bluuebunny/crossref_metadata_2025 huggingface dataset:
RTS,S/AS01 malaria vaccine pilot implementation in western Kenya: a qualitative longitudinal study to understand immunisation barriers and optimise uptake
Authors: Hoyt Jenna , Okello George , Bange Teresa , Kariuki Simon , Jalloh Mohamed F. , Webster Jayne , Hill Jenny
Published: November 2023

Background

Malaria is a significant public health threat in sub-Saharan Africa, particularly among children. The RTS,S/AS01 malaria vaccine reduces the risk and severity of malaria in children. RTS,S/AS01 was piloted in three African countries, Ghana, Kenya and Malawi, to assess safety, feasibility and cost-effectiveness in real-world settings. A qualitative longitudinal study was conducted as part of the feasibility assessment. This analysis explores RTS,S/AS01 vaccination barriers and identifies potential motivators among caregivers in three sub-counties in western Kenya.

Methods

A cohort of 63 caregivers with a malaria vaccine eligible child was interviewed at three time points over 24 months. A sub-set of 11 caregivers whose eligible children were either partially or non-vaccinated were selected for this sub-analysis. The 5A Taxonomy for root causes of under-vaccination was used to organise the inductively-coded data into categories (awareness, acceptance, access, affordability, and activation) and identify the factors influencing uptake across caregivers. A trajectory analysis was conducted to understand changes in factors over time within each caregiver experience. Caregiver narratives are used to illustrate how the factors influencing uptake were interrelated and changed over time.

Results

Lack of awareness, previous negative experiences with routine childhood immunisations and the burden of getting to the health facility contributed to caregivers initially delaying uptake of the vaccine. Over time concerns about vaccine side effects diminished and anticipated vaccination benefits strongly motivated caregivers to vaccinate their children. Persistent health system barriers (e.g., healthcare provider strikes, vaccine stockouts, negative provider attitudes) meant some children missed the first-dose eligibility window by aging-out.

Conclusions

Caregivers in this study believed the RTS,S/AS01 to be effective and were motivated to have their children vaccinated. Despite these positive perceptions of the malaria vaccine, uptake was substantially hindered by persistent health system constraints. Negative provider attitudes emerged as a powerful deterrent to attending immunisation services and hampered uptake of the vaccine. Strategies that focus on improving interpersonal communication skills among healthcare providers are needed.
The association between dietary amino acid profile and the risk of type 2 diabetes: Ravansar non-communicable disease cohort study
Authors: Najafi Farid , Mohseni Parisa , Pasdar Yahya , Niknam Mahdieh , Izadi Neda
Published: November 2023

Background

Type 2 diabetes (T2D) is one of the most common chronic diseases and the main risk factors for T2D consist of a combination of lifestyle, unhealthy diet, and genetic factors. Amino acids are considered to be a major component of dietary sources for many of the associations between dietary protein and chronic disease. Therefore, this study amied to determine the association between dietary amino acid intakes and the incidence of T2D.

Methods

The present nested case-control study was conducted using data from the Ravansar Non-Communicable Disease (RaNCD) Cohort Study. The information required for this study was collected from individuals who participated in the Adult Cohort Study from the start of the study until September 2023. Over a 6-year follow-up period, data from 113 new T2D cases were available. Four controls were then randomly selected for each case using density sampling. Cases and controls were matched for sex and age at the interview. Food frequency questionnaire (FFQ) was used to collect data related to all amino acids including tryptophan, threonine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, valine, arginine, histidine, alanine, aspartic acid, glutamic acid, glycine, proline, and serine were also extracted. Binary logistic regression was used to estimate the crude and adjusted odds ratio for the risk of T2D.

Results

Using the univariable model, a significant association was found between T2D risk and branched-chain, alkaline, sulfuric, and essential amino acids in the fourth quartile. Accordingly, individuals in the fourth quartile had a 1.81- to 1.87-fold higher risk of developing new T2D than individuals in the lowest quartile (P<0.05). After adjustment for several variables, the risk of developing a new T2D was 2.70 (95% CI: 1.16-6.31), 2.68 (95% CI: 1.16-6.21), 2.98 (95% CI: 1.27-6.96), 2.45 (95% CI: 1.02-5.90), and 2.66 (95% CI: 1.13-6.25) times higher, for individuals in the fourth quartile of branched-chain, alkaline, sulfuric, alcoholic, and essential amino acids compared with those in the lowest quartile, respectively.

Conclusions

The results showed that the risk of developing a new T2D was higher for individuals in the fourth quartile of branched-chain amino acids, alkaline, sulfate, and essential amino acids than in the lower quartile.
Vertebral compression fractures: pain relief, progression and new fracture rate comparing vertebral augmentation with brace
Authors: Gutierrez-Gonzalez Raquel , Royuela A. , Zamarron A.
Published: November 2023

Background

Osteoporotic vertebral compression fracture (VCF) is the third most frequent fragility fracture in the world. Conservative treatment, vertebroplasty, and kyphoplasty are all recognized therapies. However, diagnostic and therapeutic recommendations must be more consistent when comparing clinical guidelines. This study aims to compare the efficacy of vertebral augmentation therapy and conservative management for treating VCFs, the risk of subsequent complications, and the length of hospital stay.

Method

All patients over 50 years old with a diagnosis of thoracic or lumbar VCF without underlying oncological process, treated conservatively or surgically, and consecutively attended at our department from January 2017 to June 2021 were retrospectively selected for analysis. Patients who missed follow-up or died during the first three months were excluded.

Results

A total of 573 cases were selected for analysis. Most patients were treated conservatively (85.3%). Both groups were homogenous regarding epidemiological and clinical features. The median time elapsed to achieve pain relief was significantly lower in the surgical cohort (4.5 vs. 10 weeks, p < 0.001), and the proportion of patients reporting pain at the first outpatient visit was also significantly lower with a vertebral augmentation procedure (p = 0.004). The new fracture rate and the adjacent level rate did not differ significantly when comparing both treatments, whereas the progression of the diagnosed fracture was more frequent in the conservative group (4.8% vs. 29.7%; p < 0.001). The median hospital stay was significantly lower in the conservative group (3 vs. 10 days; p < 0.001).

Conclusion

Surgical treatment (vertebroplasty/kyphoplasty) of VCFs was associated with sooner pain relief without an increased risk of new or adjacent fractures. Moreover, the progression of treated fractures was significantly lower in the surgical cohort. The only unfavorable aspect was the more extended hospital stay compared with the conservative treatment group.
Quality of life after lung cancer surgery: sublobar resection versus lobectomy
Authors: Jiang Shuai , Wang Bao , Zhang Mengzhe , Liu Zuo , Xiao Zengtuan , Gong Jialin , Wang Xiaofei , Zhang Zhenning , Zhang Zhenfa
Published: November 2023

Background

This study aimed to compare the postoperative quality of life (PQOL) between non–small–cell lung cancer (NSCLC) patients who underwent video–assisted thoracoscopic sublobar resection (subsegment, segment, or wedge) and lobectomy. Meanwhile, we developed a PQOL scale for patients with NSCLC after optimization.

Methods

Developing and evaluating the postoperative quality–of–life scale of non–small–cell lung cancer (NSCLC–PQOL) followed by the international principles for developing quality–of–life scale. Therefore, we used the NSCLC–PQOL scale to evaluate the PQOL of patients who underwent different surgeries.

Results

The overall PQOL of patients who underwent video-assisted thoracoscopic lobectomy and sublobar resection gradually worsened from discharge to 3 months postoperatively and progressively improved from three to 6 months postoperatively. And the sublobar resection group showed better PQOL in chest tightness, breath shortness, breathlessness, cough and expectoration than the lobectomy group, and the differences were statistically significant (P < 0.05). The final version of the NSCLC–PQOL contained three dimensions: “signs–symptoms”, “psychological and psychiatric”, and “social–life” dimensions.

Conclusions

The sublobar resection group showed better PQOL in “chest tightness”, “breath shortness”, “breathlessness”, “cough”, and “expectoration” than the lobectomy group. Twenty–two items formed a well–behaved PQOL scale after being validated satisfactorily. The scale was a suitable rating tool for evaluating the NSCLC–PQOL of patients.

Trial registration

As this study was a retrospective study and not a clinical trial, we did not register this study in the Chinese Clinical Trial Registry.
Differential patterns of lifestyle behaviors among low- and high-income postmenopausal women in Korea: a latent class analysis
Authors: Lee Haein , Lee Bo Gyeong , La In Seo
Published: November 2023

Background

Healthy lifestyle behaviors among postmenopausal women are important to prevent chronic diseases and improve health later in life. Heterogeneous lifestyle patterns may exist among postmenopausal women, and socioeconomic status (SES) is a critical determinant of lifestyle behaviors. However, little is known about distinct SES-specific patterns of lifestyle behaviors among postmenopausal women. Thus, this study used latent class analysis to identify subgroups of postmenopausal women with different health behaviors according to income and to examine the predictors of income-specific subgroups.

Methods

We analyzed nationally representative data from the Eighth Korea National Health and Nutrition Examination Survey, collected in 2019 and 2020. We used nine lifestyles (i.e., current smoking and drinking, high-risk drinking, walking, muscle-strengthening exercise, sleep, vegetable and fruit intakes, and weight control efforts). We conducted a multiple-group latent class analysis using monthly household income as a proxy for SES. The monthly household income variable was calculated by standardizing monthly household income by the number of family members and then divided into quintiles. We classified the participants into low- (i.e., Q1 and Q2) and high-income (i.e., Q3, Q4, and Q5) groups.

Results

Although the three-class models best fit the data of low- and high-income groups, we found differential patterns by income: (a) for low-income group, “relatively healthy (RH),” “lowest physical activity, insufficient fruit intake, and no intention to control weight,” and “high-risk drinking and insufficient fruit intake” classes and (b) for high-income group, “RH,” “lowest physical activity,” “high-risk drinking and insufficient fruit intake and sleep” classes. The proportion of the RH class was largest in both groups. However, lifestyle patterns in low-income group showed multiple and unhealthy characteristics than those in high-income group.

Conclusions

This study suggests that different underlying lifestyle patterns exist in postmenopausal women with low- and high-income. To promote healthy behaviors among postmenopausal women, health professionals should develop and apply lifestyle interventions tailored to lifestyle pattern characteristics according to income.
Carboxylic acid reductase-dependent biosynthesis of eugenol and related allylphenols
Authors: Hanko Erik K. R. , Valdehuesa Kris Niño G. , Verhagen Koen J. A. , Chromy Jakub , Stoney Ruth A. , Chua Jeremy , Yan Cunyu , Roubos Johannes A. , Schmitz Joep , Breitling Rainer
Published: November 2023

Background

(Hydroxy)cinnamyl alcohols and allylphenols, including coniferyl alcohol and eugenol, are naturally occurring aromatic compounds widely utilised in pharmaceuticals, flavours, and fragrances. Traditionally, the heterologous biosynthesis of (hydroxy)cinnamyl alcohols from (hydroxy)cinnamic acids involved CoA-dependent activation of the substrate. However, a recently explored alternative pathway involving carboxylic acid reductase (CAR) has proven efficient in generating the (hydroxy)cinnamyl aldehyde intermediate without the need for CoA activation. In this study, we investigated the application of the CAR pathway for whole-cell bioconversion of a range of (hydroxy)cinnamic acids into their corresponding (hydroxy)cinnamyl alcohols. Furthermore, we sought to extend the pathway to enable the production of a variety of allylphenols and allylbenzene.

Results

By screening the activity of several heterologously expressed enzymes in crude cell lysates, we identified the combination of Segniliparus rugosus CAR (SrCAR) and Medicago sativa cinnamyl alcohol dehydrogenase (MsCAD2) as the most efficient enzymatic cascade for the two-step reduction of ferulic acid to coniferyl alcohol. To optimise the whole-cell bioconversion in Escherichia coli, we implemented a combinatorial approach to balance the gene expression levels of SrCAR and MsCAD2. This optimisation resulted in a coniferyl alcohol yield of almost 100%. Furthermore, we extended the pathway by incorporating coniferyl alcohol acyltransferase and eugenol synthase, which allowed for the production of eugenol with a titre of up to 1.61 mM (264 mg/L) from 3 mM ferulic acid. This improvement in titre surpasses previous achievements in the field employing a CoA-dependent coniferyl alcohol biosynthesis pathway. Our study not only demonstrated the successful utilisation of the CAR pathway for the biosynthesis of diverse (hydroxy)cinnamyl alcohols, such as p-coumaryl alcohol, caffeyl alcohol, cinnamyl alcohol, and sinapyl alcohol, from their corresponding (hydroxy)cinnamic acid precursors but also extended the pathway to produce allylphenols, including chavicol, hydroxychavicol, and methoxyeugenol. Notably, the microbial production of methoxyeugenol from sinapic acid represents a novel achievement.

Conclusion

The combination of SrCAR and MsCAD2 enzymes offers an efficient enzymatic cascade for the production of a wide array of (hydroxy)cinnamyl alcohols and, ultimately, allylphenols from their respective (hydroxy)cinnamic acids. This expands the range of value-added molecules that can be generated using microbial cell factories and creates new possibilities for applications in industries such as pharmaceuticals, flavours, and fragrances. These findings underscore the versatility of the CAR pathway, emphasising its potential in various biotechnological applications.
Highly expressed RPLP2 inhibits ferroptosis to promote hepatocellular carcinoma progression and predicts poor prognosis
Authors: Guo Jiaxing , Huang Meiyuan , Deng Shuang , Wang Haiyan , Wang Zuli , Yan Bokang
Published: November 2023

Background

RPLP2, an integral part of ribosomal stalk, plays an important role in the tumorigenesis of various cancers. However, its specific effect on HCC remains elusive.

Methods

TCGA, GTEx, HCCDB, HPA, UALCAN, MethSurv, TISIDB, K–M plotter, FerrDb, RNAactDrug, STRING, Cytoscape and R studio were conducted for bioinformatics analysis. RPLP2 expression level in HCC was verified by IHC and western blot. IHC was used to demonstrate the immune cell infiltration. Functional experiments including CCK8, transwell and colony formation assays, and nude mice xenograft model were performed for in vitro and in vivo validation. Western blot, IHC, CCK8 assay and detection of GSH and lipid ROS were adopted to determine the effect of RPLP2 on the ferroptosis of HCC cells.

Results

Here, we demonstrate that elevated level of RPLP2 is strongly associated with advanced clinicopathologic features, and predicts poor prognosis of HCC patients. Additionally, DNA methylation level of RPLP2 decreases in HCC, and significantly correlates with patients outcome. Moreover, high RPLP2 expression level is linked closely to the unfavorable immune infiltration. Most importantly, RPLP2 positively associates with ferroptosis suppressor GPX4, and inhibition of RPLP2 could lead to the acceleration of ferroptosis to suppress tumor progression of HCC. Last, drug sensitivity analysis predicts many drugs that potentially target RPLP2.

Conclusion

Together, our study reveals previous unrecognized role of RPLP2 in HCC, and provides new regulatory mechanism of ferroptosis, indicating RPLP2 may be a novel therapeutic target for HCC.
The Impact of FGFR3 Alterations on the Tumor Microenvironment and the Efficacy of Immune Checkpoint Inhibitors in Bladder Cancer
Authors: Komura Kazumasa , Hirosuna Kensuke , Tokushige Satoshi , Tsujino Takuya , Nishimura Kazuki , Ishida Mitsuaki , Hayashi Takuo , Ura Ayako , Ohno Takaya , Yamazaki Shogo , Nakamori Keita , Kinoshita Shoko , Maenosono Ryoichi , Ajiro Masahiko , Yoshikawa Yuki , Takai Tomoaki , Tsutsumi Takeshi , Taniguchi Kohei , Tanaka Tomohito , Takahara Kiyoshi , Konuma Tsuyoshi , Inamoto Teruo , Hirose Yoshinobu , Ono Fumihito , Shiraishi Yuichi , Yoshimi Akihide , Azuma Haruhito
Published: November 2023

Background

Currently, only limited knowledge is available regarding the phenotypic association between fibroblast growth factor receptor 3 (FGFR3) alterations and the tumor microenvironment (TME) in bladder cancer (BLCA).

Methods

A multi-omics analysis on 389 BLCA and 35 adjacent normal tissues from a cohort of OMPU-NCC Consortium Japan was retrospectively performed by integrating the whole-exome and RNA-sequence dataset and clinicopathological record. A median follow-up duration of all BLCA cohort was 31 months.

Results

FGFR3 alterations (aFGFR3), including recurrent mutations and fusions, accounted for 44% of non-muscle invasive bladder cancer (NMIBC) and 15% of muscle-invasive bladder cancer (MIBC). Within MIBC, the consensus subtypes LumP was significantly more prevalent in aFGFR3, whereas the Ba/Sq subtype exhibited similarity between intact FGFR3 (iFGFR3) and aFGFR3 cases. We revealed that basal markers were significantly increased in MIBC/aFGFR3 compared to MIBC/iFGFR3. Transcriptome analysis highlighted TIM3 as the most upregulated immune-related gene in iFGFR3, with differential immune cell compositions observed between iFGFR3 and aFGFR3. Using EcoTyper, TME heterogeneity was discerned even within aFGFR cases, suggesting potential variations in the response to checkpoint inhibitors (CPIs). Among 72 patients treated with CPIs, the objective response rate (ORR) was comparable between iFGFR3 and aFGFR3 (20% vs 31%; p = 0.467). Strikingly, a significantly higher ORR was noted in LumP/aFGFR3 compared to LumP/iFGFR3 (50% vs 5%; p = 0.022). This trend was validated using data from the IMvigor210 trial. Additionally, several immune-related genes, including IDO1, CCL24, IL1RL1, LGALS4, and NCAM (CD56) were upregulated in LumP/iFGFR3 compared to LumP/aFGFR3 cases.

Conclusions

Differential pathways influenced by aFGFR3 were observed between NMIBC and MIBC, highlighting the upregulation of both luminal and basal markers in MIBC/aFGFR3. Heterogeneous TME was identified within MIBC/aFGFR3, leading to differential outcomes for CPIs. Specifically, a favorable ORR in LumP/aFGFR3 and a poor ORR in LumP/iFGFR3 were observed. We propose TIM3 as a potential target for iFGFR3 (ORR: 20%) and several immune checkpoint genes, including IDO1 and CCL24, for LumP/iFGFR3 (ORR: 5%), indicating promising avenues for precision immunotherapy for BLCA.
Triplet‐drug chemotherapy combined with anti‐EGFR antibody as an effective therapy for patients with initially unresectable metastatic colorectal cancer: a meta-analysis
Authors: Tian Muyou , Li Huifen , Dong Wenjing , Li Yuhong , Jiang Ting , Lv Yanhua , Zeng Jianxiong , Jiang Xiaomei , Yin Zhaofeng , Xiao Jianjun
Published: November 2023

The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet‐drug regimen combined with anti‐EGFR antibody in patients with initially unresectable metastatic colorectal cancer (mCRC). A systematic literature search was performed in PubMed Publisher. Studies evaluating FOLFOXIRI combine with panitumumab or cetuximab as the therapy for initially unresectable mCRC were included. The primary outcome was objective response rate (ORR) and rate of R0 resections. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and grades 3 or 4 adverse events. R software (version 4.0.2) and RevMan (version 5.3) were used to analyze the extracted data. The studies included were published between 2010 and 2021, involving four single-arm phase II trials and two randomized phase II trials. A total of 6 studies with 282 patients were included. The data showed a significant benefit for the FOLFOXIRI + anti-EGFR antibody arm compared with FOLFOXIRI arm (RR 1.33; 95% CI, 1.13–1.58; I2 = 0%, P < 0.05). The pooled ORR and pooled rate of R0 resection in patients who receiving FOLFOXIRI + anti-EGFR antibody were 85% (95% CI, 0.78–0.91; I2 = 58%) and 42% (95% CI, 0.32–0.53; I2 = 62%), respectively. The range of median PFS between all the six studies was 9.5–15.5 months, with weighted pooled median PFS mean 11.7 months. The range of median OS between all the four studies was 24.7–37 months, with weighted pooled median PFS mean 31.9 months. The common grades 3 and 4 adverse events were diarrhea and neutropenia. Our findings show that triplet-drug chemotherapy (FOLFOXIRI) combined with anti-EGFR antibody (panitumumab or cetuximab) represents a very effective therapeutic combination associated with a significant ORR and R0 rection rate for patients with molecularly unselected and surgically unresectable metastatic CRC.
Improved surgical exposure and early clinical outcomes using a femoral-release-first technique in direct anterior approach during total hip arthroplasty
Authors: Xiong Hua-zhang , Yang Li-dan , Bao Gang , Peng Jia-chen , Liu Zhi-hong
Published: November 2023

Background

Total hip arthroplasty (THA) performed using the direct anterior approach (DAA) has demonstrated favourable early-, mid-, and long-term outcomes. However, the traditional femoral release technique remains technically demanding and is associated with challenges and a heightened risk of complications. This study aimed to compare the clinical outcomes of patients who underwent THA with DAA performed using either the femoral-release-first (FRF) or the traditional approach (TA) strategy.

Methods

A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 106 patients between 2018 and 2019. The patients were categorised into two groups: FRF (44 hips) and TA (69 hips).

Results

The FRF group showed a reduced operative time, haemoglobin (Hb) drop, postoperative hospital stay, and more optimal acetabular cup anteversion angles. Furthermore, during the first 2 months postoperatively, the FRF group demonstrated superior visual analogue scale, Harris Hip, and Oxford Hip scores. In the TA group, two hips experienced greater trochanter fractures, and one experienced delayed incision healing.

Conclusions

Compared with the TA, employing the FRF strategy during THA with DAA resulted in improved outcomes within the first 2 months postoperatively and comparable functional recovery beyond this period. The FRF method exhibited advantages such as favourable acetabular exposure and alignment and a reduced risk of complications. Therefore, the FRF strategy may be a favourable option.
Comparing acute normovolumic hemodilution with autologous platelet-rich plasma for blood preservation during aortic surgery : study protocol for a randomized controlled clinical trial
Authors: Zhu Dan , Li Yu , Tian A-yong , Wang Hong-nan
Published: November 2023

Background

Both acute normovolumic hemodilution (ANH) and autologous platelet-rich plasma (aPRP) have been demonstrated blood-protective effects in cardiac aortic surgery; however, the efficacies of the two methods have not been compared. This study aims to compare the effects of aPRP and ANH prior to aortic surgery on postoperative bleed and other outcomes.

Methods and analysis

This is a prospective, single-center, double-blind controlled clinical trial including 160 patients randomized 1:1 to receive aPRP (test group) or autologous whole blood (ANH, control group). The primary objective is to compare the drainage volumes in the two groups at 24, 48, and 72 h postoperatively. Secondary outcomes include input of allogeneic blood and blood products and durations of aortic block, extracorporeal circulation, deep hypothermic arrest of circulation, tracheal extubation, hospital stay, requirement for secondary surgical hemostasis, and application of intra-aortic balloon pump or extracorporeal membrane oxygenation in the two groups. In addition, heart rate, systolic blood pressure, diastolic blood pressure, central venous pressure, and thromboelastography recorded before blood reservation (T1), after blood reservation (T2), before blood transfusion (T3), and after the blood is returned (T4) to the transfusion will be compared between the two groups of patients.

Discussion

This study will demonstrate if the use of aPRP could reduce the risk of bleeding after aortic surgery compared with ANH. The results are expected to have practical clinical applications in terms of more effective blood protection and shorter hospital stay.

Trial registration

This study was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the ID ChiCTR 1900023351.Registered on May 23, 2019.

Trial status

Recruiting start date: July 1, 2019; expected recruiting end date: July 1, 2024

Version number and date: Version 2 of 05-04-2019
Hemophilia A and factor V deficiency in a girl with Turner syndrome: a case report
Authors: Al khudari Rawan , Batesh Duaa , Habash Roaa , Hamdn Othman
Published: November 2023

Background

Hemophilia is an X-linked, recessive inherited disease caused by a defect or deficiency of one of the coagulation factors (VIII or IX). It is considered a rare disease in females. One of the reasons that hemophilia affects females is Turner syndrome. Hemophilia with Turner syndrome is a very rare case, but the combination of Turner syndrome, hemophilia, and factor V deficiency is an isolated case that has never been recorded in the medical literature.

Case presentation

In our case, a 5-year-old Syrian girl presented with hemorrhage of gum, epistaxis, and short stature. The lab tests showed: prolonged activated partial thromboplastin time and prothrombin time with deficiency of factor V (1%) and factor VIII (1%). We diagnosed hemophilia A with factor V deficiency. In addition to short stature, the patient was noted to have spaced nipples and winged neck. We performed karyotyping that showed deletion of one X chromosome (45X0), Turner syndrome. There is no family history of hemophilia or any other genetic disease.

Conclusions

In females affected with hemophilia, karyotyping should be performed. It is very important not to exclude the possibility of a combination of deficiency of more than one clotting factor, and to note that deficiency of more than one factor does not necessarily increase the severity of bleeding compared with deficiency of a single factor.
Electrical impedance myography detects dystrophin-related muscle changes in mdx mice
Authors: Hiyoshi Tetsuaki , Zhao Fuqiang , Baba Rina , Hirakawa Takeshi , Kuboki Ryosuke , Suzuki Kazunori , Tomimatsu Yoshiro , O’Donnell Patricio , Han Steve , Zach Neta , Nakashima Masato
Published: November 2023

Background

The lack of functional dystrophin protein in Duchenne muscular dystrophy (DMD) causes chronic skeletal muscle inflammation and degeneration. Therefore, the restoration of functional dystrophin levels is a fundamental approach for DMD therapy. Electrical impedance myography (EIM) is an emerging tool that provides noninvasive monitoring of muscle conditions and has been suggested as a treatment response biomarker in diverse indications. Although magnetic resonance imaging (MRI) of skeletal muscles has become a standard measurement in clinical trials for DMD, EIM offers distinct advantages, such as portability, user-friendliness, and reduced cost, allowing for remote monitoring of disease progression or response to therapy. To investigate the potential of EIM as a biomarker for DMD, we compared longitudinal EIM data with MRI/histopathological data from an X-linked muscular dystrophy (mdx) mouse model of DMD. In addition, we investigated whether EIM could detect dystrophin-related changes in muscles using antisense-mediated exon skipping in mdx mice.

Methods

The MRI data for muscle T2, the magnetic resonance spectroscopy (MRS) data for fat fraction, and three EIM parameters with histopathology were longitudinally obtained from the hindlimb muscles of wild-type (WT) and mdx mice. In the EIM study, a cell-penetrating peptide (Pip9b2) conjugated antisense phosphorodiamidate morpholino oligomer (PPMO), designed to induce exon-skipping and restore functional dystrophin production, was administered intravenously to mdx mice.

Results

MRI imaging in mdx mice showed higher T2 intensity at 6 weeks of age in hindlimb muscles compared to WT mice, which decreased at ≥ 9 weeks of age. In contrast, EIM reactance began to decline at 12 weeks of age, with peak reduction at 18 weeks of age in mdx mice. This decline was associated with myofiber atrophy and connective tissue infiltration in the skeletal muscles. Repeated dosing of PPMO (10 mg/kg, 4 times every 2 weeks) in mdx mice led to an increase in muscular dystrophin protein and reversed the decrease in EIM reactance.

Conclusions

These findings suggest that muscle T2 MRI is sensitive to the early inflammatory response associated with dystrophin deficiency, whereas EIM provides a valuable biomarker for the noninvasive monitoring of subsequent changes in skeletal muscle composition. Furthermore, EIM reactance has the potential to monitor dystrophin-deficient muscle abnormalities and their recovery in response to antisense-mediated exon skipping.
Minimize average tasks processing time in satellite mobile edge computing systems via a deep reinforcement learning method
Authors: Pang Shanchen , Zheng Jianyang , Wang Min , Qiao Sibo , He Xiao , Gao Changnan
Published: November 2023

Recently, the development of Low Earth Orbit (LEO) satellites and the advancement of the Mobile Edge Computing (MEC) paradigm have driven the emergence of the Satellite Mobile Edge Computing (Sat-MEC). Sat-MEC has been developed to support communication and task computation for Internet of Things (IoT) Mobile Devices (IMDs) in the absence of terrestrial networks. However, due to the heterogeneity of tasks and Sat-MEC servers, it is still a great challenge to efficiently schedule tasks in Sat-MEC servers. Here, we propose a scheduling algorithm based on the Deep Reinforcement Learning (DRL) method in the Sat-MEC architecture to minimize the average task processing time. We consider multiple factors, including the cooperation between LEO satellites, the concurrency and heterogeneity of tasks, the dynamics of LEO satellites, the heterogeneity of the computational capacity of Sat-MEC servers, and the heterogeneity of the initial queue for task computation. Further, we use the self-attention mechanism to act as a Q-network to extract high-dimensional dynamic information of tasks and Sat-MEC servers. In this work, we model the Sat-MEC environment simulation at the application level and propose a DRL-based task scheduling algorithm. The simulation results confirm the effectiveness of our proposed scheduling algorithm, which reduces the average task processing time by 22.1$$\%$$
%
, 30.6$$\%$$
%
, and 41.3$$\%$$
%
, compared to the genetic algorithm(GA), the greedy algorithm, and the random algorithm, respectively.
Subthreshold opioid use disorder prevention (STOP) trial: a cluster randomized clinical trial: study design and methods
Authors: Liebschutz Jane M. , Subramaniam Geetha A. , Stone Rebecca , Appleton Noa , Gelberg Lillian , Lovejoy Travis I. , Bunting Amanda M. , Cleland Charles M. , Lasser Karen E. , Beers Donna , Abrams Catherine , McCormack Jennifer , Potter Gail E. , Case Ashley , Revoredo Leslie , Jelstrom Eve M. , Kline Margaret M. , Wu Li-Tzy , McNeely Jennifer
Published: November 2023

Background

Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD.

Methods

The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population.

Discussion

Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population.

Trial Registration: Clinicaltrials.gov, identifier NCT04218201, January 6, 2020.
CD72, a new immune checkpoint molecule, is a novel prognostic biomarker for kidney renal clear cell carcinoma
Authors: Tian Lv , Wang Yiming , Zhang Zhiyuan , Feng Xuechao , Xiao Fengjun , Zong Minru
Published: November 2023

Background

The incidence and mortality of clear cell carcinoma of the kidney increases yearly. There are limited screening methods and advances in treating kidney renal clear cell carcinoma (KIRC). It is important to find new biomarkers to screen, diagnose and predict the prognosis of KIRC. Some studies have shown that CD72 influences the development and progression of colorectal cancer, nasopharyngeal cancer, and acute lymphoid leukemia. However, there is a lack of research on the role of CD72 in the pathogenesis of KIRC. This study aimed to determine whether CD72 is associated with the prognosis and immune infiltration of KIRC, providing an essential molecular basis for the early non-invasive diagnosis and immunotherapy of KIRC.

Methods

Using TCGA, GTE, GEO, and ImmPort databases, we obtained the differentially expressed mRNA (DEmRNA) associated with the prognosis and immunity of KIRC patients. We used the Kruskal–Wallis test to identify clinicopathological parameters associated with target gene expression. We performed univariate and multivariate COX regression analyses to determine the effect of target gene expression and clinicopathological parameters on survival. We analyzed the target genes' relevant functions and signaling pathways through enrichment analysis. Finally, the correlation of target genes with tumor immune infiltration was explored by ssGSEA and Spearman correlation analysis.

Results

The results revealed that patients with KIRC with higher expression of CD72 have a poorer prognosis. CD72 was associated with the Pathologic T stage, Pathologic stage, Pathologic M stage, Pathologic N stage, Histologic grade in KIRC patients, Laterality, and OS event. It was an independent predictor of the overall survival of KIRC patients. Functional enrichment analysis showed that CD72 was significantly enriched in oncogenic and immune-related pathways. According to ssGSEA and Spearman correlation analysis, CD72 expression was significantly associated with tumor immune cells and immune checkpoints.

Conclusion

Our study suggests that CD72 is associated with tumor immunity and may be a biomarker relevant to the diagnosis and prognosis of KIRC patients.
Challenges of digitization in the social economy in times of pandemic: the evolution of online presence and e-commerce in agri-food cooperatives
Authors: Cristobal-Fransi Eduard , Daries Natalia , Cardona José Ramón , Del Río-Rama María de la Cruz
Published: November 2023

Online presence is essential for companies operating in the social economy. The health crisis resulting from Covid-19 has reinforced the need to access the Internet and develop online commerce. This paper analyses the online presence of Catalan agricultural cooperatives, their level of maturity in the development of e-commerce and the changes that have occurred during the years characterized by the restrictions resulting from the pandemic. To this end, content analysis and the eMICA methodology (Extended Model of Internet Commerce Adoption) were used to study the websites of various Catalan agricultural cooperatives. The model was applied to 104 cooperatives with an online presence in 2022, and the results were compared to a previous study conducted in 2018. The results indicate that although cooperatives have improved their online presence, especially in relation to online commerce, there is still much room for optimal interaction with their target audience. The pandemic and resulting restrictions on mobility forced a rapid deployment of e-commerce, often without sufficiently developing the interactivity of websites. The circumstances within the sample are varied, with wine cooperatives being the most mature in their use of e-commerce compared to olive oil and fruit cooperatives. The latter are the most deficient in their online presence and e-commerce development.
Host species and habitat shape fish-associated bacterial communities: phylosymbiosis between fish and their microbiome
Authors: Sadeghi Javad , Chaganti Subba Rao , Johnson Timothy B. , Heath Daniel D.
Published: November 2023

Background

While many studies have reported that the structure of the gut and skin microbiota is driven by both species-specific and habitat-specific factors, the relative importance of host-specific versus environmental factors in wild vertebrates remains poorly understood. The aim of this study was to determine the diversity and composition of fish skin, gut, and surrounding water bacterial communities (hereafter referred to as microbiota) and assess the extent to which host habitat and phylogeny predict microbiota similarity. Skin swabs and gut samples from 334 fish belonging to 17 species were sampled in three Laurentian Great Lakes (LGLs) habitats (Detroit River, Lake Erie, Lake Ontario). We also collected and filtered water samples at the time of fish collection. We analyzed bacterial community composition using 16S metabarcoding and tested for community variation.

Results

We found that the water microbiota was distinct from the fish microbiota, although the skin microbiota more closely resembled the water microbiota. We also found that environmental (sample location), habitat, fish diet, and host species factors shape and promote divergence or convergence of the fish microbiota. Since host species significantly affected both gut and skin microbiota (separately from host species effects), we tested for phylosymbiosis using pairwise host species phylogenetic distance versus bacterial community dissimilarity. We found significant phylogenetic effects on bacterial community dissimilarity, consistent with phylosymbiosis for both the fish skin and gut microbiota, perhaps reflecting the longstanding co-evolutionary relationship between the host species and their microbiomes.

Conclusions

Analyzing the gut and skin mucus microbiota across diverse fish species in complex natural ecosystems such as the LGLs provides insights into the potential for habitat and species-specific effects on the microbiome, and ultimately the health, of the host.
Psychometric properties of an Arabic translation of the shortest version of the Central Religiosity Scale (CRS-5) in a sample of young adults
Authors: Fekih-Romdhane Feten , El Tawil Nathalie , El Zouki Christian-Joseph , Jaalouk Karolina , Obeid Sahar , Hallit Souheil
Published: November 2023

Background

There is a dearth of research on religiosity in Arabic-speaking populations, partly due to a lack of universal, standardized and valid instruments to assess this construct. We sought through this study to establish the psychometric properties of an Arabic translation of the shortest version of the Central Religiosity Scale (CRS-5), a widely used measure of religiosity that can be applicable to most religious traditions, thus allowing for worldwide cultural and trans-religious comparisons.

Method

A total of 352 Lebanese young adults enrolled in this study with a mean age of 25.08 years (SD = 9.25) and 73.3% women. The forward-backward method was adopted to translate the original English version of the CRS-5 to Arabic.

Results

We ran an Exploratory Factor Analysis for the CRS-5 to test whether the expected dimensionality is suitable for the subsequent Confirmatory Factor Analysis (CFA). The model found replicates the originally proposed five items and one-factor model. Our findings demonstrated that the Arabic CRS-5 achieved good levels of composite reliability, with a McDonald’s ω coefficient of .85. A multi-group CFA was modelled for the examination of measurement invariance of the Arabic CRS-5 across gender at the metric, configural, and scalar levels. Between-gender comparisons revealed no significant differences between males and females regarding CRS-5 scores. Finally, we found that religiosity was positively correlated with positive mental health aspects (i.e., social support) and inversely correlated with negative mental health aspects (i.e., suicidal ideation, depression, social anxiety and entrapment); thus attesting for the convergent validity of the CRS-5 as a measure of centrality of religiosity.

Conclusion

Pending further validations with larger and more representative populations, we preliminarily suggest that the Arabic CRS-5 is psychometrically sound, and can be recommended for use for research and clinical purposes in Arabic-speaking people of various religions and cultures.
The optimal dose of mobilisation therapy in the ICU: a prospective cohort study
Authors: Lorenz Marco , Fuest Kristina , Ulm Bernhard , Grunow Julius J. , Warner Linus , Bald Annika , Arsene Vanessa , Verfuß Michael , Daum Nils , Blobner Manfred , Schaller Stefan J.
Published: November 2023

Background

This study aimed to assess the impact of duration of early mobilisation on survivors of critical illness. The hypothesis was that interventions lasting over 40 min, as per the German guideline, positively affect the functional status at ICU discharge.

Methods

Prospective single-centre cohort study conducted in two ICUs in Germany. In 684 critically ill patients surviving an ICU stay > 24 h, out-of-bed mobilisation of more than 40 min was evaluated.

Results

Daily mobilisation ≥ 40 min was identified as an independent predictor of an improved functional status upon ICU discharge. This effect on the primary outcome measure, change of Mobility-Barthel until ICU discharge, was observed in three different models for baseline patient characteristics (average treatment effect (ATE), all three models p < 0.001). When mobilisation parameters like level of mobilisation, were included in the analysis, the average treatment effect disappeared [ATE 1.0 (95% CI − 0.4 to 2.4), p = 0.16].

Conclusions

A mobilisation duration of more than 40 min positively impacts functional outcomes at ICU discharge. However, the maximum level achieved during ICU stay was the most crucial factor regarding adequate dosage, as higher duration did not show an additional benefit in patients with already high mobilisation levels.

Trial registration: Prospective Registry of Mobilization-, Routine- and Outcome Data of Intensive Care Patients (MOBDB), NCT03666286. Registered 11 September 2018—retrospectively registered,

https://classic.clinicaltrials.gov/ct2/show/NCT03666286.
Efficacy of small back optic zone design on myopia control for corneal refractive therapy (CRT): a one-year prospective cohort study
Authors: Li Xuewei , Zuo Lili , Zhao Heng , Hu Jie , Tang Tao , Wang Kai , Li Yan , Zhao Mingwei
Published: November 2023

Background

To investigate the control effect on the axial length elongation using corneal refractive therapy (CRT) with different optical zone diameters (BOZDs). We also sought to compare the difference in higher-order aberrations (HOAs), treatment zone (TZ) size and Zernike defocus coefficient with different BOZDs and seek the optimal parameter for predicting axial elongation.

Methods

This prospective cohort study included 7- to 14-year-olds fitted with orthokeratology (ortho-K) lenses of 5-mm (5-mm group) or 6-mm BOZD (6-mm group). Axial length (AL), corneal topography, HOAs and Zernike defocus coefficient were obtained at baseline, and 1, 3, 6, 9 and 12 months follow-up visits. Multivariate regression analyses were used to explore the association between AL change and ocular biometric parameters. Receiver operating characteristic (ROC) curve analysis was used to determine the best diagnostic value for AL change in ocular biometric parameters.

Results

In total, 301 participants completed the one-year follow-up. The mean AL change in the 5-mm group (0.13 ± 0.18 mm) was less than that in the 6-mm group (0.27 ± 0.15 mm) at the 12 months visit. The TZ size and decentration were smaller, while the Zernike defocus coefficient and HOAs were higher in the 5-mm group (all P < 0.05). Older age and smaller TZ size were protective factors against AL elongation in multiple regression. In predicting AL elongation, TZ diameter yielded an area under the ROC curve of 0.684 with a cut-off value of 3.82 mm.

Conclusion

The 5-mm group showed 0.14 mm (51.8%) less axial elongation than the 6-mm group. The 5-mm BOZD produced a smaller TZ size, higher Zernike defocus coefficient and higher HOA after reshaping of the cornea. TZ size was the best predictor of AL elongation. TZ diameter less than 3.82 mm may lead to AL elongation less than 0.2 mm in one year.