bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Obex® in overweight and obese subjects: a randomised, double-blind, placebo-controlled clinical trial
Authors: Cabrera-Rode Eduardo , Cubas-Dueñas Ileana , Acosta Janet Rodríguez , Hernández Jeddú Cruz , González Ana Ibis Conesa , Calero Teresa M. González , Domínguez Yuri Arnold , Rodríguez José Hernández , Rodríguez Antonio D. Reyes , Álvarez Álvarez Aimee , Valdés Ragmila Echevarría , Espinosa Liudmila Jorge , Belent Onelia Torres , Benavides Zoila Bell , Estévez Elizabeth Senra , Rodríguez Yanet Abreu , del Valle Rodríguez Juana , Juliá Silvia Marín 
Published: February 2023

Abstract
Background
Obex® may be helpful in reducing body weight and fat. The current study was carried out to evaluate the efficacy and safety of Obex® in the treatment of overweight and obese subjects.

Methods
A double-blind, randomised, controlled phase III clinical trial was conducted involving 160 overweight and obese subjects (BMI ≥ 25.0 and < 40 kg/m2) aged 20 to 60 years, who received Obex® (n = 80) and placebo (n = 80) plus non-pharmacological treatment (physical activity and nutritional counseling). One sachet of Obex® or placebo were administered before the two main meals each day for 6 months. In addition to anthropometric measurements and blood pressure, fasting plasma and 2 h glucose levels during the oral glucose tolerance test, lipid profile, insulin, liver enzymes, creatinine, and uric acid (UA) were determined, insulin resistance (HOMA-IR) beta-cell function (HOMA-β) were assessed and insulin sensitivity (IS) was calculated with three indirect indexes.

Results
After 3 months of Obex®, 48.3% of the participants (28/58) achieved complete success in reducing both weight and waist circumference by greater than or equal to 5% from baseline, as opposed to 26.0% (13/50) of individuals receiving placebo (p = 0.022). Compared to baseline, at 6 months no differences were found between the groups concerning anthropometric and biochemical measurements, except for high-density lipoprotein cholesterol (HDL-c) levels, which were higher in subjects receiving Obex® compared to those receiving placebo (p = 0.030). After 6 months of treatment, both groups showed reduced cholesterol and triglyceride levels (p < 0.012) compared to baseline value. However, only those intake Obex® showed reduced insulin concentrations and HOMA-IR, improved IS (p < 0.05), and decreased creatinine and UA levels (p < 0.005).

Conclusions
The consumption of Obex® together with lifestyle changes increased HDL-c, contributed to a rapid reduction of weight and waist circumference, as well as improved insulin homeostasis, which did not occur in the placebo group, and appears to be safe as an adjunct at conventional obesity treatment.

Trial registration
Clinical trial protocol was registered in the Cuban public registry of clinical trials under code RPCEC00000267 on 17/04/2018 and also registered in the international registry of clinical trials, ClinicalTrials.gov, under code: NCT03541005 on 30/05/2018.
Referral patterns for retinoblastoma patients in Ethiopia
Authors: Sherief Sadik Taju , Wu Fran , O’Banion Jacquelyn , Teshome Tiliksew , Dimaras Helen 
Published: February 2023

Abstract
Background
Increased lag time between the onset of symptoms and treatment of retinoblastoma (RB) is one of the factors contributing to delay in diagnosis. The aim of this study was to understand the referral patterns and lag times for RB patients who were treated at Menelik II Hospital in Addis Ababa, Ethiopia.

Method
A single-center, cross- sectional study was conducted in January 2018. All new patients with a confirmed RB diagnosis who had presented to Menelik II Hospital from May 2015 to May 2017 were eligible. A questionnaire developed by the research team was administered to the patient’s caregiver by phone.

Results
Thirty-eight patients were included in the study and completed the phone survey. Twenty-nine patients (76.3%) delayed seeing a health care provider for ≥ 3 months from the onset of symptoms, with the most common reason being the belief that it was not a problem (96.5%), followed by 73% saying it was too expensive. The majority of patients (37/38, 97.4%) visited at least 1 additional health care facility prior to reaching a RB treatment facility. The mean overall lag time from noticing the first symptom to treatment was 14.31 (range 0.25–62.25) months.

Conclusion
Lack of knowledge and cost are major barriers to patients first seeking care for RB symptoms. Cost and travel distance are major barriers to seeing referred providers and receiving definitive treatment. Delays in care may be alleviated by public education, early screening, and public assistance programs.
Associations of reproductive factors with incidence of myocardial infarction and ischemic stroke in postmenopausal women: a cohort study
Authors: Jeong Su-Min , Yoo Jung Eun , Jeon Keun Hye , Han Kyungdo , Lee Heesun , Lee Dong-Yun , Shin Dong Wook 
Published: February 2023

Abstract
Background

To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS).

Methods
We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13–14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40–45, 46–50, 51–54 [reference], and ≥ 55 years), and reproductive span (< 30, 30–33, 34–36, 37–40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors.

Results
During a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12–40%, and 12–32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7–9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS.

Conclusions
This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women.
Comprehensive analysis of PHGDH for predicting prognosis and immunotherapy response in patients with endometrial carcinoma
Authors: Zhang He , Kong Weimin , Zhao Xiaoling , Xie Yunkai , Luo Dan , Chen Shuning 
Published: February 2023

Abstract
Background
PHGDH (Phosphoglycerate Dehydrogenase) is the first branch enzyme in the serine biosynthetic pathway and plays a vital role in several cancers. However, little is known about the clinical significance of PHGDH in endometrial cancer.

Methods
Clinicopathological data of endometrial cancer were downloaded from the Cancer Genome Atlas database (TCGA). First, the expression of PHGDH in pan-cancer was investigated, as well as the expression and prognostic value of PHGDH in endometrial cancer. The effect of PHGDH expression on the prognosis of endometrial cancer was analyzed by Kaplan-Meier plotter and Cox regression. The relationship between PHGDH expression and clinical characteristics of endometrial cancer was investigated by logistic regression. Receiver operating characteristic (ROC) curves and nomograms were developed. Possible cellular mechanisms were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the Gene Ontology (GO), and gene set enrichment analysis (GSEA). Finally, TIMER and CIBERSORT were used to analyze the relationship between PHGDH expression and immune infiltration. CellMiner™ was used to analyze the drug sensitivity of PHGDH.

Results
The results showed that PHGDH expression was significantly higher in endometrial cancer tissues than in normal tissues at mRNA and protein levels. Kaplan-Meier survival curves showed that patients in the high expression group had shorter overall survival (OS) and disease free survival (DFS) than patients in the low PHGDH expression group. Multifactorial COX regression analysis further supported that high PHGDH expression was an independent risk factor associated with prognosis in patients with endometrial cancer. The results showed estrogen response, mTOR, K-RAS, and epithelial mesenchymal transition (EMT) were differentially elevated in the high-expression group of the PHGDH group. CIBERSORT analysis showed that PHGDH expression is related to the infiltration of multiple immune cells. When PHGDH is highly expressed, the number of CD8+T cells decreases.

Conclusion
PHGDH plays a vital role in the development of endometrial cancer, which is related to tumor immune infiltration, and can be used as an independent diagnostic and prognostic marker for endometrial cancer.
Malaria in pregnancy (MiP) studies assessing the clinical performance of highly sensitive rapid diagnostic tests (HS-RDT) for Plasmodium falciparum detection
Authors: Ding Xavier C. , Incardona Sandra , Serra-Casas Elisa , Charnaud Sarah C. , Slater Hannah C. , Domingo Gonzalo J. , Adams Emily R. , ter Kuile Feiko O. , Samuels Aaron M. , Kariuki Simon , Dittrich Sabine 
Published: February 2023

Abstract
Background
Rapid diagnostic tests (RDTs) are effective tools to diagnose and inform the treatment of malaria in adults and children. The recent development of a highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum has prompted questions over whether it could improve the diagnosis of malaria in pregnancy and pregnancy outcomes in malaria endemic areas.

Methods
This landscape review collates studies addressing the clinical performance of the HS-RDT. Thirteen studies were identified comparing the HS-RDT and conventional RDT (co-RDT) to molecular methods to detect malaria in pregnancy. Using data from five completed studies, the association of epidemiological and pregnancy-related factors on the sensitivity of HS-RDT, and comparisons with co-RDT were investigated. The studies were conducted in 4 countries over a range of transmission intensities in largely asymptomatic women.

Results
Sensitivity of both RDTs varied widely (HS-RDT range 19.6 to 85.7%, co-RDT range 22.8 to 82.8% compared to molecular testing) yet HS-RDT detected individuals with similar parasite densities across all the studies including different geographies and transmission areas [geometric mean parasitaemia around 100 parasites per µL (p/µL)]. HS-RDTs were capable of detecting low-density parasitaemias and in one study detected around 30% of infections with parasite densities of 0–2 p/µL compared to the co-RDT in the same study which detected around 15%.

Conclusion
The HS-RDT has a slightly higher analytical sensitivity to detect malaria infections in pregnancy than co-RDT but this mostly translates to only fractional and not statistically significant improvement in clinical performance by gravidity, trimester, geography or transmission intensity. The analysis presented here highlights the need for larger and more studies to evaluate incremental improvements in RDTs. The HS-RDT could be used in any situation where co-RDT are currently used for P. falciparum diagnosis, if storage conditions can be adhered to.
Harm reduction behaviors are associated with carrying naloxone among patients on methadone treatment
Authors: Kozak Zofia , Ciccarone Daniel , Thrul Johannes , Cole Thomas O. , Pappas Alexander L. , Greenblatt Aaron D. , Welsh Christopher , Yoon Mark , Gann Donald , Artigiani E. Erin , Wish Eric D. , Belcher Annabelle M. 
Published: February 2023

Abstract
Background
Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The “Cascade of Care” (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors.

Methods
Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors.

Results
Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02–8.52), college education (aOR = 8.11, 95% CI 1.76–37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00–2.11).

Conclusion
We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.
Dosimetric and clinical analysis of pseudo-progression versus recurrence after hypo-fractionated radiotherapy for brain metastases
Authors: Yang Siran , Ma Yuchao , Xu Yingjie , Liu Qingfeng , Zhang Ye , Huang Xiaodong , Chen Xuesong , Wang Kai , Zhao Ruizhi , Xiao Jianping , Zhang Hongmei 
Published: February 2023

Abstract
Background
The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors.

Methods
The study included 123 patients with enlarged brain metastases after hypo-fractionated radiotherapy in our center from March 2009 to October 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. Independent risk factors with P < 0.05 and associated with recurrence were used to establish a nomogram prediction model and validated by Bootstrap repeated sampling, ﻿which was validated in an internal cohort (n = 23) from October 2019 to December 2021.

Results
The median follow-up time was 68.4 months (range, 8.9–146.2 months). A total of 76 (61.8%) patients were evaluated as pseudo-progression, 47 patients (38.2%) were evaluated as tumor recurrence. The median time to pseudo-progression and tumor recurrence were 18.3 months (quartile range, 9.4–27.8 months) and 12.9 months (quartile range, 8.7–19.6 months) respectively. Variables associated with tumor recurrence included: gross tumor volume ≥ 6 cc, biological effective dose < 60 Gy, target coverage < 96% and no targeted therapy. The area under curve values were 0.730 and 0.967 in the training and validation cohorts, respectively. Thirty-one patients received salvage therapy in the tumor recurrence group. The survival time in pseudo-progression and tumor recurrence groups were 66.3 months (95% CI 56.8–75.9 months) and 39.6 months (95% CI 29.2–50.0 months, respectively; P = 0.001).

Conclusions
Clinical and dosimetry features of hypo-fractionated radiation therapy based on enhanced brain magnetic resonance can help distinguish pseudo-progression from tumor recurrence after hypo-fractionated radiotherapy for brain metastases. Gross tumor volume, biological effective dose, target coverage, and having received targeted therapy or not were factors associated with the occurrence of tumor recurrence, and the individual risk could be estimated by the nomogram effectively.
Effect of resistance vs. aerobic exercise in pre-diabetes: an RCT
Authors: Luo Xijuan , Wang Zhengzhen , Li Bowen , Zhang Xianbo , Li Xin 
Published: February 2023

Abstract
Background
This study aimed to assess the different impacts of aerobic and resistance exercise intervention on pre-diabetes and its possible influencing factor (obesity) to identify which exercise intervention mode was better for pre-diabetes to control their blood glucose levels.

Methods
Single-blind randomized controlled trial. Participants were recruited from Southwest Hospital between February 2016 and May 2017 and randomly divided into three groups using stratified randomization: aerobic exercise (A), resistance exercise (R), and control (C). The effects of each group were analyzed, and the relationship with obesity was investigated following a 12-week intervention.

Results
Eighty participants were enrolled (9 were lost, and 1 was excluded). Finally, 26 participants were included in group A, 23 in group R, and 21 in group C. In groups A and R, FPG, OGTT 2-h PG, and HOMA2-IR decreased by 6.17% (P = 0.001) and 4.81% (P = 0.019), 20.39% (P < 0.001) and 16.50% (P < 0.001), and 8.34% (P = 0.026) and 18.31% (P = 0.001, superior to that in group A), respectively (all P < 0.001 compared with group C, with no significant differences between groups A and R). The ratio of reversal to euglycemia was 69.2% (P = 0.003 compared with group C) in group A and 43.5% (P = 0.213 compared with group C) in group R. The decreased ratio of GSP in group R was greater (65.2%, P = 0.008 compared with group C) compared with group A (38.5%, P = 0.355 compared with group C). Decreases in the parameters BMI (3.1 ± 3.2% P < 0.001, moderately positive correlation with the decreased FPG level, r = 0.498, P = 0.010, two-tailed) and waist circumference (3.1 ± 2.7% P < 0.001) were noted in group A, but no significant correlations were noted between other indicators in group R.

Conclusions
Both resistance and aerobic exercise can control and reverse IGR. Compared with aerobic exercise, resistance exercise may be superior in terms of GSP and IR improvement. Aerobic exercise decreases blood glucose levels through weight loss. However, the effect of resistance exercise might not be mediated via weight loss and obesity control.

Trial registration
Chinese Clinical Trial Registry ChiCTR2000038304. Registered on September 17, 2020.
Developing a genetic engineering method for Acetobacterium wieringae to expand one-carbon valorization pathways
Authors: Moreira João P. C. , Heap John T. , Alves Joana I. , Domingues Lucília 
Published: February 2023

Abstract
Background
Developing new bioprocesses to produce chemicals and fuels with reduced production costs will greatly facilitate the replacement of fossil-based raw materials. In most fermentation bioprocesses, the feedstock usually represents the highest cost, which becomes the target for cost reduction. Additionally, the biorefinery concept advocates revenue growth from the production of several compounds using the same feedstock. Taken together, the production of bio commodities from low-cost gas streams containing CO, CO2, and H2, obtained from the gasification of any carbon-containing waste streams or off-gases from heavy industry (steel mills, processing plants, or refineries), embodies an opportunity for affordable and renewable chemical production. To achieve this, by studying non-model autotrophic acetogens, current limitations concerning low growth rates, toxicity by gas streams, and low productivity may be overcome. The Acetobacterium wieringae strain JM is a novel autotrophic acetogen that is capable of producing acetate and ethanol. It exhibits faster growth rates on various gaseous compounds, including carbon monoxide, compared to other Acetobacterium species, making it potentially useful for industrial applications. The species A. wieringae has not been genetically modified, therefore developing a genetic engineering method is important for expanding its product portfolio from gas fermentation and overall improving the characteristics of this acetogen for industrial demands.

Results
This work reports the development and optimization of an electrotransformation protocol for A. wieringae strain JM, which can also be used in A. wieringae DSM 1911, and A. woodii DSM 1030. We also show the functionality of the thiamphenicol resistance marker, catP, and the functionality of the origins of replication pBP1, pCB102, pCD6, and pIM13 in all tested Acetobacterium strains, with transformation efficiencies of up to 2.0 × 103 CFU/μgDNA. Key factors affecting electrotransformation efficiency include OD600 of cell harvesting, pH of resuspension buffer, the field strength of the electric pulse, and plasmid amount. Using this method, the acetone production operon from Clostridium acetobutylicum was efficiently introduced in all tested Acetobacterium spp., leading to non-native biochemical acetone production via plasmid-based expression.

Conclusions
A. wieringae can be electrotransformed at high efficiency using different plasmids with different replication origins. The electrotransformation procedure and tools reported here unlock the genetic and metabolic manipulation of the biotechnologically relevant A.wieringae strains. For the first time, non-native acetone production is shown in A. wieringae.
Bilateral central retinal vein occlusion as an initial presentation of Waldenström macroglobulinemia: a case report
Authors: Shrestha Suraj , Poddar Elisha , Bashyal Bibhav , Adhikari Aayush , Pathak Prabin , Acharya Suman , Sapkota Surendra , Bhattarai Anjan , Pant Samriddha Raj , Shrestha Anjan 
Published: February 2023

Abstract
Background
Waldenström macroglobulinemia is a rare hematological malignancy and is the most common diagnosis in patients with hyperviscosity syndrome. Bilateral central retinal vein occlusion as an initial presentation of hyperviscosity syndrome in Waldenström macroglobulinemia is rare.

Case presentation
A 42-year-old Nepalese male presented with sudden-onset bilateral painless blurring of vision. Fundus examination revealed bilateral, diffusely dilated, tortuous retinal veins and intraretinal deep blot hemorrhages in all four quadrants of the retina in both eyes; features of bilateral central retinal vein occlusion. Serum electrophoresis showed hypoalbuminemia with an immunoglobulin M kappa monoclonal spike. Bone marrow picture and immunohistochemistry analysis were suggestive of lymphoplasmacytic lymphoma. The patient received systemic therapy for Waldenström macroglobulinemia, along with intravitreal bevacizumab.

Conclusion
Adequate hydration, plasmapheresis, and a combination of bortezomib, dexamethasone, and rituximab regimen as a systemic therapy may represent an ideal choice for patients with hyperviscosity in Waldenström macroglobulinemia.