify studies comparing SSC versus CPC in monosegmental ACDF. The meta-analysis was carried out with the use of the Stata MP 17.0 software package.

Results

Ten trials with 979 patients were included. Compared to CPC, SSC significantly reduced operative time, intraoperative blood loss, duration of hospitalisation, cervical Cobb angle at final follow-up, 1-month postoperative dysphagia rate, and incidence of adjacent segment degeneration (ASD) at final follow-up. No significant difference was found regarding 1-month postoperative cervical Cobb angle, JOA scores, NDI scores, fusion rate and cage subsidence rate at final follow-up.

Conclusion

Both devices achieved similar long-term effectiveness in monosegmental ACDF regarding JOA scores, NDI scores, fusion rate and cage subsidence rate. SSC had significant advantages over CPC in reducing surgical duration, intraoperative bleeding, duration of hospitalisation, as well as rates of dysphagia and ASD after surgery. Therefore, SSC is a better option than CPC in monosegmental ACDF. However, SSC is inferior to CPC in maintaining cervical curvature at long-term follow-up. Whether radiological changes affect clinical symptoms needs confirmation in trials with longer follow-up.
Dehydroepiandrosterone supplementation and the impact of follicular fluid metabolome and cytokinome profiles in poor ovarian responders
Authors: Viardot-Foucault Veronique , Zhou Jieliang , Bi Dexi , Takinami Yoshihiko , Chan Jerry. K. Y. , Lee Yie Hou
Published: June 2023

Background

Poor ovarian responders (POR) are women undergoing in-vitro fertilization who respond poorly to ovarian stimulation, resulting in the retrieval of lower number of oocytes, and subsequently lower pregnancy rates. The follicular fluid (FF) provides a crucial microenvironment for the proper development of follicles and oocytes through tightly controlled metabolism and cell signaling. Androgens such as dehydroepiandrosterone (DHEA) have been proposed to alter the POR follicular microenvironment, but the impact DHEA imposes on the FF metabolome and cytokine profiles is unknown. Therefore, the objective of this study is to profile and identify metabolomic changes in the FF with DHEA supplementation in POR patients.

Methods

FF samples collected from 52 POR patients who underwent IVF with DHEA supplementation (DHEA +) and without (DHEA-; controls) were analyzed using untargeted liquid chromatography-tandem mass spectrometry (LC–MS/MS) metabolomics and a large-scale multiplex suspension immunoassay covering 65 cytokines, chemokines and growth factors. Multivariate statistical modelling by partial least squares-discriminant regression (PLSR) analysis was performed for revealing metabolome-scale differences. Further, differential metabolite analysis between the two groups was performed by PLSR β-coefficient regression analysis and Student’s t-test.

Results

Untargeted metabolomics identified 118 FF metabolites of diverse chemistries and concentrations which spanned three orders of magnitude. They include metabolic products highly associated with ovarian function – amino acids for regulating pH and osmolarity, lipids such fatty acids and cholesterols for oocyte maturation, and glucocorticoids for ovarian steroidogenesis. Four metabolites, namely, glycerophosphocholine, linoleic acid, progesterone, and valine were significantly lower in DHEA + relative to DHEA- (p < 0.05–0.005). The area under the curves of progesterone glycerophosphocholine, linoleic acid and valine are 0.711, 0.730, 0.785 and 0.818 (p < 0.05–0.01). In DHEA + patients, progesterone positively correlated with IGF-1 (Pearson r: 0.6757, p < 0.01); glycerophosphocholine negatively correlated with AMH (Pearson r: -0.5815; p < 0.05); linoleic acid correlated with estradiol and IGF-1 (Pearson r: 0.7016 and 0.8203, respectively; p < 0.01 for both).

In DHEA- patients, valine negatively correlated with serum-free testosterone (Pearson r: -0.8774; p < 0.0001). Using the large-scale immunoassay of 45 cytokines, we observed significantly lower MCP1, IFNγ, LIF and VEGF-D levels in DHEA + relative to DHEA.

Conclusions

In POR patients, DHEA supplementation altered the FF metabolome and cytokine profile. The identified four FF metabolites that significantly changed with DHEA may provide information for titrating and monitoring individual DHEA supplementation.
One-pot synthesis of fuel precursor from acetoin fermentation broth using ionic liquid-based salting-out extraction system
Authors: Zhang Hanxiao , Li Yan , Zhuang Jing , Dai Jianying , Xiu Zhi-Long , Quan Chunshan
Published: June 2023

Background

The development of biofuels, especially liquid hydrocarbon fuels, has been widely concerned due to the depletion of fossil resources. In order to obtain fuel precursors, the reaction of C–C bond formation is usually carried out with biomass derived ketones/aldehydes as reactants. Acetoin and 2,3-butanediol are two platform chemicals, which are co-existed in fermentation broth and traditionally separated by distillation, and then acetoin could be use as C4 building block to prepare hydrocarbon fuels. In order to mitigate the process complexity, direct aldol condensation reaction of acetoin in fermentation broth was studied in this work.

Results

A one-pot process of product separation and acetoin derivative synthesis was proposed based on salting-out extraction (SOE). Aldol condensation reaction of acetoin and 5-methyl furfural in different SOE systems was compared, and the results showed that the synthesis of C10 fuel precursors and separation of C10 products and 2,3-butanediol from fermentation broth were achieved in one-pot with ethanolammonium butyrate (EOAB) and K2HPO4 as SOE reagents and catalysts. The SOE and reaction conditions such as the concentrations of EOAB and K2HPO4, reaction temperature and time were optimized. When the system was composed of 6 wt% EOAB-44 wt% K2HPO4 and the mixture was stirred for 6 h at 200 rpm, 40 ℃, the yield of C10 products was 80.7%, and 95.5% 2,3-butanediol was distributed to the top EOAB-rich phase. The exploration of reaction mechanism showed that an imine intermediate was rapidly formed and the subsequent C10 product formation was the key step for aldol condensation reaction.

Conclusions

With EOAB and K2HPO4 as SOE reagents and catalysts, one-pot synthesis of fuel precursor from acetoin fermentation broth was achieved without prior purification. A yield of 80.7% for C10 products was obtained which was accumulated at the interface of two aqueous-phase, and 95.5% 2,3-BD was distributed to the top EOAB-rich phase. This work provides a new integration process of product separation and derivative synthesis from fermentation broth based on ionic liquid SOE.

Graphical Abstract
Regression modelling of conditional morphogene expression links and quantifies the impact of growth rate, fitness and macromorphology with protein secretion in Aspergillus niger
Authors: Cairns Timothy C. , de Kanter Tom , Zheng Xiaomei Z. , Zheng Ping , Sun Jibin , Meyer Vera
Published: June 2023

Background

Filamentous fungi are used as industrial cell factories to produce a diverse portfolio of proteins, organic acids, and secondary metabolites in submerged fermentation. Generating optimized strains for maximum product titres relies on a complex interplay of molecular, cellular, morphological, and macromorphological factors that are not yet fully understood.

Results

In this study, we generate six conditional expression mutants in the protein producing ascomyceteAspergillus nigerand use them as tools to reverse engineer factors which impact total secreted protein during submerged growth. By harnessing gene coexpression network data, we bioinformatically predicted six morphology and productivity associated ‘morphogenes’, and placed them under control of a conditional Tet-on gene switch using CRISPR-Cas genome editing. Strains were phenotypically screened on solid and liquid media following titration of morphogene expression, generating quantitative measurements of growth rate, filamentous morphology, response to various abiotic perturbations, Euclidean parameters of submerged macromorphologies, and total secreted protein. These data were built into a multiple linear regression model, which identified radial growth rate and fitness under heat stress as positively correlated with protein titres. In contrast, diameter of submerged pellets and cell wall integrity were negatively associated with productivity. Remarkably, our model predicts over 60% of variation inA. nigersecreted protein titres is dependent on these four variables, suggesting that they play crucial roles in productivity and are high priority processes to be targeted in future engineering programs. Additionally, this study suggestsA. niger dlpAandcrzAgenes are promising new leads for enhancing protein titres during fermentation.

Conclusions

Taken together this study has identified several potential genetic leads for maximizing protein titres, delivered a suite of chassis strains with user controllable macromorphologies during pilot fermentation studies, and has quantified four crucial factors which impact secreted protein titres inA. niger.
Utilizing biologic disease-modifying anti-rheumatic treatment sequences to subphenotype rheumatoid arthritis
Authors: Das Priyam , Weisenfeld Dana , Dahal Kumar , De Debsurya , Feathers Vivi , Coblyn Jonathan S. , Weinblatt Michael E. , Shadick Nancy A. , Cai Tianxi , Liao Katherine P.
Published: June 2023

Background

Many patients with rheumatoid arthritis (RA) require a trial of multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) to control their disease. With the availability of several bDMARD options, the history of bDMARDs may provide an alternative approach to understanding subphenotypes of RA. The objective of this study was to determine whether there exist distinct clusters of RA patients based on bDMARD prescription history to subphenotype RA.

Methods

We studied patients from a validated electronic health record-based RA cohort with data from January 1, 2008, through July 31, 2019; all subjects prescribed ≥ 1 bDMARD or targeted synthetic (ts) DMARD were included. To determine whether subjects had similar b/tsDMARD sequences, the sequences were considered as a Markov chain over the state-space of 5 classes of b/tsDMARDs. The maximum likelihood estimator (MLE)-based approach was used to estimate the Markov chain parameters to determine the clusters. The EHR data of study subjects were further linked with a registry containing prospectively collected data for RA disease activity, i.e., clinical disease activity index (CDAI). As a proof of concept, we tested whether the clusters derived from b/tsDMARD sequences correlated with clinical measures, specifically differing trajectories of CDAI.

Results

We studied 2172 RA subjects, mean age 52 years, RA duration 3.4 years, and 62% seropositive. We observed 550 unique b/tsDMARD sequences and identified 4 main clusters: (1) TNFi persisters (65.7%), (2) TNFi and abatacept therapy (8.0%), (3) on rituximab or multiple b/tsDMARDs (12.7%), (4) prescribed multiple therapies with tocilizumab predominant (13.6%). Compared to the other groups, TNFi persisters had the most favorable trajectory of CDAI over time.

Conclusion

We observed that RA subjects can be clustered based on the sequence of b/tsDMARD prescriptions over time and that the clusters were correlated with differing trajectories of disease activity over time. This study highlights an alternative approach to consider subphenotyping of patients with RA for studies aimed at understanding treatment response.
Real-time Remote Expert-guided Echocardiography by Medical Students
Authors: Solvin Håvard , Lippert Matthias , Holmstrøm Henrik , Elle Ole Jakob , Brun Henrik
Published: June 2023

Background

Echocardiography is a highly specialised examination performed by experienced healthcare professionals. These experienced healthcare professionals may not be available to patients during all hours in rural healthcare facilities. Remote-guided echocardiography could improve the availability of specialised care for patients living in rural areas. This study examined the feasibility of real-time remote guidance for medical students to perform an echocardiographic assessment of the left side of the heart. Thirteen healthy volunteers were recruited for remote-guided echocardiography, which was performed by 13 medical students. Student examinations/images were compared to reference echocardiography. Measurements of left ventricular fractional shortening and mitral valve blood flow velocity were also compared. Furthermore, guidance through a smartphone videoconference was compared to designated remote guidance software.

Results

Two-thirds of the images acquired by students were rated as medium or good quality and usable to evaluate two thirds of the cardiac structures. No significant bias was found for left ventricular fractional shortening. The measurements from the students’ exams had a variation coefficient of 14.8% compared to the reference. The calculated deviation of the insonation angle was above 25° for both E and A-wave mitral valve blood flow velocity measurements. Images acquired by guidance through smartphone videoconference were of lower quality than those obtained using the designated remote guidance software.

Conclusion

Real-time remote-guided echocardiography performed by medical students has limited value for clinical screening but could be useful for educational purposes.

Graphical Abstract
PHDs-seq: a large-scale phenotypic screening method for drug discovery through parallel multi-readout quantification
Authors: Li Jun , Chi Jun , Yang Yang , Song Zhongya , Yang Yong , Zhou Xin , Liu Yang , Zhao Yang
Published: June 2023

High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.