bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of protein production in Aspergillus niger by engineering the antioxidant defense metabolism
Authors: Chen Xin , Pan Baoxiang , Yu Leyi , Wang Bin , Pan Li 
Published: July 2024

Abstract
Background
Research on protein production holds significant importance in the advancement of food technology, agriculture, pharmaceuticals, and bioenergy. Aspergillus niger stands out as an ideal microbial cell factory for the production of food-grade proteins, owing to its robust protein secretion capacity and excellent safety profile. However, the extensive oxidative folding of proteins within the endoplasmic reticulum (ER) triggers ER stress, consequently leading to protein misfolding reactions. This stressful phenomenon results in the accelerated generation of reactive oxygen species (ROS), thereby inducing oxidative stress. The accumulation of ROS can adversely affect intracellular DNA, proteins, and lipids.

Result
In this study, we enhanced the detoxification of ROS in A. niger (SH-1) by integrating multiple modules, including the NADPH regeneration engineering module, the glutaredoxin system, the GSH synthesis engineering module, and the transcription factor module. We assessed the intracellular ROS levels, growth under stress conditions, protein production levels, and intracellular GSH content. Our findings revealed that the overexpression of Glr1 in the glutaredoxin system exhibited significant efficacy across various parameters. Specifically, it reduced the intracellular ROS levels in A. niger by 50%, boosted glucoamylase enzyme activity by 243%, and increased total protein secretion by 88%.

Conclusion
The results indicate that moderate modulation of intracellular redox conditions can enhance overall protein output. In conclusion, we present a strategy for augmenting protein production in A. niger and propose a potential approach for optimizing microbial protein production system.
Mesenchymal stem cells ameliorate inflammation and pyroptosis in diabetic cardiomyopathy via the miRNA-223-3p/NLRP3 pathway
Authors: Yang Qu , Chen Qi , Li Sihui , Luo Jun 
Published: July 2024

Abstract
Background
Diabetic cardiomyopathy (DCM) stands as the primary cause of heart failure and mortality among patients with diabetes. Nevertheless, conventional treatment approaches are limited in their ability to effectively prevent myocardial tissue damage itself. Mesenchymal stem cell (MSC) therapy exhibits immense potential for treating DCM; however, the precise mechanisms involved in regulating inflammatory responses and pyroptosis processes, an emerging form of cellular death, within myocardial cells remain elusive. Hence, it is imperative to further elucidate the precise underlying mechanisms to facilitate the clinical implementation of MSC therapy.

Methods
In vivo, we established a DCM mouse model by administering streptozotocin and fed the mice a high-glucose and high-fat diet, followed by MSC therapy. Cardiac function and myocardial injury were evaluated through echocardiography and histological analysis. Furthermore, the levels of inflammation and pyroptosis were assessed using ELISA, Western blotting, and qRT-PCR. In vitro experiments involved inducing H9C2 myocardial cell damage with high glucose treatment, followed by coculture with MSCs to investigate their role in modulating inflammation and pyroptosis mechanisms.

Results
MSCs can maintain cardiac function and alleviate myocardial injury in mice with DCM. Moreover, they effectively suppress the activation of NLRP3 and reduce the release of inflammatory factors (such as IL-1β and ROS), thereby further downregulating the expression of pyroptosis-related proteins including NLRP3, Caspase-1, and GSDMD. Additionally, we experimentally validated that MSCs exert their therapeutic effects by promoting the expression of miR-223-3p in cardiac myocytes; however, this effect can be reversed by an miR-223-3p inhibitor.

Conclusion
MSCs effectively mitigate the release of inflammatory factors and cell lysis caused by pyroptosis through the regulation of the miR-223-3p/NLRP3 pathway, thereby safeguarding cardiomyocytes against damage in DCM. This mechanism establishes a novel theoretical foundation for the clinical treatment of cardiac conditions utilizing MSCs.
Hypoimmunogenic human iPSCs expressing HLA-G, PD-L1, and PD-L2 evade innate and adaptive immunity
Authors: Tsuneyoshi Norihiro , Hosoya Tomonori , Takeno Yuriko , Saitoh Kodai , Murai Hidetaka , Amimoto Naoki , Tatsumi Rie , Watanabe Sono , Hasegawa Yudai , Kikkawa Eri , Goto Kumiko , Nishigaki Fusako , Tamura Kouichi , Kimura Hironobu 
Published: July 2024

Abstract
Background
The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch.

Methods
First, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed.

Results
We found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45+ hematopoietic progenitor cells (HPCs), functional endothelial cells, and hepatocytes. The HyPSCs-derived HPCs exhibited the ability to evade innate and adaptive immunity. Further, we demonstrated that RapaCasp9 could be used as a safety switch in vitro and in vivo.

Conclusion
The HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.
Rising socioeconomic disparities in childhood overweight and obesity in Belgium
Authors: Drieskens Sabine , Charafeddine Rana , Vandevijvere Stefanie , De Pauw Robby , Demarest Stefaan 
Published: July 2024

Abstract
Background
Childhood overweight, especially obesity, significantly impacts children’s health and poses an increased risk of adult-onset diseases. This study aims to analyse the evolution of childhood overweight and obesity in Belgium from 1997 to 2018 and assess its variation across parental socioeconomic status (SES).

Methods
The Health Interview Survey, a cross-sectional survey representative of the Belgian population, has been conducted since 1997, with the latest survey conducted in 2018. This study focuses on children aged 2–17 years. Body Mass Index (BMI, kg/m²) was derived from self-reported data, supplemented with proxy reports for children under 15 years old. Overweight and obesity were classified using age/sex-specific cut-off points. Highest parental educational level served as the indicator of SES. In addition to reporting the overall prevalence and the 95% confidence interval (95%CI) of childhood overweight and obesity by year, this study examines the absolute difference in prevalence between SES groups (low minus high) and calculates the Odds Ratio (OR, adjusted for age and sex) to evaluate the relative difference.

Results
The overall prevalence of childhood overweight rose from 13.6% (95%CI = 11.2-16.1%) in 1997 to 18.9% (95%CI = 16.3-21.5%) in 2018; while it remained stable for obesity, fluctuating between 5.4% and 6.3% over the same period. This increase was more pronounced among children with low SES compared to those with high SES. Consequently, the absolute difference between children with low and high SES increased over time from 8.0% points (pp) in 1997 to 14.9 pp in 2018 for overweight, and from 3.1 pp to 6.8 pp for obesity. In terms of relative inequalities, overall, children with low SES exhibited significantly higher odds of overweight and of obesity than those with high SES (OR varying between 2 à 3 for overweight and between 2 and 4 for obesity).

Conclusions
The escalating disparities over time highlight SES as a significant risk factor for childhood overweight and obesity. Addressing these inequalities requires interventions such as providing healthy meals and increasing sports opportunities at school. Additionally, it is recommended to regulate fast food outlets near schools and limit unhealthy food marketing, particularly because children with low SES are more exposed to such influences.
A stony track towards innovation in remote highland regions: agricultural intensification in the apricot sector of Northern Pakistan
Authors: Köster Mareike , Alam Iftikhar , Rana Jai , Wiehle Martin , Buerkert Andreas 
Published: July 2024

Abstract
Background
Traditional farming practices of remote highland regions are usually well adapted to the local agro-ecological and social conditions. There, introduced agricultural innovation geared towards sustainable intensification as a response to changing environments often faces multiple barriers. These may comprise limited market incentives for enhanced production, narrow pathways of knowledge transmission, and infrastructural hurdles. To quantify effects of innovation and sustainable intensification in enhancing smallholders’ livelihoods in the Karakoram Mountains of Northern Pakistan, the present study was conducted with 86 small-holder farmers. We chose interviewees who are involved in the cultivation, processing and/or trading of apricot (Prunus armeniaca L.), a traditionally important currently eroding fruit crop of the Central Asian highlands. By investigating the status quo of apricot production and producers’ innovative farming practices, we generated an intensification index based on simple agronomic indicators. Explanatory farm and framers’ characteristics, production characteristics, knowledge, and apricot management were tested for their predictive power.

Results
Although the data show low average profits of 3.8 US$ tree−1, we found that intensified apricot production can contribute to the provision of nutritious food and increased household income. Age and training of farmers were key factors fostering innovation, while lacking awareness of innovative practices was attributed to slow communication. Rejection of intensification was either due to low-value attribution towards apricot farming or risk aversion. Commonly adopted innovations, particularly sulfur drying, were either well integrated with traditional practices or characterized by low up-front costs and high returns on investment.

Conclusions
Management intensification may increase farmers’ incomes and retard abandonment of apricot farming and the consecutive loss of associated benefits, such as diversified farm output and improved ecosystem services.

Graphical Abstract
Psychometric properties of the arabic translation of the Physical Appearance Comparison Scale-Revised (PACS-R) in adults
Authors: El Khoury Marie Anne , Malaeb Diana , Fawaz Mirna , Chammas Nancy , Soufia Michel , Fekih-Romdhane Feten , Obeid Sahar , Hallit Souheil 
Published: July 2024

Abstract
Background
Physical comparison may be a factor in body dissatisfaction and related issues, like eating disorders and depression. The Physical Appearance Comparison Scale-Revised (PACS-R) is a scale developed to assess the frequency of physical comparison. Because there is no validated scale for body comparison in Arabic, this study aims to address this gap by validating the PACS-R in the Arabic language.

Methods
The PACS-R was translated to Arabic following a conventional forward-backward translation procedure, and was administered to a sample of 359 Lebanese adults along with The Depression Anxiety Stress Scale, and the Rosenberg self-esteem scale (RSES) for convergent validity. The factor structure was studied by confirmatory factor analysis (CFA), and composite reliability was assessed using McDonald’s omega and Cronbach’s alpha.

Results
Results suggested a one-factor structure of the Arabic PACS-R, with good internal consistency (McDonald’s ω = 0.97 / Cronbach α = 0.97). Measurement invariance was established across sex groups, with no significant difference being reported between males and females in terms of PACS-R scores (15.42 ± 10.64 vs. 13.16 ± 11.88; t(357) = 1.84; p = .066). Finally, adequate convergent validity was tested and found to be adequate, with PACS-R scores found to be correlated negatively with self-esteem and positively with psychological distress.

Conclusion
The present findings preliminarily establish the Arabic PACS-R as an effective instrument for researchers and practitioners aiming to explore the physical comparison among Arabic-speaking populations, thus contributing to research and clinical work in the Arabic community.
Accuracy of the national violent death reporting system in identifying unintentional firearm deaths to children by children
Authors: Fischer Samuel , Miller Matthew , Barber Catherine , Azrael Deborah 
Published: July 2024

Abstract
Background
In assigning manner of death (MOD) for inclusion on death certificates, medical examiners and coroners do not always apply uniform criteria. Previous research indicates surveillance statistics based on death certificates, such as the National Vital Statistics System, grossly miscount unintentional firearm deaths. The National Violent Death Reporting System (NVDRS) has taken steps to reduce variability in manner of death coding by providing uniform criteria for assigning an “abstractor manner of death” (AMD). AMD has five categories: unintentional, suicide, homicide, undetermined, and legal intervention homicide. A previous study found good accuracy of AMD coding for unintentional firearm deaths, all ages, 2003–2006, but a more recent study reported that the NVDRS undercounted self- and other-inflicted unintentional firearm deaths in which both the victim and shooter (for other-inflicted injuries) were under age 15 (2009–2018).

Findings
We replicated the recent study’s sample population, identifying 924 NVDRS incidents from 2009 to 2018 in which both victim and, for other-inflicted injuries, shooter age was under 15 and AMD was homicide, suicide, unintentional or undetermined (there were no legal intervention deaths to children). We assigned a researcher-adjudicated MOD (RMD) by reviewing incident narratives. RMD was compared with AMD and with manner recorded on the death certificate. Based on RMD as the gold standard, the sensitivity, specificity, and predictive values positive and negative of the AMD for unintentional childhood firearm deaths were, respectively, 90%, 99%, 98% and 96%; 86% (24/28) of false negatives were coded by abstractors as homicides. By contrast, death certificate manner had relatively poor sensitivity (63%).

Conclusions
In our sample of 924 deaths, the abstractor manner of death generally agreed with researcher-adjudicated manner of death, though not perfectly, missing 10% of researcher-adjudicated unintentional deaths, mostly because abstractors coded these unintentional deaths as homicides. A sizable minority of false negatives were unintentional deaths where the narrative explicitly noted that adult negligence contributed to a child’s unintentional shooting death. While AMD coding in NVDRS is good, it could be improved if NVDRS coding guidelines explicitly affirmed that potential prosecution for negligent manslaughter is not a contraindication to an AMD of unintentional, provided the firearm was not used to intentionally harm, threaten, or coerce.
Hepatopancreatoduodenectomy with delayed division of the pancreatic parenchyma when utilizing a right lateral approach to the superior mesenteric artery
Authors: Hayasaki Aoi , Kuriyama Naohisa , Kaluba Benson , Sakamoto Tatsuya , Komatsubara Haruna , Maeda Koki , Shinkai Toru , Noguchi Daisuke , Ito Takahiro , Gyoten Kazuyuki , Fujii Takehiro , Iizawa Yusuke , Tanemura Akihiro , Murata Yasuhiro , Kishiwada Masashi , Narushima Mitsunaga , Mizuno Shugo 
Published: July 2024

Abstract
Background
Hepatopancreatoduodenectomy (HPD) is a high-risk surgical procedure. Delayed division of the pancreatic parenchyma (DDPP) was reported as a novel technique in HPD for reducing postoperative pancreatic fistula. However, it is often difficult to dissect the pancreatic head nerve plexus while leaving the pancreatic parenchyma intact, particularly in patients with a bulky tumor with vascular invasion. Of the various reported approaches to the superior mesenteric artery, the right lateral approach can provide a useful surgical field to conduct DDPP in HPD.

Case presentation
A 78-year-old man visited a local clinic with itching and jaundice. Laboratory tests revealed elevated hepatobiliary enzyme, total bilirubin, and tumor markers. Enhanced computed tomography, endoscopic retrograde cholangiopancreatography, and intraductal ultrasonography of the bile duct were performed, and he was diagnosed with perihilar cholangiocarcinoma with invasion to the right hepatic artery (40 × 15 mm, Bismuth IIIa, cT3N0M0 cStage III). After neoadjuvant chemotherapy, he underwent left hepatectomy with caudate lobectomy, pancreatoduodenectomy, and combined resection of right hepatic artery using DDPP with a right lateral approach to the superior mesenteric artery. The pathological diagnosis was perihilar cholangiocarcinoma ypT3N1M0 ypStage IIIC, R0 resection. He was discharged on postoperative day 57 in good health and has been doing well for 6 months since the surgery.

Conclusions
We present an effective application of the right lateral approach to the superior mesenteric artery in DDPP during HPD. This procedure can provide a clear surgical field to easily divide the pancreatic head nerve plexus before transection of the pancreatic parenchyma.
3D printed ventilation tubes and their effect on biological models
Authors: Govea-Camacho Luis Humberto , Castillo-López Irma Yolanda , Carbajal-Castillo Sergio Alejandro , Gonzalez-Ojeda Alejandro , Cervantes-Guevara Gabino , Cervantes-Pérez Enrique , Ramírez-Ochoa Sol , Vázquez-Sánchez Sergio Jiram , Delgado-Hernández Gonzalo , Tavares-Ortega Jaime Alberto , González-Muñoz Samantha Emily , Fuentes-Orozco Clotilde 
Published: July 2024

Abstract
Background
Acute otitis media (AOM) causes inflammation and hearing loss. Ventilation tubes are key in treatment. 3D printing improves prostheses in otorhinolaryngology, offering precision and greater adaptability.

Materials and methods
An experimental study was conducted with Wistar rats from July to December 2020. 3D tympanostomy tube models were designed, with technical specifications and tests performed on inexpensive 3D printers. The tympanostomy tube was inserted endoscopically.

Results
Procedures were performed on five rats with implants in both ears. Pre-intervention pathologies, such as atical retraction and glue ear, were found. The PLA-printed tympanostomy tube showed improvement after adjustments. Histopathological results revealed significant middle and inner ear damage.

Conclusion
In our study, the design and 3D printing of implants fulfilled the desired functions when modified, with a height of 5 mm. Complications included PLA degradation and ear damage. There were no adverse events during observation, highlighting the need for further research on 3D-printed implants.
Intraoperative fluid management is not predictive of AKI in major pancreatic surgery: a retrospective cohort study
Authors: Lydon Kerri , Shah Saurin , Mongan Kai L. , Mongan Paul D. , Cantrell Michael Calvin , Awad Ziad 
Published: July 2024

Abstract
Background
Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery.

Methods
This retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018–December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes.

Results
AKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8–35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4–16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality.

Conclusion
In this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.
Identification of common genetic factors and immune-related pathways associating more than two autoimmune disorders: implications on risk, diagnosis, and treatment
Authors: Rajalingam Aruna , Ganjiwale Anjali 
Published: July 2024

AbstractAutoimmune disorders (ADs) are chronic conditions resulting from failure or breakdown of immunological tolerance, resulting in the host immune system attacking its cells or tissues. Recent studies report shared effects, mechanisms, and evolutionary origins among ADs; however, the possible factors connecting them are unknown. This study attempts to identify gene signatures commonly shared between different autoimmune disorders and elucidate their molecular pathways linking the pathogenesis of these ADs using an integrated gene expression approach. We employed differential gene expression analysis across 19 datasets of whole blood/peripheral blood cell samples with five different autoimmune disorders (rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, and type 1 diabetes) to get nine key genes—EGR1, RUNX3, SMAD7, NAMPT, S100A9, S100A8, CYBB, GATA2, and MCEMP1 that were primarily involved in cell and leukocyte activation, leukocyte mediated immunity, IL-17, AGE-RAGE signaling in diabetic complications, prion disease, and NOD-like receptor signaling confirming its role in immune-related pathways. Combined with biological interpretations such as gene ontology (GO), pathway enrichment, and protein–protein interaction (PPI) network, our current study sheds light on the in-depth research on early detection, diagnosis, and prognosis of different ADs.