bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the genes involved in the egg-carrying ovigerous hair development of the female blue crab Callinectes sapidus: transcriptomic and genomic expression analyses
Authors: Wang Tao , Bachvaroff Tsvetan , Chung J. Sook
Published: December 2023

Background

Crustacean female sex hormone (CFSH) controls gradually developing adult female-specific morphological features essential for mating and brood care. Specifically, ovigerous hairs are developed during the prepuberty molt cycle of the blue crab Callinectes sapidus that are essential for carrying the eggs until they finish development. Reduced CFSH transcripts by CFSH-dsRNA injections result in fewer and shorter ovigerous hairs than the control. This study aimed to identify the specific genes responsible for ovigerous hair formation using transcriptomic, genomic and expression analyses of the ovigerous setae at three stages: prepuberty at early (OE) and late premolt (OL), and adult (AO) stages.

Results

The de novo Trinity assembly on filtered sequence reads produced 96,684 Trinity genes and 124,128 transcripts with an N50 of 1,615 bp. About 27.3% of the assembled Trinity genes are annotated to the public protein sequence databases (i.e., NR, Swiss-Prot, COG, KEGG, and GO databases). The OE vs. OL, OL vs. AO, and OE vs. AO comparisons resulted in 6,547, 7,793, and 7,481 differentially expressed genes, respectively, at a log2-fold difference. Specifically, the genes involved in the Wnt signaling and cell cycle pathways are positively associated with ovigerous hair development. Moreover, the transcripts of ten cuticle protein genes containing chitin-binding domains are most significantly changed by transcriptomic analysis and RT-qPCR assays, which shows a molt-stage specific, down-up-down mode across the OE-OL-AO stages. Furthermore, the expression of the cuticle genes with the chitin-binding domain, Rebers and Riddiford domain (RR)-1 appears at early premolt, followed by RR-2 at late premolt stage. Mapping these 10 cuticle protein sequences to the C. sapidus genome reveals that two scaffolds with a 549.5Kb region and 35 with a 1.19 Mb region harbor 21 RR1 and 20 RR2 cuticle protein genes, respectively. With these findings, a putative mode of CFSH action in decapod crustaceans is proposed.

Conclusions

The present study describes a first step in understanding the mechanism underlying ovigerous hair formation in C. sapidus at the molecular level. Overall, demonstrating the first transcriptome analysis of crustacean ovigerous setae, our results may facilitate future studies into the decapod female reproduction belonging to the suborder Pleocyemata.
A park-based group mobility program for older adults with difficulty walking outdoors: a quantitative process evaluation of the Getting Older Adults Outdoors (GO-OUT) randomized controlled trial
Authors: Barclay Ruth , Webber Sandra C. , Hahn Francine , Jones C. Allyson , Mayo Nancy E. , Sivakumaran Shajicaa , Liu Yixiu , Chilibeck Philip D. , Salbach Nancy M.
Published: December 2023

Background

Process evaluations of randomized controlled trials (RCTs) of community exercise programs are important to help explain the results of a trial and provide evidence of the feasibility for community implementation. The objectives of this process evaluation for a multi-centre RCT of outdoor walking interventions for older adults with difficulty walking outdoors, were to determine: 1) implementation fidelity (the extent to which elements of the intervention were delivered as specified in the original protocol) and 2) participant engagement (the receipt of intervention components by the participants) in the Getting Older Adults Outdoors (GO-OUT) trial.

Methods

GO-OUT participants attended an active 1-day workshop designed to foster safe, outdoor walking skills. After the workshop, 190 people at 4 sites were randomized to an outdoor walk group (OWG) (n = 98) which met 2x/week for 10 weeks, or the weekly reminders (WR) group (n = 92) which received a phone reminder 1x/week for 10 weeks. The OWG had 5 components – warm-up, continuous distance walk, task-oriented walking activities, 2nd continuous distance walk, and cool-down. Data on implementation fidelity and participant engagement were gathered during the study through site communications, use of standardized forms, reflective notes of the OWG leaders, and accelerometry and GPS assessment of participants during 2 weeks of the OWG.

Results

All sites implemented the workshop according to the protocol. Participants were engaged in all 8 activity stations of the workshop. WR were provided to 96% of the participants in the WR intervention group. The 5 components of the OWG sessions were implemented in over 95% of the sessions, as outlined in the protocol. Average attendance in the OWG was not high – 15% of participants did not attend any sessions and 64% of participants in the OWG attended > 50% of the sessions. Evaluations with accelerometry and GPS during week 3 and 9 OWG sessions suggest that participants who attended were engaged and active during the OWG.

Conclusions

This process evaluation helps explain the main study findings and demonstrates the flexibility required in the protocol for safe and feasible community implementation. Future research could explore the use of additional behaviour change strategies to optimize attendance for community implementation.

Trial registration

ClinicalTrials.gov NCT03292510 Date of registration: September 25, 2017.
Challenging experiences of the elderly with heart failure in the COVID-19 pandemic: a phenomenological study in Iran
Authors: Ziapour Arash , Lebni Javad Yoosefi , Mohammadkhah Fatemeh , Chaboksavar Fakhreddin , Janjani Parisa , Yıldırım Murat
Published: December 2023

Background

Patients with heart failure (HF), especially the elderly, faced many challenges during the COVID-19 pandemic, which need to be explored. The present study aimed to analyse the challenging experiences facing the elderly with heart failure during the pandemic in Iran. To achieve this aim, a qualitative approach to research was employed.

Methods

The present qualitative research employed a phenomenological approach to study 12 elderly with heart failure visiting Imam Ali Hospital during the COVID-19 pandemic in Kermanshah, Iran. The data collection occurred between August 5, 2022, and November 21, 2022. The participants were selected through a purposive sampling method and interviewed using a semi-structured interview. MAXQDA10 software was used for data organisation and the Colizzi analytical technique for data analysis. Guba and Lincoln’s criteria were also used to evaluate the trustworthiness of the qualitative research.

Results

A total of two categories, 8 subcategories, and 110 primary codes were extracted from the data. The two categories were challenges and coping strategies. The former included the sub-categories of economic issues, fear, anxiety, and fear of death; limited access to health care; quarantine issues; disruption of family life; and medication non-adherence. The subcategories of the latter were faith in God, social support, and self-care behaviors.

Conclusions

The present study revealed the challenges experienced and the coping strategies employed by elderly patients with heart failure during the pandemic in Iran. A knowledge of these challenges and experiences during the COVID-19 pandemic can raise healthcare workers’ awareness of the elderly patients’ strategies used to cope with the virus.
Vitamin C reduces the severity of common colds: a meta-analysis
Authors: Hemilä Harri , Chalker Elizabeth
Published: December 2023

Background

Randomized trials have shown that vitamin C shortens the duration of common colds. Some trials reported greater effects on severe cold symptoms compared with mild symptoms. This review systematically compares the effects of vitamin C on severe and mild common cold symptoms.

Methods

We included all placebo-controlled trials of orally administered vitamin C in doses of at least 1 g/day for the common cold for people in good health at baseline. The analysis was restricted to trials which reported both the total duration of the common cold, and the severity of the common cold measured using severity scales, the duration of more severe stages of the cold, or proxies for severe colds such as days indoors. Findings were pooled using the inverse variance, fixed effect options of the metacont function of the R package meta to calculate the ratio of means estimate.

Results

Fifteen comparisons from 10 trials which reported both mild and severe symptoms were identified. All trials were randomized and double-blind. Compared to placebo, vitamin C significantly decreased the severity of the common cold by 15% (95% CI 9–21%). The direct comparison of the effect of vitamin C on mild and severe symptoms was limited to five comparisons which found that vitamin C had a significant benefit on the duration of severe symptoms. In this subset, there was a significant difference in the size of the effect of vitamin C on the overall duration of colds versus the duration of severe colds (P = 0.002), and vitamin C had no significant effect on the duration of mild symptoms.

Conclusions

The common cold is the leading cause of acute morbidity and a major cause of absenteeism from work and school. However, absenteeism is dependent on the severity of symptoms. The finding that vitamin C may have a greater effect on more severe measures of the common cold is therefore important. Further research on the therapeutic effects of vitamin C on the common cold should measure outcomes of differing levels of severity.
Contents of antenatal care services in Afghanistan: findings from the national health survey 2018
Authors: Stanikzai Muhammad Haroon , Tawfiq Essa , Jafari Massoma , Wasiq Abdul Wahed , Seddiq Mohammad Khaled , Currie Sheena , Sayam Hadia , Baray Ahmad Haroon , Saeedzai Sayed Ataullah
Published: December 2023

Background

Maternal and newborn mortality is a public health concern in low- and middle-income countries (LMICs), including Afghanistan, where the evolving socio-political circumstances have added new complexities to healthcare service delivery. Birth outcomes for both pregnant women and their newborns are improved if women receive benefits of quality antenatal care (ANC).

Objectives

This study aimed to assess the contents of ANC services and identify predictors of utilization of services by pregnant women during ANC visits to health facilities in Afghanistan.

Methods

In this cross-sectional study, we used data from the Afghanistan Health Survey 2018 (AHS2018). We included a total of 6,627 ever-married women, aged 14–49 years, who had given birth in the past 2 years or were pregnant at the time of survey and had consulted a health worker for ANC services in a health facility. The outcome was defined as 1–4 services and 5–8 services that a pregnant woman received during an ANC visit. The services were (i) taking a pregnant woman’s blood pressure, (ii) weighing her, (iii) testing her blood, (iv) testing her urine, (v) providing advice on nutrition, (vi) advising about complicated pregnancy, (vii) advising about the availability of health services, and (viii) giving her at least one dose of Tetanus Toxoid (TT) vaccine. The binary outcome (1–4 services versus 5–8 services) was used in a multivariable logistic regression model.

Results

Of all 6,627 women, 31.4% (2,083) received 5–8 services during ANC visits. Only 1.3% (86) received all 8 services, with 98.7% (6,541) receiving between 1 and 7 services, and 71.6% (4,745) women had their blood pressure measured during ANC visits. The likelihood (adOR = Adjusted Odds Ratio) of receiving 5–8 services was higher in women who could read and write (adOR = 1.33: 1.15–1.54), in women whose husbands could read and write (adOR = 1.14: 1.00-1.28), in primipara women (adOR = 1.42: 1.02–1.98), in women who knew one danger sign (adOR = 5.38: 4.50–6.45), those who knew 2 danger signs (adOR = 8.51: 7.12–10.19) and those who knew ≥ 3 danger signs (adOR = 13.19: 10.67–16.29) of complicated pregnancy, and in women who had almost daily access to TV (adOR = 1.16: 1.01–1.33). However, the likelihood of receiving 5–8 services was lower in women who used private clinics (adOR = 0.64: 0.55–0.74) and who received services from nurses (adOR = 0.27 (0.08–0.88).

Conclusion

Our findings have the potential to influence the design and implementation of ANC services of health interventions to improve the delivery of services to pregnant women during ANC visits.
Predicting efficacy and guiding procedure choice in non-vascularized bone grafting: a CT Radiomics and clinical predictor approach
Authors: Chen Hao , Xue Peng , Xi Hongzhong , He Shuai , Sun Guangquan , Liu Xin , Du Bin
Published: December 2023

Objectives

There is no practical approach for accurately predicting the efficacy of non-vascularized bone grafting (NVBG) and guiding its optimal procedure.

Materials and methods

This study enrolled 153 patients with 182 hips that underwent NVBG procedures. The patients were randomly divided into a training cohort (n = 130) and a validation cohort (n = 52). In the training cohort, radiomics model, clinical model, and combined radiomics-clinical (C-R) model were constructed using Rad-scores and clinical predictors to predict the efficacy of NVBG. The optimal model was visualized by a nomogram and assessed by decision curve analysis (DCA). 128 hips that underwent successful NVBG were then randomized into a new training cohort (n = 92) and a new validation cohort (n = 36), and three models were constructed and validated to predict the choice of NVBG procedure.

Results

Japanese Investigation Committee (JIC) classification, exposure to risk factors postoperative, and Rad-scores consisting of four radiomics features were independent predictors for the efficacy of NVBG (P < 0.05). The C-R model provided better performance in both the training cohort (AUC: 0.818) and validation cohort (AUC: 0.747). To predict the choice of NVBG procedure, the C-R model built by JIC classification and Rad-scores consisting of five radiomics features showed the finest performance in both cohorts (AUC: 0.860 and 0.800, respectively). DCA showed great benefit using the C-R model for the choice of NVBG procedure.

Conclusion

The approach integrated by CT radiomics and clinical predictors can be visually and quantitatively applied to predict the efficacy and guide the choice of NVBG procedure with great predictive accuracy.
Effect of lactoferrin on enamel characteristics of primary and permanent teeth: an in-vitro study
Authors: Atia Nouran Samir Mohamed , El-nemr Reham Ahmed , Abo-Elsoud Asmaa Ali Emam
Published: December 2023

Background

Lactoferrin, a glycoprotein naturally found in breast milk, is known for its bactericidal and antiviral properties, as well as its capacity to modulate the immune system; therefore, pediatricians routinely recommend it as dietary support. The objective of this study was to determine how lactoferrin oral suspension could affect the enamel surface characteristics of primary and permanent teeth.

Methods

This research was conducted on 40 unidentified extracted teeth, including primary and permanent teeth. Experimental teeth were free of cracks or enamel defects, as confirmed by careful examination using a dental operating microscope. The crowns were bisected into 80 specimens and assorted into two groups based on the type of dentition. Group DM included 40 specimens of second deciduous molars, while Group PM contained 40 samples of first premolars. Each of the DM and PM specimens was subsequently split based on the type of dispersion medium into two subgroups: a control subgroup (artificial saliva) and a test subgroup (lactoferrin suspension). The specimens were immersed in lactoferrin suspension for two minutes, then kept in artificial saliva for the rest of the 24 h for 30 successive days. This is a pioneering study about the effect of orally supplemented lactoferrin on teeth; therefore, we examined enamel hardness, ultra-morphology, and mineral contents.

Results

Our findings indicated a highly significant decrease (p < 0.01) in the microhardness of the lactoferrin subgroup in Group DM (second deciduous molars) and a significant reduction (p < 0.05) in the microhardness of the lactoferrin subgroup in Group PM (premolars). Calcium weight% was not statistically different (p > 0.05) compared with a significant decline (p < 0.05) in phosphorus weight% in lactoferrin subgroups in both DM and PM groups. The enamel surface of lactoferrin subgroups in both DM and PM groups was demineralized and porous, with the enamel of deciduous teeth being more affected by lactoferrin than permanent teeth.

Conclusion

Lactoferrin suspension decreased the microhardness of enamel and both calcium and phosphorus weight percentages. Both dentitions exhibited erosions in the enamel surface, with primary teeth being more affected than the permanent teeth.
Reliability, validity and distribution of the Spanish female sexual function index in women with relapsing multiple sclerosis
Authors: Gil-Perotin Sara , Reddam Salma , González-Mingot Cristina , Gil-Sánchez Anna , González-Suarez Inés , Peralta Silvia , Escrivá Patricia , Barea-Moya Lucas , Sánchez-Sánchez Beatriz
Published: December 2023

Background

The Female Sexual Function Index (FSFI) is a widely recognized tool for assessing sexual dysfunction (SD). However, its validation for Spanish women suffering from multiple sclerosis (MS) has not yet been conducted.

Aim

The study aimed to examine the psychometric properties of the 19-item Spanish version of the FSFI (svFSFI) in women with relapsing MS.

Method

A total of 137 women with relapsing MS from three Spanish centers participated in the study and completed the svFSFI. The psychometric properties of the questionnaire were evaluated. The prevalence of SD in the study cohort was determined, and its association with clinical and sociodemographic variables was analyzed using bi- and multivariate regression analyses.

Results

The svFSFI demonstrated excellent test-retest reliability and substantial-to-excellent internal consistency in the context of relapsing MS. There was significant convergent validity in the intercorrelations of domains. Discriminant validity showed differences in SD between women with high and low neurological disability, as measured by the Expanded Disability Status Scale (EDSS) scores. An exploratory factor analysis indicated a five-factor structure for the svFSFI. The prevalence of SD in the MS cohort was found to be 42.6%, with the ‘desire’ and ‘arousal’ domains being the most affected. Factors such as EDSS score, fatigue, depression, and having a stable partner were found to influence the total svFSFI score.

Conclusion

The study validates the svFSFI as a reliable and valid instrument for evaluating sexual dysfunction in Spanish women with MS.
“Gender-based Violence (GBV) and HIV, they are like sister and brother”: barriers and facilitators to GBV screening and referral in public HIV treatment settings in Uganda
Authors: Thomas Dorothy , Nalumansi Alisaati , Reichman Mira , Metitiri Mine , Kamusiime Brenda , Kasiita Vicent , Nalukwago Grace K , Kibuuka Joseph , Nakabugo Lylianne , Nambi Florence , Muwonge Timothy , Simoni Jane , Montgomery Elizabeth T. , Ware Norma , Wyatt Monique A , Mujugira Andrew , Heffron Renee
Published: December 2023

Background

People living with HIV are vulnerable to gender-based violence (GBV), which can negatively impact HIV treatment outcomes. National guidelines in Uganda recommend GBV screening alongside HIV treatment services. We explored barriers and facilitators to providers implementing GBV screening and referral in public antiretroviral therapy (ART) clinics in Uganda.

Methods

We conducted qualitative in-depth interviews. Providers were purposively sampled from 12 ART clinics to represent variation in clinical specialty and gender. We used the Theoretical Domains Framework to structure our deductive analysis.

Results

We conducted 30 in-depth interviews with providers implementing GBV screening and/or referral. Respondents had a median age of 36 (IQR: 30, 43) years and had been offering post-GBV care to clients for a median duration of 5 (4, 7) years. 67% of respondents identified as female and 57% were counselors. Facilitators of GBV screening and referral included providers having access to post-GBV standard operating procedures and screening tools, trainings offered by the Ministry of Health, facility-sponsored continuing medical education units and support from colleagues. Respondents indicated that referrals were uncommon, citing the following barriers: negative expectations regarding the quality and quantity of referral services; lack of financial resources to support clients, facilities, and referral partners throughout the referral process; and sociocultural factors that threatened client willingness to pursue post-GBV support services.

Conclusions

Findings from this evaluation support the refinement of GBV screening and referral implementation strategies that leverage facilitators and address barriers to better support individuals living with HIV and who may have heightened vulnerability to GBV.
Y chromosome AZFc microdeletion may have negative effect on embryo euploidy: a retrospective cohort study
Authors: Jiang Wei , Xie Qijun , Li Xin , Yang Ye , Luan Ting , Ni Danyu , Chen Yuting , Wang Xinyu , Zhao Chun , Ling Xiufeng
Published: December 2023

Background

Embryo aneuploidy is a main of principal reason of pregnancy loss, in vitro fertilization (IVF) failure and birth defects in offspring. Previous researchs have demonstrated that Y chromosome AZFc microdeletion was associated with reproduction outcomes, however, the relationship between Y chromosome AZFc microdeletion and embryo aneuploidy remains unexplored.

Methods

This retrospective cohort study enrolled 513 patients with 603 cycles in the reproductive center of Nanjing Maternity and Child Health Care Hospital from January 1, 2016 to June 30, 2022. The study cohort was divided into two groups: the AZFc microdeletion group, comprising 53 patients and 58 cycles, and the control group, comprising 460 patients and 545 cycles. Statistical methods including restricted cubic spline and generalized estimating equation (GEE) were employed to evaluate the relationship between Y chromosome AZFc microdeletion and embryo euploidy.

Results

294 and 2833 blastocysts were selected as AZFc microdeletion group and control group, respectively. Patients with Y chromosome AZFc microdeletion had significantly higher embryo aneuploid rate (33.0% vs. 27.3%, P < 0.05), lower rate of normal fertilization rate (81.5% vs. 90.3%, P < 0.05) and lower blastocysts formation rate (47.0% vs. 57.8%, P < 0.05) compared with the control group. However, no significant differences in pregnancy outcomes after euploid embryos transfer were observed between these two groups.

Conclusions

Our study underscored the association between Y chromosome AZFc microdeletion and an elevated risk of embryo aneuploidy. Before the conventional intracytoplasmic sperm injection (ICSI) treatment, couples with Y chromosome AZFc microdeletion should be apprised of the heightened susceptibility to embryo aneuploidy. Preimplantation genetic testing for aneuploidy (PGT-A) should be introduced for selection.
How the National Health Insurance Coverage policy changed the use of lenvatinib for adult patients with advanced hepatocellular carcinoma: a retrospective cohort analysis with real world big data
Authors: Liu Yanyan , Bao Yuwen , Huang Yaxin , Zhang Mengdie , Li Xin
Published: December 2023

Background

To establish a long-term mechanism to control the cost burden of drugs, the Chinese government organized seven rounds of price negotiations for the national reimbursement drug list (NRDL) from 2016 to the end of 2022. The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the use of lenvatinib as the first-line treatment for advanced hepatocellular carcinoma (HCC) within a specific medical insurance region from the micro perspective of individual patient characteristics.

Methods

The data of HCC patients that received lenvatinib from September 2019 to August 2022 was retrieved from the Medical and Health Big Data Center and longitudinally analyzed. Contingency table chi-square statistics and binary logistic regression analysis were used to compare the differences in the categorical variables. Interrupted time-series (ITS) regression analysis was performed to evaluate the changes in the utilization of lenvatinib over 36 months. Multiple linear regression was used to analyze the impact of receiving lenvatinib on the total hospitalization expenses of hospitalized patients with advanced HCC.

Results

A total of 12,659 patients with advanced HCC were included in this study. The usage rate of lenvatinib increased from 6.19% to 15.28% over 36 months (P < 0.001). By controlling the other factors, consistent with this, the probability of patients with advanced HCC receiving lenvatinib increased by 2.72-fold after the implementation of the NHIC policy (OR = 2.720, 95% CI:2.396–3.088, P < 0.001). Older, residency in rural areas, lack of fixed income, treatment at hospitals below the tertiary level, and coverage by urban-rural residents’ basic medical insurance (URRBMI) were the factors affecting the use of lenvatinib among patients with advanced HCC (P < 0.05). After the implementation of the NHIC policy, the total hospitalization expenses increased (Beta=-0.040, P < 0.001). However, compared to patients who received lenvatinib, the total hospitalization expenses were higher for those who did not receive the drug (US$5022.07 ± US$5488.70 vs. US$3701.63 ± US$4330.70, Beta = 0.062, P < 0.001).

Conclusions

The NHIC policy has significantly increased the utilization of lenvatinib. In addition, we speculate that establishing multi-level medical insurance systems for economically disadvantaged patients would be beneficial in improving the effectiveness of the NHIC policy in the real world.
Transcranial direct current stimulation for post-stroke dysphagia: a meta-analysis
Authors: Gómez-García Nerea , Álvarez-Barrio Lorena , Leirós-Rodríguez Raquel , Soto-Rodríguez Anxela , Andrade-Gómez Elena , Hernández-Lucas Pablo
Published: December 2023

Background

Strokes may cause some swallowing difficulty or associated dysphagia in 25–80% of patients. This phenomenon has been linked to increased morbidity and mortality. Therefore, the aim of this study was to evaluate the efficacy of transcranial direct current stimulation in patients with dysphagia in post-stroke patients.

Methods

A systematic search in PubMed, Scopus, Web of Science and MEDLINE was conducted. The articles must have to evaluate an intervention that included transcranial direct current stimulation; the sample had to consist exclusively of patients with post-stroke dysphagia; and the experimental design consisted of randomized controlled trial. Difference in mean differences and their 95% confidence interval were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity.

Results

Of the 9 investigations analyzed, all applied transcranial direct current stimulation in combination with conventional dysphagia therapy to the experimental group. All the studies analyzed identified improvements in swallowing function and meta-analysis confirmed their strong effect on reducing the risk of penetration and aspiration (Hedges’s g = 0.55). The results showed that participants who received transcranial direct current stimulation significantly improved swallowing function.

Conclusions

Transcranial direct current stimulation has positive effects in the treatment of poststroke dysphagia by improving swallowing function, oral and pharyngeal phase times and the risk of penetration and aspiration. Furthermore, its combination with conventional dysphagia therapy, balloon dilatation with catheter or training of the swallowing muscles ensures improvement of swallowing function.

PROSPERO registration ID CRD42022314949
Comparison of percutaneous endoscopic interlaminar discectomy and conventional open lumbar discectomy for L4/5 and L5/S1 double-segmental lumbar disk herniation
Authors: Tang Yingchuang , Li Hanwen , Qin Wanjin , Liu Zixiang , Liu Hao , Zhang Junxin , Mao Haiqing , Zhang Kai , Chen Kangwu
Published: December 2023

Objective

Although spinal endoscopic techniques have shown great advantages in the treatment of single-segment lumbar disk herniation (LDH), the therapeutic advantages for double-segment LDH are controversial. To compare the outcomes of percutaneous endoscopic interlaminar discectomy (PEID) versus conventional open lumbar discectomy (COLD) for the treatment of L4/5 and L5/S1 double-segmental LDH.

Methods

From January 2016 to September 2021, we included 50 patients with double-segmental LDH who underwent PEID (n = 25) or COLD (n = 25). The clinical outcomes between the two groups were evaluated using the visual analog scale (VAS), the Oswestry disability index (ODI), and the modified MacNab criteria. Moreover, the incision length, operation time, intraoperative fluoroscopy time, postoperative bedtime, hospital stays, and complications were also recorded and compared after surgery.

Results

In both groups, the VAS and ODI scores at different timepoints postoperatively were significantly improved compared with those preoperatively (P < 0.05) According to the modified MacNab criteria, the excellent or good outcome rate was 92% in the PEID group and 88% in the COLD group. The PEID group had shorter incision length, postoperative bedtime, and hospital stays than the COLD group. However, the operation time was shorter and intraoperative fluoroscopy time was fewer in the COLD group. In addition, there was no significant difference between the two groups in terms of surgical complications during the postoperative follow-up period.

Conclusions

Both PEID and COLD have good efficacy and high safety for management of L4/5 and L5/S1 double-segmental LDH. Compared with the COLD group, the PEID group had more operative time as well as more intraoperative fluoroscopy, but it had a more minimally invasive surgical incision as well as faster postoperative recovery.
Associations between spinal flexibility and bracing outcomes in adolescent idiopathic scoliosis: a literature review
Authors: Luo Chang Liang , Ma Christina Zong Hao , Zou Yi Ying , Zhang Li Sha , Wong Man Sang
Published: December 2023

Objectives

To identify the existing assessment methods used to measure the spinal flexibility of adolescents with idiopathic scoliosis before bracing and to evaluate the predictive effect of spinal flexibility on bracing outcomes.

Methods

A broad literature search was performed in the PubMed, Web of Science, EMBASE, CINAHL, Scopus, and Cochrane Library databases to obtain relevant information about spinal flexibility and bracing outcomes. All literature was retrieved by October 14, 2023. The inclusion and exclusion criteria were meticulously determined. The quality of each included study and the level of evidence were evaluated by the Quality in Prognosis Studies (QUIPS) method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system, respectively.

Results

After screening 1863 articles retrieved from databases, a total of 14 studies with 2261 subjects were eligible for the final analysis in this review. Overall, nine methods of flexibility assessment were identified, including supine radiographs, supine lateral bending radiographs, lateral bending radiographs but without clear positions, hanging radiographs, fulcrum bending physical method, and ultrasound imaging in the positions of supine, prone, sitting with side bending and prone with side bending. In addition, five studies demonstrated that flexibility had a strong correlation with in-brace correction, and eleven studies illustrated that spinal flexibility was a predictive factor of the bracing outcomes of initial in-brace Cobb angle, initial in-brace correction rate, curve progression, and curve regression. The results of GRADE demonstrated a moderate-evidence rating for the predictive value of spinal flexibility.

Conclusion

Supine radiography was the most prevalent method for measuring spinal flexibility at the pre-brace stage. Spinal flexibility was strongly correlated with the in-brace Cobb angle or correction rate, and moderate evidence supported that spinal flexibility could predict bracing outcomes.
A multicomponent intervention program to Prevent and Reduce AgItation and phySical rEstraint use in the ICU (PRAISE): study protocol for a multicenter, stepped-wedge, cluster randomized controlled trial
Authors: Kooken Rens W. J. , Tilburgs Bram , ter Heine Rob , Ramakers Bart , van den Boogaard Mark ,   on behalf of the PRAISE study group, Wiggelo-Lijbers Dieke , Klop-Riehl Margreet , Rettig Thijs C.D. , Wijnhoven JanWillem , Simons Bram , van de Weyer Rens , Bakker Stephanie , de Ruijter Wouter , Slot Stefanie , Braker-Scholtes Stefanie , Bruin Liz , Habes Quirine , Meeuws Sanne , Fleuren-Janssen Manon
Published: December 2023

Background

Physical restraints remain to be commonly used in agitated intensive care unit (ICU) patients worldwide, despite a lack of evidence on efficacy and safety and reports of detrimental short and long-term consequences, such as prolonged delirium and a longer ICU length of stay. Physical restraint minimization approaches have focused mainly on educational strategies and other non-pharmacological interventions. Combining these interventions with goal-directed light sedation therapy if needed may play an important contributory role in further reducing the use of physical restraints. The aim of the study is to determine the effectiveness of a multicomponent intervention (MCI) program, combining person-centered non-pharmacological interventions with goal-directed light sedation, compared to physical restraints.

Methods

A multicenter stepped-wedge cluster randomized controlled trial will be conducted in six Dutch ICUs. A power calculation based total of 480 (expected to become) agitated adult patients will be included in 26 months with a subsequent 2-year follow-up. Patients included in the control period will receive standard care with the current agitation management protocol including physical restraints. Patients included in the intervention period will be treated with the MCI program, consisting of four components, without physical restraints: education of ICU professionals, identification of patients at risk for agitation, formulation of a multidisciplinary person-centered care plan including non-pharmacological and medical interventions, and protocolized goal-directed light sedation using dexmedetomidine. Primary outcome is the number of days alive and outside of the ICU within 28 days after ICU admission. Secondary outcomes include length of hospital stay; 3-, 12-, and 24-month post-ICU quality of life; physical (fatigue, frailty, new physical problems), mental (anxiety, depression, and post-traumatic stress disorder), and cognitive health; and 1-year cost-effectiveness. A process evaluation will be conducted.

Discussion

This will be the first multicenter randomized controlled trial determining the effect of a combination of non-pharmacological interventions and light sedation using dexmedetomidine compared to physical restraints in agitated ICU patients. The results of this study, including long-term patient-centered outcomes, will provide relevant insights to aid ICU professionals in the management of agitated patients.

Trial registration

NCT05783505, registration date 23 March 2023.
Statistical optimization and gamma irradiation on cephalosporin C production by Acremonium chrysogenum W42-I
Authors: Ibrahim Asmaa A. , El-Housseiny Ghadir S. , Aboshanab Khaled M. , Startmann Ansgar , Yassien Mahmoud A. , Hassouna Nadia A.
Published: December 2023

Most antibiotics now used in clinical practice are cephalosporins. Acremonium (A.) chrysogenum W42-I is an intermediate strain out of W42 strain improvement program whose productivity is above that of the wild-type strain to produce the broad-spectrum antibacterial cephalosporin C (CPC). As a result, fermentation process optimization is considered because it offers the ideal environment for strains to reach their full potential. Our research aimed to combine a rational design to regulate the fermentation process environment and culture media as well as to develop mutants with high productivity. Different media were tested to obtain maximum CPC production. To maximize the production of CPC, some environmental parameters were experimentally optimized via the Box-Behnken design used for response surface methodology (RSM). There were 17 tests conducted, and each experiment's reaction was recorded. Improvement of the CPC production was further achieved via mutagenesis using gamma radiation. Results revealed that a pH of 4, an incubation period of 4 days, and an inoculum size of 1% v/v using the optimized media (CPC2) were the optimum conditions for enhancing the CPC production by 4.43-fold. In addition, gamma irradiation further enhanced production to reach 3.46-fold using an optimum dose of 2 KGy. In conclusion, in comparison to initial production levels, CPC production increased 4.43-fold because of nutritional and environmental optimization. The mutant AC8 demonstrated a roughly 3.46-fold increase in activity against its parent type. Moreover, subsequent AC8 mutant culture demonstrated excellent genetic stability.
New clinical application prospects of artemisinin and its derivatives: a scoping review
Authors: Huang Yangmu , Yang Yang , Liu Guangqi , Xu Ming
Published: December 2023

Background

Recent research has suggested that artemisinin and its derivatives may have therapeutic effects on parasites, viruses, tumors, inflammation and skin diseases. This study aimed to review clinical research on artemisinin and its derivatives except anti-malaria and explore possible priority areas for future development.

Methods

Relevant articles in English and Chinese published before 28 October 2021 were reviewed. All articles were retrieved and obtained from databases including WanFang, PubMed/MEDLINE, the Cochrane Library, China National Knowledge International, Embase, OpenGrey, the Grey Literature Report, Grey Horizon, and ClinicalTrials.gov. Studies were selected for final inclusion based on predefined criteria. Information was then extracted and analyzed by region, disease, outcome, and time to identify relevant knowledge gaps.

Results

Seventy-seven studies on anti-parasitic (35), anti-tumor (16), anti-inflammatory (12), anti-viral (8), and dermatological treatments (7) focused on the safety and efficacy of artemisinin and its derivatives. The anti-parasitic clinical research developed rapidly, with a large number of trials, rapid clinical progress, and multiple research topics. In contrast, anti-viral research was limited and mainly stayed in phase I clinical trials (37.50%). Most of the studies were conducted in Asia (60%), followed by Africa (27%), Europe (8%), and the Americas (5%). Anti-parasite and anti-inflammatory research were mainly distributed in less developed continents such as Asia and Africa, while cutting-edge research such as anti-tumor has attracted more attention in Europe and the United States. At the safety level, 58 articles mentioned the adverse reactions of artemisinin and its derivatives, with only one study showing a Grade 3 adverse event, while the other studies did not show any related adverse reactions or required discontinuation. Most studies have discovered therapeutic effects of artemisinin or its derivatives on anti-parasitic (27), anti-tumor (9), anti-inflammatory (9) and dermatological treatment (6). However, the efficacy of artemisinin-based combination therapies (ACTs) for parasitic diseases (non-malaria) is still controversial.

Conclusions

Recent clinical studies suggest that artemisinin and its derivatives may be safe and effective candidates for anti-tumor, anti-parasitic, anti-inflammatory and dermatological drugs. More phase II/III clinical trials of artemisinin and its derivatives on antiviral effects are needed.

Graphical Abstract
An evolved pyrrolysyl-tRNA synthetase with polysubstrate specificity expands the toolbox for engineering enzymes with incorporation of noncanonical amino acids
Authors: Liu Ke , Jiang Ling , Ma Shuang , Song Zhongdi , Wang Lun , Zhang Qunfeng , Xu Renhao , Yang Lirong , Wu Jianping , Yu Haoran
Published: December 2023

Aminoacyl-tRNA synthetase (aaRS) is a core component for genetic code expansion (GCE), a powerful technique that enables the incorporation of noncanonical amino acids (ncAAs) into a protein. The aaRS with polyspecificity can be exploited in incorporating additional ncAAs into a protein without the evolution of new, orthogonal aaRS/tRNA pair, which hence provides a useful tool for probing the enzyme mechanism or expanding protein function. A variant (N346A/C348A) of pyrrolysyl-tRNA synthetase from Methanosarcina mazei (MmPylRS) exhibited a wide substrate scope of accepting over 40 phenylalanine derivatives. However, for most of the substrates, the incorporation efficiency was low. Here, a MbPylRS (N311A/C313A) variant was constructed that showed higher ncAA incorporation efficiency than its homologous MmPylRS (N346A/C348A). Next, N-terminal of MbPylRS (N311A/C313A) was engineered by a greedy combination of single variants identified previously, resulting in an IPE (N311A/C313A/V31I/T56P/A100E) variant with significantly improved activity against various ncAAs. Activity of IPE was then tested toward 43 novel ncAAs, and 16 of them were identified to be accepted by the variant. The variant hence could incorporate nearly 60 ncAAs in total into proteins. With the utility of this variant, eight various ncAAs were then incorporated into a lanthanide-dependent alcohol dehydrogenase PedH. Incorporation of phenyllactic acid improved the catalytic efficiency of PedH toward methanol by 1.8-fold, indicating the role of modifying protein main chain in enzyme engineering. Incorporation of O-tert-Butyl-L-tyrosine modified the enantioselectivity of PedH by influencing the interactions between substrate and protein. Enzymatic characterization and molecular dynamics simulations revealed the mechanism of ncAAs affecting PedH catalysis. This study provides a PylRS variant with high activity and substrate promiscuity, which increases the utility of GCE in enzyme mechanism illustration and engineering.

Graphical Abstract
Spatial and temporal disparities in air pollution exposure at Italian schools
Authors: Conte Keivabu Risto
Published: December 2023

Air pollution poses major threats to children’s health and learning, making exposure at school particularly critical. However, some children are more exposed than others, especially depending on the socioeconomic status of their school’s neighbourhood. In this study, we explore how exposure to air pollution varies across schools, over time and by the socioeconomic characteristics of the neighbourhood using data on approximately 23 thousand schools in Italy connected with estimates on Particulate Matter 2.5 measured in µg/m3 at a 1 × 1 km resolution from 2002 to 2018 provided by the Atmospheric Composition Analysis Group (ACAG). Moreover, we create an indicator of school socioeconomic status (SES) using fine-grained information on the real estate value made available by the Italian Observatory of Real Estate Value. Results highlight three main findings. First, air quality at the location of the schools improved over time by about 35%. Secondly, SES shows an inverted U-curve with PM2.5 suggesting schools in middle SES neighbourhoods to be exposed to the highest levels of pollution. Thirdly, SES does not show a substantive association with a decrease in air pollution over time. In conclusion, air quality has improved over time in Italy, but schools still do not comply with the World Health Organization (WHO) standards and middle SES neighbourhoods remain the most exposed to air pollution.
Bortezomib in the management of anti-NMDA receptor encephalitis
Authors: de Liyis Bryan Gervais , Sutedja Jane Carissa , Evananda Maria Pramesthi Sabrina , Wibisono Ledwin Meikel , Karuniamaya Chrysanta Paramitha , Soetomo Cindy Thiovany , Susilawathi Ni Made
Published: December 2023

Background

Anti-N-methyl d-aspartate (NMDA) receptor encephalitis is an autoimmune encephalitis characterized by neuronal surface antibodies targeting NMDA receptor in the spinal fluid and serum. After acute disseminated encephalomyelitis, anti-NMDA receptor encephalitis is the most frequent cause of autoimmune encephalitis. Despite its clinical significance, the exact prevalence and optimal treatment strategies for this condition remain poorly understood. This comprehensive review aims to evaluate the therapeutic potential of bortezomib as a novel therapy for anti-NMDA receptor encephalitis in hopes of mitigating symptoms and improving outcomes for anti-NMDA receptor encephalitis patients.

Results

The disease is primarily triggered by immunoreactivity against the NMDA receptor 1 (NR1). Recurrence rates are of significant concern in the treatment of anti-NMDA receptor encephalitis, given that a substantial portion of patients are unresponsive to immunosuppressive and immunomodulatory therapies. Thus, the exploration of alternative therapies is necessary. In recent years, bortezomib, a proteasome inhibitor, has emerged as a potential therapeutic candidate by inhibiting autoantibody production against NMDA receptor. Bortezomib exerts immunosuppressive and immunomodulatory effects by inhibiting the production of autoantibodies against NMDA receptor. Studies suggest that bortezomib, by inhibiting proteasome activity and altering antigen presentation, can suppress autoantibody production and immune cell activation, contributing to clinical improvement. However, literature reviews on the utilization of bortezomib in the context of anti-NMDA receptor encephalitis are still highly limited.

Conclusions

Bortezomib presents a promising avenue for intervention. While initial studies suggest its potential to modify the immune response and alleviate symptoms, further comprehensive investigations are imperative to establish optimal dosing, usage guidelines, and long-term safety profiles.