bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome profiling reveals the genes involved in tuberous root expansion in Pueraria (Pueraria montana var. thomsonii)
Authors: Xufeng Xiao , Yuanfeng Hu , Ming Zhang , Shucheng Si , Haonan Zhou , Weifeng Zhu , Fei Ge , Caijun Wu , Shuying Fan
Published: June 2023

Background

Pueraria is a dry root commonly used in Traditional Chinese Medicine or as food and fodder, and tuberous root expansion is an important agronomic characteristic that influences its yield. However, no specific genes regulating tuberous root expansion in Pueraria have been identified. Therefore, we aimed to explore the expansion mechanism of Pueraria at six developmental stages (P1–P6), by profiling the tuberous roots of an annual local variety “Gange No.1” harvested at 105, 135, 165, 195, 225, and 255 days after transplanting.

Results

Observations of the tuberous root phenotype and cell microstructural morphology revealed that the P3 stage was a critical boundary point in the expansion process, which was preceded by a thickening diameter and yield gain rapidly of the tuberous roots, and followed by longitudinal elongation at both ends. A total of 17,441 differentially expressed genes (DEGs) were identified by comparing the P1 stage (unexpanded) against the P2–P6 stages (expanded) using transcriptome sequencing; 386 differential genes were shared across the six developmental stages. KEGG pathway enrichment analysis showed that the DEGs shared by P1 and P2–P6 stages were mainly involved in pathways related to the “cell wall and cell cycle”, “plant hormone signal transduction”, “sucrose and starch metabolism”, and “transcription factor (TF)”. The finding is consistent with the physiological data collected on changes in sugar, starch, and hormone contents. In addition, TFs including bHLHs, AP2s, ERFs, MYBs, WRKYs, and bZIPs were involved in cell differentiation, division, and expansion, which may relate to tuberous root expansion. The combination of KEGG and trend analyses revealed six essential candidate genes involved in tuberous root expansion; of them, CDC48, ARF, and EXP genes were significantly upregulated during tuberous root expansion while INV, EXT, and XTH genes were significantly downregulated.

Conclusion

Our findings provide new insights into the complex mechanisms of tuberous root expansion in Pueraria and candidate target genes, which can aid in increasing Pueraria yield.
Hospital disaster preparedness in sub-Saharan Africa: a systematic review of English literature
Authors: Farah Bashir , Pavlova Milena , Groot Wim
Published: June 2023

Background

Disasters are increasing worldwide, with Sub-Saharan Africa (SSA) being one of the most prone regions. Hospitals play a key role in disasters. This study provides a systematic review of the evidence on disaster preparedness by hospitals in SSA countries based on English literature.

Methods

A systematic literature review was conducted of articles published between January 2012 and July 2022. We searched PubMed, Elsevier, Science Direct, Google Scholar, the WHO depository library and CDC sites for English language publications. The key inclusion criteria were: publications should have been published in the above period, deal with hospital disaster preparedness in SSA, the full paper should have been available, and studies should have presented a comparison between hospitals and/or a single hospital.

Results

Results indicate improvements in disaster preparedness over time. However, health systems in SSA are generally considered vulnerable, and they find it difficult to adapt to changing health conditions. Inadequately skilled healthcare professionals, underfunding, poor knowledge, the absence of governance and leadership, lack of transparency and bureaucracy are the main preparedness barriers. Some countries are in an infancy stage of their health system development, while others are among the least developed health system in the world. Finally, a major barrier to disaster preparedness in SSA countries is the inability to collaborate in disaster response.

Conclusions

Hospital disaster preparedness is vulnerable in SSA countries. Thus, improvement of hospital disaster preparedness is highly needed.
Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events
Authors: Dunn David T. , Stirrup Oliver T. , McCormack Sheena , Glidden David V.
Published: June 2023

Active-control trials, where an experimental treatment is compared with an established treatment, are performed when the inclusion of a placebo control group is deemed to be unethical. For time-to-event outcomes, the primary estimand is usually the rate ratio, or the closely-related hazard ratio, comparing the experimental group with the control group. In this article we describe major problems in the interpretation of this estimand, using examples from COVID-19 vaccine and HIV pre-exposure prophylaxis trials. In particular, when the control treatment is highly effective, the rate ratio may indicate that the experimental treatment is clearly statistically inferior even when it is worthwhile from a public health perspective. We argue that it is crucially important to consider averted events as well as observed events in the interpretation of active-control trials. An alternative metric that incorporates this information, the averted events ratio, is proposed and exemplified. Its interpretation is simple and conceptually appealing, namely the proportion of events that would be averted by using the experimental treatment rather than the control treatment. The averted events ratio cannot be directly estimated from the active-control trial, and requires an additional assumption about either: (a) the incidence that would have been observed in a hypothetical placebo arm (the counterfactual incidence) or (b) the efficacy of the control treatment (relative to no treatment) that pertained in the active-control trial. Although estimation of these parameters is not straightforward, this must be attempted in order to draw rational inferences. To date, this method has been applied only within HIV prevention research, but has wider applicability to treatment trials and other disease areas.
Dengue hemorrhagic fever with bleeding and fluid overload in a patient with active lupus nephritis: a case report of diagnostic and therapeutic challenges
Authors: Vidanapathirana Manudi , Atukorala Inoshi
Published: June 2023

Background

Diagnosis and management of dengue hemorrhagic fever (DHF) can be challenging in the presence of confounding comorbidities. Important confounders are conditions that alter hematological parameters and intra/extra vascular fluid distribution. We report the case of a patient with active lupus nephritis, who developed DHF with subsequent bleeding and fluid overload. This is the first case report to highlight a unique set of diagnostic and therapeutic challenges in DHF in this context.

Case presentation

A seventeen-year-old girl with lupus nephritis class IV developed a renal flare of lupus and subsequently developed DHF with bleeding per vaginum. Due to acute kidney injury, she was managed with a restrictive fluid approach during the ascending limb with blood transfusion when required, and close monitoring for hemodynamic instability. During the descending limb, hourly input was transiently increased due to a rise in hematocrit. This precipitated nephrogenic pulmonary edema, which was managed with mechanical ventilation and continuous renal replacement therapy.

Conclusions

This patient posed two diagnostic challenges: diagnosis of dengue in a patient with lupus-related bicytopenia, and diagnosis of dengue leakage in a patient with nephrotic syndrome-related ascites. There were three therapeutic difficulties: deciding the fluid quota for DHF in the presence of renal impairment, and balancing the risks and benefits of steroids and anticoagulation in lupus nephritis with dengue. As decisions in such instances are patient-specific, sharing of individual experiences will help guide management decisions.
Epilepsy as the symptom of a spinocerebellar ataxia 13 in a patient presenting with a mutation in the KCNC3 gene
Authors: Li Shao , Shang Dandan , Du Yanjiao , Li Yan , Liu Ruihua
Published: June 2023

Background

The spinocerebellar ataxias (SCAs) refer to a diverse group of neurodegenerative illnesses that vary clinically and genetically. One of the rare subtypes within this group is SCA13, caused by mutations in the KCNC3 gene. Currently, the prevalence of SCA13 remains uncertain, with only a couple of cases being documented in the Chinese population. This study presented a case study of SCA13, where the patient exhibited clinical symptoms of epilepsy and ataxia. The confirmation of the diagnosis was done through Whole Exome Sequncing.

Case presentation

Since childhood, the seventeen-year-old patient has not been capable of participating in numerous sporting activities and has experienced multiple episodes of unconsciousness within the last two years. The neurological evaluation showed a lack of coordination in the lower limbs. Cerebellar atrophy was detected through brain magnetic resonance imaging (MRI). The patient’s gene detection results showed that they exhibit a heterozygous c.1268G > A mutation in the KCNC3 gene located at chr19:50826942. Antiepileptic treatment was promptly administered to the patient, and as a result, her epileptic seizures were resolved quickly. She has since remained free of seizures. After a one-year follow-up, there was no apparent improvement in the patient’s health status except seizure free, which may have worsened.

Conclusion

The case study highlights the importance of actively combining cranial MRI with genetic detection in patients with ataxia of no known cause, particularly in children and young patients, to establish an possibly obvious detection. Patients who are young and have ataxia that is first accompanied by extrapyramidal and epilepsy syndromes should be aware of the potential of having SCA13.
Quality of vision after myopic refractive surgeries: SMILE, FS-LASIK, and ICL
Authors: Du Huiyi , Zhang Bo , Wang Zheng , Xiong Lu
Published: June 2023

Background

To characterize the quality of vision after SMILE, FS-LASIK, and ICL implantation and evaluate the related factors.

Methods

131 eyes of 131 myopic patients (90 female, 41 male) who underwent refractive surgeries including SMILE (35 patients), FS-LASIK (73 patients), and ICL implantation (23 patients) were analyzed. The Quality of Vision questionnaires were completed 3 months after surgery, and the results were characterized and analyzed with baseline characteristics, treatment parameters, and postoperative refractive outcomes using logistic regression analysis to find out predicted factors.

Results

Mean age was 26.5 ± 4.6 years (range: 18 to 39 years) and mean preoperative spherical equivalent was − 4.95 ± 2.04 diopters (D) (range: -1.5 to -13.5). Safety and efficacy index was comparable between different techniques: the safety index was 1.21 ± 0.18, 1.22 ± 0.18, and 1.22 ± 0.16 and the efficacy index were 1.18 ± 0.20, 1.15 ± 0.17, 1.17 ± 0.15 for SMILE, FS-LASIK and ICL respectively. The mean overall QoV score was 13.40 ± 9.11, with mean frequency, severity, and bothersome score of 5.40 ± 3.29, 4.53 ± 3.04, and 3.48 ± 3.18 respectively, and there was no significant difference between different techniques. Overall, the symptom with the highest scores was glare, following fluctuation in vision and halos. Only the scores of halos were significantly different among different techniques (P < 0.000). Using ordinal regression analysis, mesopic pupil size was identified as a risk factor (OR = 1.63, P = 0.037), while postoperative UDVA was a protective factor (OR = 0.036, P = 0.037) for overall QoV scores. Using binary logistic regression analysis, we found that patients with larger mesopic pupil size had an increased risk to experience glare postoperatively; compared to ICL, patients who underwent SMILE or FS-LASIK tended to report fewer halos; patients with better postoperative UDVA were less likely to report blurred vision and focusing difficulty; with larger residual myopic sphere postoperatively, patients experienced focusing difficulties and difficulty judging distance or depth perception more frequently.

Conclusions

SMILE, FS-LASIK, and ICL had comparable visual outcomes. Overall, glare, fluctuation in vision, and halos were the most frequently experienced visual symptoms 3 months postoperatively. Patients with ICL implanted tended to report halos more frequently compared with SMILE and FS-LASIK. Mesopic pupil size, postoperative UDVA, and postoperative residual myopic sphere were predicted factors for reported visual symptoms.
Abnormal blood lipid and electrocardiogram characteristics in common mental disorders
Authors: Li Yan , Tang Chaohua , Wu Weibo , Li Zhijian , Li Xuesong , Huang Wei , Chen Wensheng , Mai Xiancong , Li Xiaoling , Xu Caixia , Xie Guojun , Liang Jiaquan
Published: June 2023

Background

At present, there is not enough evidence to prove the relationship between blood lipid and electrocardiogram (ECG) abnormalities in common mental disorders (CMD). This study aimed to explore the relationship between them, to detect and prevent arrhythmia or sudden death.

Methods

We collected 272 CMD patients (maintained a fixed drug dose pattern for 1 year or more), including 95 schizophrenias (SC), 90 bipolar disorders (BD) and 87 major depressive disorders (MDD), and 78 healthy controls (HC) from the Third People’s Hospital of Foshan, China. We analyzed and compared their blood lipid and ECG indicators, to clarify the relationship between them.

Results

350 participants were included. There were no significant differences in age, gender, total cholesterol (TC), low density lipoprotein (LDL) and QTc (p > 0.05) among subjects. And there were significant differences in body mass index (BMI), triglyceride (TG), high density lipoprotein (HDL), heart rate, PR interval and QRS width (p < 0.05). Person correlation analysis showed that QRS width was positively correlated with BMI and TG. And negatively correlated with HDL. Meanwhile, QTc was positively correlated with BMI. Multiple linear regional analysis further proved that TG (B = 3.849, p = 0.007) and LDL (B = 11.764, p = 0.018) were the risk factors, and HDL (B = -9.935, p = 0.025) was the protective factor for QRS width increase.

Conclusion

Long term medication of CMD patients should strengthen weight management, and conduct regular blood lipid and ECG examinations to achieve early detection and intervention in order to promote their health.
Emergency surgery of intra-articular calcaneal fractures using sinus tarsi approach with modified reduction technique
Authors: Hu Yanwen , Chen Lucheng , Qian Yaxing , Wu Junjie , Xu Hao
Published: June 2023

Background

The purpose of this study was to evaluate emergency surgery of calcaneal fractures using the sinus tarsi approach (STA) with modified reduction technique in terms of complication rates, iconography results and functional outcome.

Methods

We evaluated the outcomes of 26 patients treated in an emergency using STA with modified reduction technique. For that, we assessed Böhler´s angle, Gissane angle, reduction of the calcaneal body, and posterior facet, the visual analog scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, complications, preoperative time, operative time, and in-hospital time.

Results

Recovery of calcaneal anatomy and articular surface were found at final follow-up. The mean Böhler´s angle at final follow-up were 30.68° ± 3.69°, of which was 15.02° ± 3.88° preoperatively (p < 0.001). The mean Gissane angle at final follow-up were 114.54° ± 11.16° of which was 88.86° ±10.96° preoperatively (p < 0.001). All cases had the varus/valgus angle of the tuber within 5 degrees. At the final follow-up, the mean AOFAS score was 89.23 ± 4.63, and the VAS score was 22.73 ± 6.5.

Conclusions

Emergency surgery using STA with modified reduction technique is reliable, effective, and safe for treatment of calcaneal fractures. This technique can bring good clinical outcomes and a low rate of wound complications, reducing the in-hospital time, costs, and accelerating rehabilitation.
Duodenal microbiota and weight-loss following sleeve gastrectomy and Roux-en-Y gastric bypass – a pilot study
Authors: Stefura Tomasz , Rusinek Jakub , Zając Maciej , Zapała Barbara , Gosiewski Tomasz , Sroka-Oleksiak Agnieszka , Salamon Dominika , Pędziwiatr Michał , Major Piotr
Published: June 2023

Background

Bariatric surgery is the most effective method of morbid obesity treatment. Microbiota has many functions in human body and many of them remain to be unknown. The aim of this study was to establish if the composition of duodenal microbiota influences success rate of bariatric surgery.

Methods

It was a prospective cohort study. The data concerning demographics and comorbidities was collected perioperatively. The duodenal biopsies were collected prior to surgery with the gastroscope. Then DNA analysis was conducted. The data connected to the operation outcomes was gathered after 6 and 12 months after surgery.

Results

Overall, 32 patients were included and divided into two groups (successful – group 1 and unsuccessful – group 0) based on percentage excess weight loss after 6 months were created. The Total Actual Abundance was higher in group 0. In group 0 there was a significantly higher amount of Roseburia and Arthrobacter (p = 0.024, p = 0.027, respectively). Genus LDA effect size analysis showed Prevotella, Megasphaera and Pseudorhodobacter in group 1 to be significant. Whereas abundance of Roseburia and Arthrobacter were significant in group 0.

Conclusions

Duodenal microbiota composition may be a prognostic factor for the success of the bariatric surgery but further research on the larger group is needed.
Impact of corticosteroid administration on the response of exposed dental pulp to capping with bioactive cements-experimental study on mongrel dogs
Authors: Soliman Hanan A. , EL-Toukhy Radwa Ibrahim , Ibrahim Mona Mohsen Abdo , Grawish Mohammed E. , kader Sobh Mohamed Abdel , Mahmoud Salah Hasab
Published: June 2023

Background

Corticosteroids are commonly used as a treatment for a variety of pathological conditions, however, systemic corticosteroid administration has adverse effects including impaired immune response and wound healing. Such complications may affect pulp healing after direct pulp capping. The current study evaluated the influence of corticosteroids on the healing ability of exposed dogs’ dental pulps after direct pulp capping (DPC) with bioactive materials.

Methods

Ten healthy male dogs were assigned randomly into two groups, 5 dogs each: group I represent the control group which did not receive any medication, and group II was given corticosteroid for 45 days before DPC and till the dogs were euthanized (n = 75 teeth for each group). Following mechanical exposure, the pulps were randomly capped with either Ca(OH)2, MTA, or Biodentine. The pulpal tissues’ reaction to the capping materials was evaluated 65 days postoperatively according to the following parameters: calcific bridge formation, pulpal inflammation, pulp necrosis, and bacterial infiltration.

Results

The corticosteroid-treated group revealed no significant difference compared to the control group concerning the pulp healing response (P > 0.05). Both Biodentine and MTA-treated specimens revealed significant differences with Ca(OH)2-treated specimens (P < 0.05) which displayed a superior positive effect of both MTA and Biodentine to Ca(OH)2 regarding all the parameters.

Conclusions

Direct pulp capping technique whenever indicated in subjects treated with corticosteroid immunosuppressive drugs like prednisone performed well in aseptic conditions especially when capped with bioactive materials.
Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths
Authors: Gijsbers J. C. , Englebert N. , Prata K. E. , Pichon M. , Dinesen Z. , Brunner R. , Eyal G. , González-Zapata F. L. , Kahng S. E. , Latijnhouwers K. R. W. , Muir P. , Radice V. Z. , Sánchez J. A. , Vermeij M. J. A. , Hoegh-Guldberg O. , Jacobs S. J. , Bongaerts P.
Published: June 2023

Background

Mesophotic coral communities are increasingly gaining attention for the unique biological diversity they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies on corals have rarely included mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers.

Results

Here, we used reduced-representation genome sequencing to conduct a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed deep divergences within the two genera and undescribed diversity across the current taxonomic species. Five of the eight focal species consisted of at least two sympatric and genetically distinct lineages, which were consistently detected across different methods.

Conclusions

The repeated observation of genetically divergent lineages associated with mesophotic depths highlights that there may be many more mesophotic-specialist coral species than currently acknowledged and that an urgent assessment of this largely unstudied biological diversity is warranted.
Associations between DNA methylation and gene regulation depend on chromatin accessibility during transgenerational plasticity
Authors: Bogan Samuel N. , Strader Marie E. , Hofmann Gretchen E.
Published: June 2023

Background

Epigenetic processes are proposed to be a mechanism regulating gene expression during phenotypic plasticity. However, environmentally induced changes in DNA methylation exhibit little-to-no association with differential gene expression in metazoans at a transcriptome-wide level. It remains unexplored whether associations between environmentally induced differential methylation and expression are contingent upon other epigenomic processes such as chromatin accessibility. We quantified methylation and gene expression in larvae of the purple sea urchin Strongylocentrotus purpuratus exposed to different ecologically relevant conditions during gametogenesis (maternal conditioning) and modeled changes in gene expression and splicing resulting from maternal conditioning as functions of differential methylation, incorporating covariates for genomic features and chromatin accessibility. We detected significant interactions between differential methylation, chromatin accessibility, and genic feature type associated with differential expression and splicing.

Results

Differential gene body methylation had significantly stronger effects on expression among genes with poorly accessible transcriptional start sites while baseline transcript abundance influenced the direction of this effect. Transcriptional responses to maternal conditioning were 4–13 × more likely when accounting for interactions between methylation and chromatin accessibility, demonstrating that the relationship between differential methylation and gene regulation is partially explained by chromatin state.

Conclusions

DNA methylation likely possesses multiple associations with gene regulation during transgenerational plasticity in S. purpuratus and potentially other metazoans, but its effects are dependent on chromatin accessibility and underlying genic features.
Postural stability measures in healthy miniature Dachshunds obtained using a pressure mat and a force platform: a validity and reliability study
Authors: Shaheen Aliah F. , Lins Daniela , Toledo Thais , Gómez Álvarez Constanza B.
Published: June 2023

Background

Miniature Dachshunds have a high prevalence of neurological and musculoskeletal diseases potentially affecting their balance. The postural stability of dogs in quiet standing is an indicator of postural control and can aid in diagnosing and monitoring lameness and other pathologies affecting balance. Measures of centre of pressure (CoP) can be obtained from force and pressure platform systems to evaluate postural stability, however the two systems have not been compared and the latter has not been validated in dogs. The aims of this study were to assess the validity and reliability of using a pressure mat compared to a force platform and report normative values of CoP measures in healthy miniature Dachshunds. Forty two healthy miniature Dachshunds of smooth, long and wire-haired breed types stood still on a pressure mat (Tekscan MatScan®) placed on a force platform and the two systems were synchronised. Maximum anterior-posterior (AP) and medial-lateral (ML) ranges, sway path and 95% area of a best-fit ellipse were computed. Bland-Altman plots and coefficients of correlation assessed validity; intra-class correlation coefficients (ICC) assessed inter-test reliability for both systems. Non-linear regression analyses were used to describe the relationship between CoP and demographic measures.

Results

Strong correlations for AP range, ML range and 95% ellipse area and moderate correlation for sway path were found between the two devices. ICC showed good reliability (0.75–0.90) for AP range and moderate (0.5–0.75) for ML range and the 95% ellipse area for both devices. Sway path reliability was excellent (> 0.90) with the force platform but moderate with the pressure mat. Age was positively correlated with balance (inversely correlated with all measures except sway path), while weight explained 94% (force platform) and 27% (pressure mat) of the variance in sway path.

Conclusions

Pressure mats can be used to obtain valid and reliable measures of CoP and replace use of force platforms. Older (non-senior) and heavier (non-obese) dogs show better postural stability. Clinical examinations should include the use of a range of CoP measures when assessing postural balance, while accounting for the effects of age and body weight.
A novel variant of the SOX10 gene associated with Waardenburg syndrome type IV
Authors: Wang Yanan , Chai Yuqiong , Zhang Pai , Zang Weiwei
Published: June 2023

Background

Waardenburg syndrome (WS) is a rare genetic disorder characterized by varying degrees of sensorineural hearing loss and accumulated pigmentation in the skin, hair and iris. The syndrome is classified into four types (WS1, WS2, WS3, and WS4), each with different clinical phenotypes and underlying genetic causes. The aim of this study was to identify the pathogenic variant in a Chinese family with Waardenburg syndrome type IV.

Methods

The patient and his parents underwent a thorough medical examination. We applied whole exome sequencing to identify the causal variant on the patient and other family members.

Results

The patient presented with iris pigmentary abnormality, congenital megacolon and sensorineural hearing loss. The clinical diagnosis of the patient was WS4. The whole exome sequencing (WES) revealed a novel variant (c.452_456dup) in the SOX10 gene, which could be responsible for the observed pathogenic of WS4 in this patient. Our analysis suggests that this variant produces a truncated protein that contributes to the development of the disease. The genetic test confirmed the diagnosis of WS4 in the patient from the studied pedigree.

Conclusions

This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS4. The newly identified SOX10 gene variant can expand the understanding of WS4.
Assessing the implementation of physical activity-promoting public policies in the Republic of Ireland: a study using the Physical Activity Environment Policy Index (PA-EPI)
Authors: Volf Kevin , Kelly Liam , Van Hoye Aurelie , García Bengoechea Enrique , MacPhail Ann , Woods Catherine B. ,   The PEN Consortium
Published: June 2023

Background

Government policy can promote physical activity (PA) as part of a multilevel systems-based approach. The Physical Activity Environment Policy Index (PA-EPI) is a monitoring framework which assesses the implementation of government policy by drawing on the experience of national stakeholders. This study is the first to assess the extent of policy implementation in the Republic of Ireland using the PA-EPI tool, and to provide information on how policy implementation can be improved, with the intention of maximizing its impact on population levels of PA.

Methods

This mixed-methods research study, comprising eight steps, was carried out in 2022. Information documenting the evidence for implementation of PA policy, across all 45 PA-EPI indicators, was collected via systematic document analysis, and validated via survey and interview with government officials. Thirty-two nongovernment stakeholders rated this evidence on a five-point Likert scale. Aggregated scores were reviewed by stakeholders who collectively identified and prioritized critical implementation gaps.

Results

Of the 45 PA-EPI indicators, one received an implementation rating of ‘none/very little’, 25 received a rating of ‘low’ and 19 received a ‘medium’ rating. No indicator was rated as fully implemented. The indicators that received the highest level of implementation related to sustained mass media campaigns promoting PA and PA monitoring. Ten priority recommendations were developed.

Conclusions

This study reveals substantial implementation gaps for PA policy in the Republic of Ireland. It provides recommendations for policy action to address these gaps. In time, studies utilizing the PA-EPI will enable cross-country comparison and benchmarking of PA policy implementation, incentivizing improved PA policy creation and implementation.
Biomechanical properties of different anterior and posterior techniques for atlantoaxial fixation: a finite element analysis
Authors: Li Jie , Cao Shuai , Guo Dong , Lu Teng , Zang Quanjin
Published: June 2023

Background

Many techniques for atlantoaxial fixation have been developed. However, the biomechanical differences among various atlantoaxial fixation methods remain unclear. This study aimed to evaluate the biomechanical influence of anterior and posterior atlantoaxial fixation techniques on fixed and nonfixed segments.

Methods

An occiput-C7 cervical finite element model was used to construct 6 surgical models including a Harms plate, a transoral atlantoaxial reduction plate (TARP), an anterior transarticular screw (ATS), a Magerl screw, a posterior screw-plate, and a screw-rod system. Range of motion (ROM), facet joint force (FJF), disc stress, screw stress, and bone-screw interface stress were calculated.

Results

The C1/2 ROMs were relatively small in the ATS and Magerl screw models under all loading directions except for extension (0.1°–1.0°). The posterior screw-plate system and screw-rod system generated greater stresses on the screws (77.6–1018.1 MPa) and bone-screw interfaces (58.3–499.0 MPa). The Harms plate and TARP models had relatively small ROMs (3.2°–17.6°), disc stress (1.3–7.6 MPa), and FJF (3.3–106.8 N) at the nonfixed segments. Changes in disc stress and FJF of the cervical segments were not consistent with changes in ROM.

Conclusions

ATS and Magerl screws may provide good atlantoaxial stability. The posterior screw-rod system and screw-plate system may have higher risks of screw loosening and breakage. The Harms plate and TARP model may more effectively relieve nonfixed segment degeneration than other techniques. The C0/1 or C2/3 segment may not be more susceptible to degeneration than other nonfixed segments after C1/2 fixation.
Ultrasound guided versus blinded injection in trigger finger treatment: a prospective controlled study
Authors: Tunçez Mahmut , Turan Kaya , Aydın Özgür Doğan , Çetin Tunçez Hülya
Published: June 2023

Background

Trigger finger is a common disease with a lifetime prevalence of 2%. One of the frequently preferred non-surgical treatments is blinded injection around the A1 pulley. This study aims to compare the clinical results of ultrasound-guided and blinded corticosteroid injection in the trigger finger.

Methods

In this prospective clinical study, 66 patients who had persistent symptoms of a single trigger finger were included. Patients with similar baseline characteristics such as age, gender, triggering period, and comorbidities were randomized. 34 patients had ultrasound-guided (UG), and 32 had blinded injections (BG). QDASH, VAS, time to return to work, and complications were compared between the groups.

Results

The mean age was 52,66 (29–73) years. There were 18 male and 48 female patients. In the UG, the triggering resolved faster, returning to work was earlier, and the medication period was shorter (p < 0.05). A total of 17 patients who had diabetes mellitus received re-injections, 11 of which were in BG and 6 in UG (p < 0.05). Although statistically significantly lower scores were obtained in UG at the 1st and 4th weeks in the QDASH and VAS scores (p < 0.05), at the 12th and 24 weeks, there was no significant difference (p > 0.05).

Conclusion

Using ultrasound guidance for corticosteroid injections is more effective for treating trigger fingers than the blinded method, leading to better results and a faster return to work in the early stages of treatment.
Real-world evidence in achondroplasia: considerations for a standardized data set
Authors: Alanay Yasemin , Mohnike Klaus , Nilsson Ola , Alves Inês , AlSayed Moeenaldeen , Appelman-Dijkstra Natasha M. , Baujat Genevieve , Ben-Omran Tawfeg , Breyer Sandra , Cormier-Daire Valerie , Gregersen Pernille Axél , Guillén-Navarro Encarna , Högler Wolfgang , Maghnie Mohamad , Mukherjee Swati , Cohen Shelda , Pimenta Jeanne , Selicorni Angelo , Semler J. Oliver , Sigaudy Sabine , Popkov Dmitry , Sabir Ian , Noval Susana , Sessa Marco , Irving Melita
Published: June 2023

Background

Collection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability, accessibility, interoperability, and reuse of digital assets, and that captures long-term, high-quality data, would improve understanding of the natural history of achondroplasia, quality of life, and related outcomes.

Methods

The Europe, Middle East, and Africa (EMEA) Achondroplasia Steering Committee comprises a multidisciplinary team of 17 clinical experts and 3 advocacy organization representatives. The committee undertook an exercise to identify essential data elements for a standardized prospective registry to study the natural history of achondroplasia and related outcomes.

Results

A range of RWE on achondroplasia is being collected at EMEA centres. Whereas commonalities exist, the data elements, methods used to collect and store them, and frequency of collection vary. The topics considered most important for collection were auxological measures, sleep studies, quality of life, and neurological manifestations. Data considered essential for a prospective registry were grouped into six categories: demographics; diagnosis and patient measurements; medical issues; investigations and surgical events; medications; and outcomes possibly associated with achondroplasia treatments.

Conclusions

Long-term, high-quality data are needed for this rare, multifaceted condition. Establishing registries that collect predefined data elements across age spans will provide contemporaneous prospective and longitudinal information and will be useful to improve clinical decision-making and management. It should be feasible to collect a minimum dataset with the flexibility to include country-specific criteria and pool data across countries to examine clinical outcomes associated with achondroplasia and different therapeutic approaches.
The association of hypoglycemia with outcome of critically ill children in relation to nutritional and blood glucose control strategies
Authors: Gunst Jan , De Bruyn Astrid , Jacobs An , Langouche Lies , Derese Inge , Dulfer Karolijn , Güiza Fabian , Garcia Guerra Gonzalo , Wouters Pieter J. , Joosten Koen F. , Verbruggen Sascha C. , Vanhorebeek Ilse , Van den Berghe Greet
Published: June 2023

Background

Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol.

Methods

In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia.

Results

Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia.

Conclusion

Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia.
Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1
Authors: Atreya Mihir R. , Cvijanovich Natalie Z. , Fitzgerald Julie C. , Weiss Scott L. , Bigham Michael T. , Jain Parag N. , Schwarz Adam J. , Lutfi Riad , Nowak Jeffrey , Allen Geoffrey L. , Thomas Neal J. , Grunwell Jocelyn R. , Baines Torrey , Quasney Michael , Haileselassie Bereketeab , Alder Matthew N. , Lahni Patrick , Ripberger Scarlett , Ekunwe Adesuwa , Campbell Kyle R. , Walley Keith R. , Standage Stephen W.
Published: June 2023

Background

Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults. In contrast, we have previously demonstrated higher mortality in the juvenile host. Given the potential pleiotropic effects of PCSK9 on the endothelium, beyond canonical effects on serum lipoproteins, both of which may influence sepsis outcomes, we sought to test the influence of PCSK9 LOF genotype on endothelial dysfunction.

Methods

Secondary analyses of a prospective observational cohort of pediatric septic shock. Genetic variants of PCSK9 and LDLR genes, serum PCSK9, and lipoprotein concentrations were determined previously. Endothelial dysfunction markers were measured in day 1 serum. We conducted multivariable linear regression to test the influence of PCSK9 LOF genotype on endothelial markers, adjusted for age, complicated course, and low- and high-density lipoproteins (LDL and HDL). Causal mediation analyses to test impact of select endothelial markers on the association between PCSK9 LOF genotype and mortality. Juvenile Pcsk9 null and wildtype mice were subject to cecal slurry sepsis and endothelial markers were quantified.

Results

A total of 474 patients were included. PCSK9 LOF was associated with several markers of endothelial dysfunction, with strengthening of associations after exclusion of those homozygous for the rs688 LDLR variant that renders it insensitive to PCSK9. Serum PCSK9 was not correlated with endothelial dysfunction. PCSK9 LOF influenced concentrations of Angiopoietin-1 (Angpt-1) upon adjusting for potential confounders including lipoprotein concentrations, with false discovery adjusted p value of 0.042 and 0.013 for models that included LDL and HDL, respectively. Causal mediation analysis demonstrated that the effect of PCSK9 LOF on mortality was mediated by Angpt-1 (p = 0.0008). Murine data corroborated these results with lower Angpt-1 and higher soluble thrombomodulin among knockout mice with sepsis relative to the wildtype.

Conclusions

We present genetic and biomarker association data that suggest a potential direct role of the PCSK9-LDLR pathway on Angpt-1 in the developing host with septic shock and warrant external validation. Further, mechanistic studies on the role of PCSK9-LDLR pathway on vascular homeostasis may lead to the development of pediatric-specific sepsis therapies.

Graphical abstract
Transcriptionally regulated miR-26a-5p may act as BRCAness in Triple-Negative Breast Cancer
Authors: Zhang Yue , Lv Lianqiu , Zheng Renjing , Xie Rong , Yu Yuanhang , Liao Han , Chen Jianying , Zhang Bo
Published: June 2023

Background

DNA damage and DNA damage repair (DDR) are important therapeutic targets for triple-negative breast cancer (TNBC), a subtype with limited chemotherapy efficiency and poor outcome. However, the role of microRNAs in the therapy is emerging. In this study, we explored whether miR-26a-5p could act as BRCAness and enhance chemotherapy sensitivity in TNBC.

Methods

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-26a-5p in breast cancer tissues and cell lines. CCK-8 was used to measure drug sensitivity in concentration gradient and time gradient. Comet assay was used to detect DNA damage. Flow cytometry was performed to examine apoptosis. Moreover, we used western blot and immunofluorescence to detect biomarkers. Luciferase reporter assay was performed to verify the combination of miR-26a-5p and 3’UTR of target gene. Hormone deprivation and stimulation assay were used to validate the effect of hormone receptors on the expression of miR-26a-5p. Chromatin immunoprecipitation (ChIP) assays were used to verify the binding sites of ER-a or PR with the promoter of miR-26a-5p. Animal experiments were performed to the effect of miR-26a-5p on Cisplatin treatment.

Results

The expression of miR-26a-5p was significantly downregulated in TNBC. Overexpressing miR-26a-5p enhanced the Cisplatin-induced DNA damage and following apoptosis. Interestingly, miR-26a-5p promoted the expression of Fas without Cisplatin stimulating. It suggested that miR-26a-5p provided a hypersensitivity state of death receptor apoptosis and promoted the Cisplatin sensitivity of TNBC cells in vitro and in vivo. Besides, miR-26a-5p negatively regulated the expression of BARD1 and NABP1 and resulted in homologous recombination repair defect (HRD). Notably, overexpressing miR-26a-5p not only facilitated the Olaparib sensitivity of TNBC cells but also the combination of Cisplatin and Olaparib. Furthermore, hormone receptors functioned as transcription factors in the expression of miR-26a-5p, which explained the reasons that miR-26a-5p expressed lowest in TNBC.

Conclusions

Taken together, we reveal the important role of miR-26a-5p in Cisplatin sensitivity and highlight its new mechanism in DNA damage and synthetic lethal.
Human papillomavirus integration transforms chromatin to drive oncogenesis
Authors: Karimzadeh Mehran , Arlidge Christopher , Rostami Ariana , Lupien Mathieu , Bratman Scott V. , Hoffman Michael M.
Published: June 2023

Background

Human papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs predominantly in tumorigenic types of HPV. We hypothesize that changes in chromatin state at the location of integration can result in changes in gene expression that contribute to the tumorigenicity of HPV.

Results

We find that viral integration events often occur along with changes in chromatin state and expression of genes near the integration site. We investigate whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF binding site, show enriched chromatin accessibility signal. ChIP-seq reveals that the conserved CTCF binding site within the HPV genome binds CTCF in 4 HPV﻿+cancer cell lines. Significant changes in CTCF binding pattern and increases in chromatin accessibility occur exclusively within 100 kbp of HPV integration sites. The chromatin changes co-occur with out-sized changes in transcription and alternative splicing of local genes. Analysis of The Cancer Genome Atlas (TCGA) HPV+tumors indicates that HPV integration upregulates genes which have significantly higher essentiality scores compared to randomly selected upregulated genes from the same tumors.

Conclusions

Our results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin state and upregulates genes essential for tumor viability in some HPV+tumors. These findings emphasize a newly recognized role of HPV integration in oncogenesis.
DCATS: differential composition analysis for flexible single-cell experimental designs
Authors: Lin Xinyi , Chau Chuen , Ma Kun , Huang Yuanhua , Ho Joshua W. K.
Published: June 2023

Differential composition analysis — the identification of cell types that have statistically significant changes in abundance between multiple experimental conditions — is one of the most common tasks in single cell omic data analysis. However, it remains challenging to perform differential composition analysis in the presence of flexible experimental designs and uncertainty in cell type assignment. Here, we introduce a statistical model and an open source R package, DCATS, for differential composition analysis based on a beta-binomial regression framework that addresses these challenges. Our empirical evaluation shows that DCATS consistently maintains high sensitivity and specificity compared to state-of-the-art methods.