bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing enzyme properties to enhance dihydroxyacetone production via methylglyoxal biosensor development
Authors: Zhang Kaibo , Li Mengying , Wang Jinsheng , Huang Guozhong , Ma Kang , Peng Jiani , Lin Haoyue , Zhang Chunjie , Wang Honglei , Zhan Tao , Sun Zhe , Zhang Xueli 
Published: May 2024

Abstract
Background
Dihydroxyacetone (DHA) stands as a crucial chemical material extensively utilized in the cosmetics industry. DHA production through the dephosphorylation of dihydroxyacetone phosphate, an intermediate product of the glycolysis pathway in Escherichia coli, presents a prospective alternative for industrial production. However, insights into the pivotal enzyme, dihydroxyacetone phosphate dephosphorylase (HdpA), remain limited for informed engineering. Consequently, the development of an efficient tool for high-throughput screening of HdpA hypermutants becomes imperative.

Results
This study introduces a methylglyoxal biosensor, based on the formaldehyde-responding regulator FrmR, for the selection of HdpA. Initial modifications involved the insertion of the FrmR binding site upstream of the −35 region and into the spacer region between the −10 and −35 regions of the constitutive promoter J23110. Although the hybrid promoter retained constitutive expression, expression of FrmR led to complete repression. The addition of 350 μM methylglyoxal promptly alleviated FrmR inhibition, enhancing promoter activity by more than 40-fold. The methylglyoxal biosensor system exhibited a gradual increase in fluorescence intensity with methylglyoxal concentrations ranging from 10 to 500 μM. Notably, the biosensor system responded to methylglyoxal spontaneously converted from added DHA, facilitating the separation of DHA producing and non-producing strains through flow cytometry sorting. Subsequently, the methylglyoxal biosensor was successfully applied to screen a library of HdpA mutants, identifying two strains harboring specific mutants 267G > T and D110G/G151C that showed improved DHA production by 68% and 114%, respectively. Expressing of these two HdpA mutants directly in a DHA-producing strain also increased DHA production from 1.45 to 1.92 and 2.29 g/L, respectively, demonstrating the enhanced enzyme properties of the HdpA mutants.

Conclusions
The methylglyoxal biosensor offers a novel strategy for constructing genetically encoded biosensors and serves as a robust platform for indirectly determining DHA levels by responding to methylglyoxal. This property enables efficiently screening of HdpA hypermutants to enhance DHA production.
Insecticide susceptibility status of Anopheles albimanus populations in historical malaria foci in Quintana Roo, Mexico
Authors: Escobar Denis , González-Olvera Gabriela , Gómez-Rivera Ángel S. , Navarrete-Carballo Juan , Mis-Ávila Pedro , Baack-Valle Raquel , Escalante Guillermo , Reyes-Cabrera Gerardo , Correa-Morales Fabian , Che-Mendoza Azael , Vazquez-Prokopec Gonzalo , Lenhart Audrey , Manrique-Saide Pablo 
Published: May 2024

Abstract
Background
Mexico has experienced a significant reduction in malaria cases over the past two decades. Certification of localities as malaria-free areas (MFAs) has been proposed as a steppingstone before elimination is achieved throughout the country. The Mexican state of Quintana Roo is a candidate for MFA certification. Monitoring the status of insecticide susceptibility of major vectors is crucial for MFA certification. This study describes the susceptibility status of Anopheles albimanus, main malaria vector, from historically important malaria foci in Quintana Roo, using both phenotypic and genotypic approaches.

Methods
Adult mosquito collections were carried out at three localities: Palmar (Municipality of Othon P. Blanco), Buenavista (Bacalar) and Puerto Morelos (Puerto Morelos). Outdoor human-landing catches were performed by pairs of trained staff from 18:00 to 22:00 during 3-night periods at each locality during the rainy season of 2022. Wild-caught female mosquitoes were exposed to diagnostic doses of deltamethrin, permethrin, malathion, pirimiphos-methyl or bendiocarb using CDC bottle bioassays. Mortality was registered at the diagnostic time and recovery was assessed 24 h after exposure. Molecular analyses targeting the Voltage-Gated Sodium Channel (vgsc) gene and acetylcholinesterase (ace-1) gene were used to screen for target site polymorphisms. An SNP analysis was carried out to identify mutations at position 995 in the vgsc gene and at position 280 in the ace-1 gene.

Results
A total of 2828 anophelines were collected. The main species identified were Anopheles albimanus (82%) and Anopheles vestitipennis (16%). Mortalities in the CDC bottle bioassay ranged from 99% to 100% for all the insecticides and mosquito species. Sequence analysis was performed on 35 An. albimanus across the three localities; of those, 25 were analysed for vgsc and 10 for ace-1 mutations. All individuals showed wild type alleles.

Conclusion
The results demonstrated that An. albimanus populations from historical malaria foci in Quintana Roo are susceptible to the main insecticides used by the Ministry of Health.
Non-communicable diseases and its risk factors among the transgender population in Kerala: a cross-sectional study
Authors: Fernandez Bhavya , Gaitonde Rakhal 
Published: May 2024

Abstract
Background
Non-communicable diseases (NCDs) are high on the priority list of the Kerala government, and exploring the extent to which transgender and gender diverse (TGD) community members benefit from the services of national programmes for NCDs can provide valuable insights on improving the inclusivity of the health system as it moves towards Universal Health Coverage. This study was conducted to explore the prevalence of NCD risk factors as well as facilitators and barriers to NCD management among the TGD population in Kerala.

Methods
A multiple methods study, including a cross-sectional survey of 120 self-identifying TGD people that included an adaptation of the WHO STEPS questionnaire, as well as in-depth interviews with thirteen individuals, was conducted in three districts of Kerala to explore the barriers and facilitators to NCD prevention and management.

Results
The results are presented using the key dimensions emerging out of the Diederichsen framework. A range of discrimination faced by TGD people in Kerala traps them in situations of low educational outcomes with consequent disadvantages in the job market when they search for livelihoods. This results in a large proportion of our sample living away from families (69 percent), and finding themselves in precarious jobs including sex work (only 33 percent had a regular job), with all these aforementioned factors converging to marginalise their social position. This social position leads to differential risk exposures such as increased exposure to modifiable risk factors like alcohol (40 percent were current alcohol users) and tobacco use (40.8 percent currently used tobacco) and ultimately metabolic risk factors too (30 and 18 percent were hypertensive and diabetic respectively). Due to their differential vulnerabilities such as the discrimination that TGD people are subjected to (41.7 percent had faced discrimination at a healthcare centre in the past one year), those with higher exposure to risk factors often find it hard to bring about behavioural modifications and are often not able to access the services they require.

Conclusions
The disadvantaged social position of TGD people and associated structural issues result in exacerbated biological risks, including those for NCDs. Ignoring these social determinants while designing health programmes is likely to lead to sub-optimal outcomes.
Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Gong Yong , Bai Xueyan , Zhang Donglei , Yang Xingsheng , Qin Zheng , Yang Yu , Zhou Yilun , Meng Jie , Liu Xin 
Published: May 2024

Abstract
Aims
About 20–40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM.

Methods
A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively.

Results
A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg’s and Egger’s tests.

Conclusions
Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM.

International Prospective Register for Systematic Review (PROSPERO) number
CRD.42020144642.
Targeting PCSK9 as a key player in lipid metabolism: exploiting the therapeutic and biosensing potential of aptamers
Authors: Mahjoubin-Tehran Maryam , Rezaei Samaneh , Santos Raul D. , Jamialahmadi Tannaz , Almahmeed Wael , Sahebkar Amirhossein 
Published: May 2024

AbstractThe degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2’-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.
Exosome-sheathed porous silica nanoparticle-mediated co-delivery of 3,3′-diindolylmethane and doxorubicin attenuates cancer stem cell-driven EMT in triple negative breast cancer
Authors: Sarkar Rupali , Biswas Souradeep , Ghosh Rituparna , Samanta Priya , Pakhira Shampa , Mondal Mrinmoyee , Dutta Gupta Yashaswi , Bhandary Suman , Saha Prosenjit , Bhowmik Arijit , Hajra Subhadip 
Published: May 2024

Abstract
Background
Therapeutic management of locally advanced and metastatic triple negative breast cancer (TNBC) is often limited due to resistance to conventional chemotherapy. Metastasis is responsible for more than 90% of breast cancer-associated mortality; therefore, the clinical need to prevent or target metastasis is immense. The epithelial to mesenchymal transition (EMT) of cancer stem cells (CSCs) is a crucial determinant in metastasis. Doxorubicin (DOX) is the frequently used chemotherapeutic drug against TNBC that may increase the risk of metastasis in patients. After cancer treatment, CSCs with the EMT characteristic persist, which contributes to advanced malignancy and cancer recurrence. The latest developments in nanotechnology for medicinal applications have raised the possibility of using nanomedicines to target these CSCs. Hence, we present a novel approach of combinatorial treatment of DOX with dietary indole 3,3′-diindolylmethane (DIM) which is an intriguing field of research that may target CSC mediated EMT induction in TNBC. For efficient delivery of both the compounds to the tumor niche, advance method of drug delivery based on exosomes sheathed with mesoporous silica nanoparticles may provide an attractive strategy.

Results
DOX, according to our findings, was able to induce EMT in CSCs, making the breast cancer cells more aggressive and metastatic. In CSCs produced from spheres of MDAMB-231 and 4T1, overexpression of N-cadherin, Snail, Slug, and Vimentin as well as downregulation of E-cadherin by DOX treatment not only demonstrated EMT induction but also underscored the pressing need for a novel chemotherapeutic combination to counteract this detrimental effect of DOX. To reach this goal, DIM was combined with DOX and delivered to the CSCs concomitantly by loading them in mesoporous silica nanoparticles encapsulated in exosomes (e-DDMSNP). These exosomes improved the specificity, stability and better homing ability of DIM and DOX in the in vitro and in vivo CSC niche. Furthermore, after treating the CSC-enriched TNBC cell population with e-DDMSNP, a notable decrease in DOX mediated EMT induction was observed.

Conclusion
Our research seeks to propose a new notion for treating TNBC by introducing this unique exosomal nano-preparation against CSC induced EMT.

Graphical Abstract
Change in substance use among patients in opioid maintenance treatment: baseline to 1-year follow-up
Authors: Bjørnestad Endre Dahlen , Vederhus John-Kåre , Clausen Thomas 
Published: May 2024

Abstract
Background
Individuals with opioid use disorder (OUD) often have concurrent use of non-opioid substances. When patients enter opioid maintenance treatment (OMT), less is known about outcomes regarding the use of other types of drugs. Here we aimed to investigate changes in substance use among patients entering outpatient OMT, from treatment initiation to 1-year follow-up.

Methods
We used data from the prospective Norwegian Cohort of Patient in OMT and Other Drug Treatment Study (NorComt). Among 283 patients who entered OMT at participating facilities across Norway, 179 were assessed at follow-up. Of these patients, 131 were in a non-controlled environment, and were included in the present analysis. The main outcome was change in substance use. Logistic regression analysis was applied to identify factors associated with abstinence from all substances (other than agonist medication) at follow-up.

Results
Along with opioid use, most patients reported polysubstance use prior to entering treatment. No significant differences were found in baseline characteristics between the included and non-included groups when examining attrition. At the 1-year follow-up, reduced substance use was reported. While in treatment, around two-thirds of patients continued using other drugs to varying degrees. At follow-up, about one-third of patients reported abstinence from all drugs, apart from the agonist medication. Factors related to abstinence included a goal of abstinence at baseline (OR = 5.26; 95% CI 1.14–19.55; p = 0.013) and increasing age (OR = 1.05; 95% CI 1.00–1.09; p = 0.034).

Conclusions
The majority of patients entering OMT used other substances in addition to opioids. About one-third of patients reported abstinence at the 1-year follow up. Although the majority of patients continued co-use of other drugs while in treatment, for most substances, less than 10% reported daily use at follow-up, with the exception of cannabis which was used daily/almost daily by about 2 in 10. Higher age and treatment goal at the start of OMT were important factors related to reducing concomitant substance use during treatment. These findings suggest that many patients entering OMT are in need of treatment and support related to the use of other substances, to further improve prognosis.

Clinical trial registration
Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).
Quality check: concordance between two monitoring systems for postoperative organ/space-surgical site infections in rectal cancer surgery. Linkage of data from the Catalan Cancer Plan and the VINCat infection surveillance programme
Authors: Matallana Carlota , Pera Miguel , Espin-Basany Eloy , Biondo Sebastiano , Badia Josep M , Limon Enric , Pujol Miquel , de Lacy Borja , Aliste Luisa , Borràs Josep M , Manchon-Walsh Paula 
Published: May 2024

Abstract
Background
The Catalan Cancer Plan (CCP) undertakes periodic audits of cancer treatment outcomes, including organ/space surgical site infections (O/S-SSI) rates, while the Catalan Healthcare-associated Infections Surveillance Programme (VINCat) carries out standardized prospective surveillance of surgical site infections (SSI) in colorectal surgery. This cohort study aimed to assess the concordance between these two monitoring systems for O/S-SSI following primary rectal cancer surgery.

Methods
The study compared O/S-SSI incidence data from CCP clinical audits versus the VINCat Programme in patients undergoing surgery for primary rectal cancer, in 2011-12 and 2015-16, in publicly funded centres in Spain. The main outcome variable was the incidence of O/S-SSI in the first 30 days after surgery. Concordance between the two registers was analysed using Cohen’s kappa. Discordant cases were reviewed by an expert, and the main reasons for discrepancies evaluated.

Results
Pooling data from both databases generated a sample of 2867 patients. Of these, O/S-SSI was detected in 414 patients—235 were common to both registry systems, with satisfactory concordance (κ = 0.69, 95% confidence interval 0.65–0.73). The rate of discordance from the CCP (positive cases in VINCat and negative in CCP) was 2.7%, and from VINCat (positive in CCP and negative in VINCat) was 3.6%. External review confirmed O/S-SSI in 66.2% of the cases in the CCP registry and 52.9% in VINCat.

Conclusions
This type of synergy shows the potential of pooling data from two different information sources with a satisfactory level of agreement as a means to improving O/S-SSI detection. ClinicalTrials.gov Identifier: NCT06104579. Registered 30 November 2023.
Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth
Authors: Guo Huaizhu , Chen Yuzhu , Dong Wenxin , Lu Siqi , Du Yanlin , Duan Liping 
Published: May 2024

Abstract
Background
Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals.

Methods
To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing.

Results
Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO.

Conclusions
This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus’s abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT’s complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.
Evaluation of the rapid Idylla IDH1-2 mutation assay in FFPE glioma samples
Authors: Solomon James P. , Munoz-Zuluaga Carlos , Slocum Cheyanne , Dillard Alicia , Cong Lin , Wang Jiajing , Lindeman Neal , Kluk Michael , Liechty Benjamin , Pisapia David , Rennert Hanna , Velu Priya D. 
Published: May 2024

AbstractIDH1 and IDH2 mutational status is a critical biomarker with diagnostic, prognostic, and treatment implications in glioma. Although IDH1 p.R132H-specific immunohistochemistry is available, it is unable to identify other mutations in IDH1/2. Next-generation sequencing can accurately determine IDH1/2 mutational status but suffers from long turnaround time when urgent treatment planning and initiation is medically necessary. The Idylla assay can detect IDH1/2 mutational status from unstained formalin-fixed paraffin-embedded (FFPE) slides in as little as a few hours. In a clinical validation, we demonstrate clinical accuracy of 97% compared to next-generation sequencing. Sensitivity studies demonstrated a limit of detection of 2.5-5% variant allele frequency, even at DNA inputs below the manufacturer’s recommended threshold. Overall, the assay is an effective and accurate method for rapid determination of IDH1/2 mutational status.