bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of different antithrombotic agents in combination with tranexamic acid for venous thromboembolism prophylaxis and blood management after total knee replacement: a prospective randomized study
Authors: Zhou Li-Bo , Wang Chao-Chao , Zhang Lan-Tao , Wu Tao , Zhang Guo-Qiu 
Published: January 2023

AbstractBackgroundTranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA.MethodsA total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate.ResultsThe average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml,P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL,P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%,P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%,P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups.ConclusionUnder the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.
Applications, benefits and challenges of telehealth in India during COVID-19 pandemic and beyond: a systematic review
Authors: Rajkumar Eslavath , Gopi Aswathy , Joshi Aditi , Thomas Aleena Elizabeth , Arunima N. M. , Ramya Gosetty Sri , Kulkarni Prachi , Rahul P. , George Allen Joshua , Romate John , Abraham John 
Published: January 2023

AbstractBackgroundIndia, the seventh-largest country in the world and the second-most populated faces enormous challenges when it comes to healthcare. The country’s healthcare system was close to collapse due to the detrimental effects of the COVID-19 pandemic. Telehealth, which enables treating patients remotely, played a critical role during these challenging times. This systematic review investigates in detail the role of telehealth during COVID-19 and its application beyond the pandemic.MethodsDatabase searches on PubMed, Scopus, Science Direct and Web of Science were carried out for studies published on telehealth, and articles were included if they focused on any audio or video telehealth consultation during the pandemic in India. Findings were synthesised into three main themes: applications, benefits and challenges of telehealth services. Methodological quality was assessed using JBI critical appraisal tools.ResultsThe initial search on databases yielded 1143 articles. Of those, 19 met the eligibility criteria. Findings highlight the effective utilisation of telehealth across multiple medical specialities. Although insufficient technological infrastructure and other barriers due to the virtual consultation challenge the successful implementation of telehealth in India, it has the potential to bridge the rural-urban healthcare divide with cost-effective and easily accessible services.ConclusionHigh patient/provider satisfaction underscores the need to integrate telehealth into routine healthcare practices in the country. However, the review urges the government and healthcare practitioners to address the telehealth challenges with prime importance to ensure quality healthcare throughout the nation even after the pandemic.
First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations
Authors: Wang Xuan , Luo Zhiguo , Chen Jing , Chen Yu , Ji Dongmei , Fan Li , Chen Ling , Zhao Qian , Hu Pei , Sun Peng , Jia Zhongwei , Guo Jun , Si Lu 
Published: January 2023

Abstract

Background
HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.

Methods
This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5–18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.

Results
Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months.

Conclusions
The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations.

Trial registration
Trial registration ClinicalTrials.gov number: NCT03973151.
In vitro assessment of PEG-6000 coated-ZnO nanoparticles: modulating action to the resisted antibiotic activity against APEC
Authors: Badry Aml , Ibrahim Awad Abd El Hafez , Said Mohamed I. , Nasr Asmaa A. E. , Mohamed Moemen A. , Hassan Ahmed K. , Safwat Marwa M. 
Published: January 2023

Abstract
Background
Avian pathogenic Escherichia coli (APEC) are considered a growing health problem to both poultry and the public, particularly due to its multi-drug resistance. Zinc oxide nanoparticles (ZnO-NPs) are a promising multi-benefit candidate. This study focused on boosting the antimicrobial effect of the chemically synthesized ZnO-NPs using Polyethylene glycol-6000 (PEG-6000) and evaluating their potential to recover the sensitivity of Florfenicol and Streptomycin-resistant APEC to these drugs in a concentration range of 0.1–0.4 mg/mL. Four samples of ZnO-NPs were formulated and tested microbiologically.

Results
The physicochemical characterization showed well-crystallized spherical in situ synthesized ZnO-NPs using PEG-6000 (surfactant) and ethanol (co-surfactant) of ∼19–67 nm particle size after coating with PEG-6000 molecules. These ZnO-NPs demonstrated a strong concentration-dependent antibacterial effect against multidrug-resistant APEC strains, with a minimum inhibitory concentration of 0.1 mg/mL, Combining PEG-6000 coated in situ synthesized ZnO-NPs and Florfenicol induced 60% high sensitivity (30 mm inhibitory-zone), 30% intermediate sensitivity, and 10% resistance against APEC strains. The combination with Streptomycin revealed 50% high sensitivity, 30% intermediate sensitivity, and 20% resistance with a 20 mm maximum zone of inhibition using agar well diffusion test.

Conclusion
In situ preparation of ZnO-NPs using PEG-6000 and ethanol followed by coating with PEG-6000 enhanced its antibacterial activity in minimum inhibitory concentration and regained the efficacy of Florfenicol and Streptomycin against APEC, referring to a non-antibiotic antimicrobial alternative and an effective combination regimen against multidrug-resistant APEC E. coli in veterinary medicine.
Intimate communications within the tumor microenvironment: stromal factors function as an orchestra
Authors: Cheng Bing , Yu Qiang , Wang Wenyu 
Published: January 2023

AbstractExtensive studies of the tumor microenvironment (TME) in the last decade have reformed the view of cancer as a tumor cell-centric disease. The tumor microenvironment, especially termed the "seed and soil" theory, has emerged as the key determinant in cancer development and therapeutic resistance. The TME mainly consists of tumor cells, stromal cells such as fibroblasts, immune cells, and other noncellular components. Within the TME, intimate communications among these components largely determine the fate of the tumor. The pivotal roles of the stroma, especially cancer-associated fibroblasts (CAFs), the most common component within the TME, have been revealed in tumorigenesis, tumor progression, therapeutic response, and tumor immunity. A better understanding of the function of the TME sheds light on tumor therapy. In this review, we summarize the emerging understanding of stromal factors, especially CAFs, in cancer progression, drug resistance, and tumor immunity with an emphasis on their functions in epigenetic regulation. Moreover, the importance of epigenetic regulation in reshaping the TME and the basic biological principles underpinning the synergy between epigenetic therapy and immunotherapy will be further discussed.
Cochlear sparing in LINAC-based radiosurgery for vestibular schwannoma: a dosimetric comparison of dynamic conformal arc, IMRT and VMAT treatment plans
Authors: Khong Jeremy , Govindaraj Ramkumar , Ramm Daniel , Edwards Suzanne , Roos Daniel 
Published: January 2023

Abstract
Background
Stereotactic radiosurgery (SRS) is the preferred treatment for vestibular schwannoma (VS) in patients with preserved hearing and tumour diameter < 3 cm. Emerging evidence suggests restricting cochlear dose could preserve hearing. This retrospective replanning study aims to compare dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for superiority of cochlear dose sparing without compromising tumour coverage.

Methods
Eligibility criteria included sporadic VS, serviceable hearing and availability of CT and MRI for planning. The original gross tumour volume and brainstem OAR volume were retained; the cochlea was newly contoured on the planning CT scan (bone window). Each case was replanned using the three above techniques, prescribing 12 Gy to the 80% isodose line. No dose constraint was applied to the cochlea.

Results
Eighteen patients were replanned. Mean tumour volume was 2.25 cc. Tumour coverage and tumour mean dose (DCAT: 14.2, IMRT: 14.6, VMAT: 14.5 Gy) were comparable. Paddick and RTOG conformity indices were better for DCAT (0.66 and 1.6) and VMAT (0.69 and 1.5) compared to IMRT (0.56 and 1.9). DCAT had superior gradient index (3.0) compared to VMAT (3.4) and IMRT (3.4). VMAT delivered the lowest mean brainstem maximum dose (8.3 Gy) and decreased the mean cochlear dose (3.4 Gy) by 2.3 and 2.1 Gy, and the mean cochlear maximum dose (3.6 Gy) by 2.4 and 2.5 Gy relative to DCAT and IMRT, respectively.

Conclusion
LINAC-based SRS treatment using VMAT can achieve better cochlear dose sparing than DCAT or IMRT while maintaining tumour coverage.
The effectiveness of psychoeducation and problem-solving on depression and treatment adherence in adolescents living with HIV in Botswana: an exploratory clinical trial
Authors: Olashore Anthony A. , Paruk Saeeda , Ogunwale Adegboyega , Ita Mkpang , Tomita Andrew , Chiliza Bonginkosi 
Published: January 2023

Abstract
Background
This study aimed to explore the effectiveness of psychological interventions (PI): psychoeducation, problem-solving, and rehearsal strategies on depression and adherence in HIV-infected adolescents in Botswana.

Methods
Fifty adolescents living with HIV were randomized into control (n = 25) and intervention groups (n = 25), the latter being exposed to five weeks of PI sessions. The PHQ-9 and visual analog scale (VAS) were used to measure the outcomes: depression and adherence at pre-intervention, 5- and 24 weeks post-intervention.

Results
The participants’ mean age (SD) was 17.38 years (1.1), the two groups being similar in socio-demographic variables: gender (χ2 = 2.22; p = 0.135) and age (U = 285, z =  − 0.55, p = 0.579). The intervention group scored significantly lower on depressive symptoms (PHQ-9 [F (1,50) = 12.0, p = 0.001, ƞp2 = 0.20]) and higher on adherence score (VAS [F (1,50) = 13.5, p = 0.001, ƞp2 = 0.22]) than the control group after 5 weeks. The post-hoc analysis showed that the significant improvements in depressive symptoms (z =  − 4.03, p < 0.01, r [effect size] = 0.88) and adherence (z =  − 4.05, p < 0.01, r = 0.88) at post-test in the intervention group were maintained at 24 weeks. This project was registered with ClinicalTrials.gov (NCT05482217).

Conclusion
The 5-week PI showed promising effectiveness in addressing depression and adherence in adolescents living with HIV in Botswana.
Common Clinical Trial Amendments, why they are submitted and how they can be avoided: a mixed methods study on NHS UK Sponsored Research (Amendments Assemble)
Authors: Joshi Shivam 
Published: January 2023

Abstract
Background
Amendments are changes made to a clinical trial after it has received regulatory approval. An amendment can take a significant amount of time and resources to develop, review and implement at participating sites. This can affect the efficient delivery of clinical trials and potentially contribute to research waste. This study aimed to establish what the most common amendments are, why they are submitted, and what, if anything, can be done to avoid them.

Methods
An explanatory sequential mixed methods design was employed. The first strand involved a content analysis on a sample of amendments, submitted in trials sponsored by a University Hospital NHS Trust between September 2009 and March 2020, to establish the most common changes and reasons for amendments. The second strand involved thematically analysing semi-structured interviews with trial stakeholders to explore their views on the reasons underpinning the submission of amendments, and the potential for efficiencies that could prevent avoidable amendments.

Results
Two hundred forty-two approved amendments were examined from 53 clinical research studies. The ‘Addition of sites’ was the most common amendment change, and the most common reason for amendments was ‘To achieve the trial’s recruitment target’. The root causes for avoidable amendments identified by the 11 interviewees included the following: ‘Rushing the initial application knowing an amendment will be needed later’, ‘Not involving all the right people to input’ at the start of the trial, and ‘Realising it’s not feasible in practice when delivering the trial’. Missing regulatory checks following an onerous and error-prone application process were also identified as the cause of some amendments.

Conclusions
Trials need to be critically reviewed by various stakeholders and have sufficient time allocated to planning and feasibility assessments to avoid some amendments. This may improve clinical trial efficiency, to benefit the trial participants, researchers, funders, sponsors, and regulatory bodies, and potentially bring new treatments to patients faster.
Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression
Authors: Sokolov Aleksandr V. , Manu Diana-Maria , Nordberg Didi O. T. , Boström Adrian D. E. , Jokinen Jussi , Schiöth Helgi B. 
Published: January 2023

AbstractDepression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 andn = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521,pvalue ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041,pvalue ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40,pvalue ~ 0.089) and trend for association with depression treatment (n = 377,pvalue ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374,pvalue ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (pvalue ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237,pvalue ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD14+cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation atMAD1L1is important for psychiatric health as supported by several independent cohorts.
Optimization of bioethanol production from sugarcane molasses by the response surface methodology using Meyerozyma caribbica isolate MJTm3
Authors: Hawaz Estifanos , Tafesse Mesfin , Tesfaye Anteneh , Kiros Solomon , Beyene Dereje , Kebede Gessesse , Boekhout Teun , Groenwald Marizeth , Theelen Bart , Degefe Ayantu , Degu Sisay , Admasu Alene , Hunde Biru , Muleta Diriba 
Published: January 2023

Abstract
Purpose
Yeast strains tolerant to a wide range of stress conditions are needed for the production of bioethanol from substrates rich in sugar. In our earlier research findings, Meyerozyma caribbica isolate MJTm3 (OM329077) demonstrated remarkable stress tolerance and fermentative activity. The present study aimed to optimize six fermentation parameters to generate conducive fermentation conditions for ethanol production by M. caribbica isolate MJTm3.

Method
The response surface method (RSM) based on central composite design (CCD) was employed to optimize process conditions for higher bioethanol yield. The optimization process was carried out based on six independent parameters, namely temperature (25–35 °C), pH (5.5–6.5), inoculum size (10–20% (v/v)), molasses concentration (25–35 (w/v)), mixing rate (110–150 rpm), and incubation period (48–72-h). Analysis of ethanol concentration was done by HPLC equipped with a UV detector.

Result
The optimal conditions of the parameters resulting in a maximum predicted ethanol yield were as follows: pH 5.5, an inoculum size of 20%, a molasses concentration of 25 °Bx, a temperature of 30 °C, an incubation period of 72-h, and a mixing rate of 160 revolutions per minute (rpm). Using the above optimum conditions, the model predicted a bioethanol yield of 79%, 92% of the theoretical yield, a bioethanol concentration of 49 g L−1, and a productivity of 0.68 g L−1 h−1. A batch fermentation experiment was carried out to validate the predicted values and resulted in a bioethanol yield of 86%, 95% of theoretical yield, a bioethanol concentration of 56 g L−1, and productivity of 0.78 g L−1 h−1. On the other hand, the surface plot analysis revealed that the synergistic effect of the molasses concentration and the mixing rate were vital to achieving the highest bioethanol yield. These values suggested that the RSM with CCD was an effective method in producing the highest possible output of bioethanol from molasses in actual operation.

Conclusion
The study confirmed the potential of using M. caribbica isolate MJTm3 for bioethanol production from sugarcane molasses under the abovementioned optimal fermentation conditions.
Self-Efficacy to Manage Chronic Disease (SEMCD) scale: translation and evaluation of measurement properties for a swedish version
Authors: Melin Jeanette , Fors Andreas , Jakobsson Sofie , Krabbe David , Björkman Ida 
Published: January 2023

Abstract
Background
Reinforcing self-efficacy in patients is important in person-centered care; therefore, reliable and valid measures of a person’s self-efficacy is of clinical relevance. A questionnaire suitable for self-efficacy and patient engagement that is not limited to a particular condition is the Self-efficacy to Manage Chronic Disease (SEMCD). This study aims to evaluate the measurement properties of a Swedish translation of the SEMCD with a Rasch analysis.

Methods
The translation and cultural adaptation of the SEMCD was performed according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations. Self-reported data was collected from two cohorts: patients with pituitary tumors (n = 86) and patients on sick leave due to common mental disorders (n = 209). Measurement properties were evaluated with a Rasch analysis in RUMM2030.

Results
The original six-item SEMCD did not fit to a unidimensional scale. Two items, item 5 and item 6, deviated both statistically and conceptually and were removed. A four-item solution, the SEMCD-4 with collapsed thresholds for mid-range response options, showed good targeting and unidimensionality, no item misfit, and a reliability of 0.83.

Conclusion
In a Swedish context with a mix of patients with pituitary tumors or common mental disorders, SEMCD-4 showed satisfactory measurement properties. Thus, SEMCD-4 could be used to identify patient self-efficacy in long-term illnesses. This knowledge about patient self-efficacy may be of importance to tailor person-centered support based on each patient´s resources, needs and goals.