bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxycycline-dependent Cas9-expressing pig resources for conditional in vivo gene nullification and activation
Authors: Jin Qin , Liu Xiaoyi , Zhuang Zhenpeng , Huang Jiayuan , Gou Shixue , Shi Hui , Zhao Yu , Ouyang Zhen , Liu Zhaoming , Li Lei , Mao Junjie , Ge Weikai , Chen Fangbing , Yu Manya , Guan Yezhi , Ye Yinghua , Tang Chengcheng , Huang Ren , Wang Kepin , Lai Liangxue 
Published: January 2023

Abstract
Background
CRISPR-based toolkits have dramatically increased the ease of genome and epigenome editing. SpCas9 is the most widely used nuclease. However, the difficulty of delivering SpCas9 and inability to modulate its expression in vivo hinder its widespread adoption in large animals.

Results
Here, to circumvent these obstacles, a doxycycline-inducible SpCas9-expressing (DIC) pig model was generated by precise knock-in of the binary tetracycline-inducible expression elements into the Rosa26 and Hipp11 loci, respectively. With this pig model, in vivo and/or in vitro genome and epigenome editing could be easily realized. On the basis of the DIC system, a convenient Cas9-based conditional knockout strategy was devised through controlling the expression of rtTA component by tissue-specific promoter, which allows the one-step generation of germline-inherited pigs enabling in vivo spatiotemporal control of gene function under simple chemical induction. To validate the feasibility of in vivo gene mutation with DIC pigs, primary and metastatic pancreatic ductal adenocarcinoma was developed by delivering a single AAV6 vector containing TP53-sgRNA, LKB1-sgRNA, and mutant human KRAS gene into the adult pancreases.

Conclusions
Together, these results suggest that DIC pig resources will provide a powerful tool for conditional in vivo genome and epigenome modification for fundamental and applied research.
The impact of different researchers to capture quality of life measures in a dementia randomised controlled trial
Authors: Evans Rachel , Brocklehurst Paul , Ryan Jean , Hoare Zoë 
Published: January 2023

Abstract
Background
Capturing changes in health and wellbeing within randomised controlled trials (RCTs) can be complex. The precision and accuracy of outcome scales to measure change is crucial, and therefore, consideration needs to be given to potential measurement errors when collecting these outcomes.
Many RCTs use multiple researchers to collect data, which has the potential to introduce variation in measurements. This study aimed to identify if there was a measurable effect of using different researchers to collect repeated assessments of quality of life (QoL) at different time points.

Methods
A previously conducted study assessing the impact of reminiscence therapy on participants with dementia and carer (PwD-carer) dyads, ‘REMCARE’ (Reminiscence groups for people with dementia and their family caregivers), provided the platform for this exploratory secondary analysis. Data was categorised into two broad groups: those where the same researcher attended all assessments and those where different researchers undertook the assessments. ANCOVA (analysis of covariance) models used in the original REMCARE analysis with the addition of the ‘researcher-continuity’ variable were run on two QoL measures, the QoL-AD (Quality of Life in Alzheimer’s Disease) and QCPR (Quality of the Caregiving Relationship).

Results
Three hundred thirty PwD-carer dyads were included in the analysis. For the PwD, a statistically significant effect was found on the researcher continuity variable for the QoL-AD and QCPR outcome measures at follow-up 1 but not at follow-up 2 signifying an impact of researcher attendance at the first follow-up but not follow-up 2. For the carer data, analyses revealed no statistically significant effects at follow-up 1; however, the QoL-AD measure at follow-up 2 was found to be statistically significant.

Conclusions
These exploratory results indicate the possible impact of researcher continuity on QoL outcomes in dementia studies. Further research is required to explore this further and establish causality. If demonstrated, this would have implications for the planning of future empirical studies in dementia, in order to reduce this potential source of bias.
The effect of bitter almond (Amygdalus communis L. var. Amara) gum as a functional food on metabolic profile, inflammatory markers, and mental health in type 2 diabetes women: a blinded randomized controlled trial protocol
Authors: Saati Saba , Dehghan Parvin , Azizi-Soleiman Fatemeh , Mobasseri Majid 
Published: January 2023

Abstract
Background
Using functional foods in the prevention and treatment of type 2 diabetes mellitus (T2DM) has increased across the world owing to their availability, cultural acceptability, and lower side effects. The present study will aim to examine the impact of bitter almond (Amygdalus communis L. var. Amara) gum as a functional food on metabolic profile, inflammatory markers, and mental health in women with T2DM.

Methods
We will conduct a randomized, triple-blind, placebo-controlled trial. A total of 44 women with T2DM will be randomly allocated into two groups: an intervention group (n = 20) and a placebo group (n = 20). Patients will receive either 5 g/d of bitter melon gum or a placebo for 8 weeks. Clinical and biochemical outcome parameters which include glycemic indices, lipid profile, inflammatory markers, oxidative stress indices, tryptophan (Trp), kynurenine (KYN), cortisol, glucagon-like peptide 1 (GLP-1), leptin, adiponectin, ghrelin, peroxisome proliferator-activated receptor (PPAR) gene expression, brain-derived neurotrophic factor (BDNF), endothelial cell adhesion molecules, plasminogen, cluster deference 4 (CD4), cluster deference 8 (CD8), anthropometric indices, blood pressure, dietary intake, and mental health will be measured at the baseline and end of the study. Statistical analysis will be conducted using the SPSS software (version 24), and P value less than 0.05 will be considered statistically significant.

Discussion
The present randomized controlled trial will aim to investigate any beneficial effects of bitter almond gum supplementation on the cardio-metabolic, immune-inflammatory, and oxidative stress biomarkers, as well as mental health in women with T2DM.

Ethics and dissemination
The study protocol was approved by the Ethical Committee of the Tabriz University of Medical Sciences (IR.TBZMED.REC.1399.726).

Trial registration
Iranian Registry of Clinical Trials (www.irct.ir/IRCT20150205020965N7)
Bioconversion of non-food corn biomass to polyol esters of fatty acid and single-cell oils
Authors: Liu Guang-Lei , Bu Xian-Ying , Chen Chaoyang , Fu Chunxiang , Chi Zhe , Kosugi Akihiko , Cui Qiu , Chi Zhen-Ming , Liu Ya-Jun 
Published: January 2023

Abstract
Background
Lignocellulose is a valuable carbon source for the production of biofuels and biochemicals, thus having the potential to substitute fossil resources. Consolidated bio-saccharification (CBS) is a whole-cell-based catalytic technology previously developed to produce fermentable sugars from lignocellulosic agricultural wastes. The deep-sea yeast strain Rhodotorulapaludigena P4R5 can produce extracellular polyol esters of fatty acids (PEFA) and intracellular single-cell oils (SCO) simultaneously. Therefore, the integration of CBS and P4R5 fermentation processes would achieve high-value-added conversion of lignocellulosic biomass.

Results
The strain P4R5 could co-utilize glucose and xylose, the main monosaccharides from lignocellulose, and also use fructose and arabinose for PEFA and SCO production at high levels. By regulating the sugar metabolism pathways for different monosaccharides, the strain could produce PEFA with a single type of polyol head. The potential use of PEFA as functional micelles was also determined. Most importantly, when sugar-rich CBS hydrolysates derived from corn stover or corncob residues were used to replace grain-derived pure sugars for P4R5 fermentation, similar PEFA and SCO productions were obtained, indicating the robust conversion of non-food corn plant wastes to high-value-added glycolipids and lipids. Since the produced PEFA could be easily collected from the culture via short-time standing, we further developed a semi-continuous process for PEFA production from corncob residue-derived CBS hydrolysate, and the PEFA titer and productivity were enhanced up to 41.1 g/L and 8.22 g/L/day, respectively.

Conclusions
Here, we integrated the CBS process and the P4R5 fermentation for the robust production of high-value-added PEFA and SCO from non-food corn plant wastes. Therefore, this study suggests a feasible way for lignocellulosic agro-waste utilization and the potential application of P4R5 in industrial PEFA production.
Assessment ameliorative role of fenugreek seeds and germinated fenugreek seeds on pancreatic and testicular gentamicin toxicity of male Swiss albino mice
Authors: Hamad Sherin Ramadan , Anwar Hend M. , Diab Marwa S. M. 
Published: January 2023

Abstract
Background
Gentamicin is one of aminoglycoside antibiotic used for treatment of many infections due to its availability and less cost. The aim of this study aimed to assess the modulation effect of fenugreek seed and its germinated seeds on pancreatic and testicular toxicity induced by gentamicin in male Swiss albino mice. Forty male albino mice were divided into four treatment groups as follows: (1) control group, (2) gentamicin treated group, (3) gentamicin-fenugreek treated group and (4) gentamicin-germinated fenugreek treated group. Pancreatic and testicular tissues were collected for histopathological examinations, histochemical, and biochemical analysis as well as genetic study.

Results
Administration of gentamicin resulted in histopathological damage in pancreatic and testicular tissues as well as decreased glutathione peroxides, catalase and total antioxidant activity content in both pancreatic and testicular tissues compared to control group. Histopathological changes and antioxidant/oxidative alterations as well as DNA damage observed in gentamicin treated animals found were moderate improvement by fenugreek seeds administration and marked improvement by treatment with germinated fenugreek seeds.

Conclusions
Treated with gentamicin induced histopathological lesions, antioxidant/oxidant imbalance and DNA damage in the pancreatic and testicular. Treatment with germinated fenugreek seeds was more effective than fenugreek seeds in amelioration of pancreatic and testicular lesions, preventing high appearance of carbohydrate and accumulation of collagen fibers as well as oxidative damage and genotoxicity induced by gentamicin administration.
Implementation, uptake and use of a digital COVID-19 symptom tracker in English care homes in the coronavirus pandemic: a mixed-methods, multi-locality case study
Authors: Nelson Pauline A. , Bradley Fay , Ullah Akbar , Whittaker Will , Brunton Lisa , Calovski Vid , Money Annemarie , Dowding Dawn , Cullum Nicky , Wilson Paul 
Published: January 2023

AbstractBackgroundCOVID-19 spread rapidly in UK care homes for older people in the early pandemic. National infection control recommendations included remote resident assessment. A region in North-West England introduced a digital COVID-19 symptom tracker for homes to identify early signs of resident deterioration to facilitate care responses. We examined the implementation, uptake and use of the tracker in care homes across four geographical case study localities in the first year of the pandemic.MethodsThis was a rapid, mixed-methods, multi-locality case study. Tracker uptake was calculated using the number of care homes taking up the tracker as a proportion of the total number of care homes in a locality. Mean tracker use was summarised at locality level and compared. Semi-structured interviews were conducted with professionals involved in tracker implementation and used to explore implementation factors across localities. Template Analysis with the Consolidated Framework for Implementation Research (CFIR) guided the interpretation of qualitative data.ResultsUptake varied across the four case study localities ranging between 13.8 and 77.8%.Tracker use decreased in all localities over time at different rates, with average use ranging between 18 and 58%. The implementation context differed between localities and the process of implementation deviated over time from the initially planned strategy, for stakeholder engagement and care homes’ training. Four interpretative themes reflected the most influential factors appearing to affect tracker uptake and use: (1) the process of implementation, (2) implementation readiness, (3) clarity of purpose/perceived value and (4) relative priority in the context of wider system pressures.ConclusionsOur study findings resonate with the digital solutions evidence base prior to the COVID-19 pandemic, suggesting three key factors that can inform future development and implementation of rapid digital responses in care home settings even in times of crisis: an incremental approach to implementation with testing of organisational readiness and attention to implementation climate, particularly the innovation’s fit with local contexts (i.e. systems, infrastructure, work processes and practices); involvement of end-users in innovation design and development; and enabling users’ easy access to sustained, high-quality, appropriate training and support to enable staff to adapt to digital solutions.
Carbon dots as fluorescent nanoprobes for assay of some non-fluorophoric nitrogenous compounds of high pharmaceutical interest
Authors: Moustafa Rana M. , Talaat Wael , Youssef Rasha M. , Kamal Miranda F. 
Published: January 2023

Abstract
Background
Carbon dots, CDs, have excellent photoluminescence properties, good biocompatibility, low toxicity and good light stability. The optical, magnetic and electronic properties of CDs make them a hugely relevant tool to be used in pharmaceutical analysis, bioimaging, drug delivery, and other fields. The fluorescence of carbon nanodots makes it suitable for assay of some nitrogenous compounds of high pharmaceutical interest. In this work, we develop simple, fast and green spectrophotometric methods for quantification of Azithromycin and Rasagiline mesilate using synthesized fluorescent CDs from garlic peels.

Results
The spectrometric methods depend on stoichiometric reactions of both drugs with fluorescent CDs. Carbon dots exhibit a declared absorption peak λmax at 238 nm and potent fluorimetric emission at λem 528 nm, upon excitation at λex 376 nm. Drugs’ concentrations in ppm are efficiently calculated using Stern–Volmer Equation. Decrease in fluorescence (ΔF = Fo − F) and the F-ratio values are linearly correlated to molar concentration of each quencher (drug). A significant linear diminish in the dots’ measured absorbance and fluorimetric emission values was observed. Validation of all the developed methods was according to the ICH guidelines.

Conclusions
In a new way, this work successfully indicates, spectrometric methods for rapid detection of two non-fluorophoric nitrogenous compounds using potent carbon nanodots. Consequently, these green developed methods offer several benefits as simplicity, ease of quantification, accuracy and precision that encourage the application of the developed methods in routine analysis of Azithromycin and Rasagiline mesilate in quality control laboratories as analytical tool.
The value of frontal sinusotomy in cases of sinonasal polyposis
Authors: Yousef Ahmed , Elkadeem Osama Abdelnaseer , Ashry Hossam Mohamed , Eldehn Ahmed Fathy 
Published: January 2023

Abstract
Background
Chronic frontal sinusitis is being treated with less invasive transnasal endoscopic treatments. Surgery relieves illness and prevents recurrence. Our study was conducted on 80 patients who suffer from frontal opacity with sinonasal polyposis and divided randomly into 2 groups: group A: 40 patients candidate for anterior ethmoidectomy without identification of frontal sinus ostium and group B: 40 patients candidate for anterior ethmoidectomy with identification of frontal sinus ostium. The study was conducted in the otolaryngology department faculty of medicine Cairo university.

Results
CT score and sinonasal endoscopy score were statistically significantly improved postoperatively compared to preoperative scores in both groups. There are no significant differences between the 2 groups regarding recurrence rate and complications.

Conclusion
Ethmoidectomy without frontal sinusotomy is a potential substitute for frontal sinusotomy for the treatment of chronic frontal sinusitis with sinonasal polyposis, and it can achieve similar improvements in symptoms and radiological evidence of frontal sinusitis.
Implementation of a Telehealth Genetic Testing Station to Deliver Germline Testing for Men With Prostate Cancer
Authors: Kwon Daniel H. , Gordon Kelly M. , Tong Barry , Borno Hala T. , Beigh Makenna , Fattah Delaire , Schleicher Alexandra , Aggarwal Rahul R. , Blanco Amie M. , Small Eric J. , Dhawan Mallika 
Published: January 2023

PURPOSE: Germline testing for men with prostate cancer (PCa) poses numerous implementation barriers. Alternative models of care delivery are emerging, but implementation outcomes are understudied. We evaluated implementation outcomes of a hybrid oncologist– and genetic counselor–delivered model called the genetic testing station (GTS) created to streamline testing and increase access. METHODS: A prospective, single-institution, cohort study of men with PCa referred to the GTS from October 14, 2019, to October 14, 2021, was conducted. Using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, we described patients referred to GTS (Reach), the association of GTS with germline testing completion rates within 60 days of a new oncology appointment in a pre- versus post-GTS multivariable logistic regression (Effectiveness), Adoption, Implementation, and Maintenance. Because GTS transitioned from an on-site to remote service during the COVID-19 pandemic, we also compared outcomes for embedded versus remote GTS. RESULTS: Overall, 713 patients were referred to and eligible for GTS, and 592 (83%) patients completed germline testing. Seventy-six (13%) patients had ≥ 1 pathogenic variant. Post-GTS was independently associated with higher odds of completing testing within 60 days than pre-GTS (odds ratio, 8.97; 95% CI, 2.71 to 29.75; P < .001). Black race was independently associated with lower odds of testing completion compared with White race (odds ratio, 0.35; 95% CI, 0.13 to 0.96; P = .042). There was no difference in test completion rates or patient-reported decisional conflict for embedded versus remote GTS. GTS has been adopted by 31 oncology providers across four clinics, and implementation fidelity was high with low patient loss to follow-up, but staffing costs are a sustainability concern. CONCLUSION: GTS is a feasible, effective model for high-volume germline testing in men with PCa, both in person and using telehealth. GTS does not eliminate racial disparities in germline testing access.
Waterhouse-Friderichsen Syndrome and Central Diabetes Insipidus Due to Escherichia coli Meningitis
Authors: Mizuno Shinsuke , Yokoyama Koji , Nukada Takayuki , Hara Shigeto 
Published: January 2023

Abstract
Waterhouse-Friderichsen syndrome and central diabetes insipidus are uncommon but potentially fatal endocrine and metabolic diseases. Waterhouse-Friderichsen syndrome is defined as adrenal insufficiency caused by adrenal hemorrhage, which is typically bilateral and most frequently due to meningococcal infection. It is usually diagnosed by necropsy. Central diabetes insipidus in children is often caused by trauma, intracranial lesions, autoimmune diseases, and infections. In addition, it can be caused by mutations in the AVP-NPII gene, although this occurs typically later in childhood rather than in the neonatal period. This report describes a term infant who developed Escherichia coli meningitis, which resulted in septic shock and disseminated intravascular coagulation. Abdominal ultrasound led to an early diagnosis of bilateral adrenal hemorrhage and appropriate treatment with corticosteroids. Symptomatic central diabetes insipidus developed a few days after the onset of meningitis. Intravenous vasopressin was effective in resolving hemodynamic instability. In conclusion, sepsis and meningitis may have severely affected the endocrine system in this patient. Early diagnosis and appropriate treatment for both diseases may have resulted in better clinical outcomes for this patient.
The experience of using Alpha-Stim AID cranial electrotherapy stimulation (CES) for symptoms of anxiety
Authors: Griffiths Chris , Walker Kate , Jiang Harmony 
Published: January 2023

Background: Alpha-Stim AID is a self-administered, cranial electrotherapy stimulation (CES) device with evidence of effectiveness in treating symptoms of anxiety. In this study, Alpha-Stim AID was offered through a United Kingdom (UK) primary care social prescription service to patients with symptoms of anxiety. This study explored the experience and impact of using Alpha-Stim AID cranial electrotherapy stimulation (CES) through in-depth interviews. Methods: Out of a sample of 57 using Alpha-Stim AID, fifteen participants consented to be interviewed. The age range of the participants was 26–65 years (M = 46.6); 10 (67%) were female and 5 (33%) male. Data were analysed using thematic analysis. Results: There was support for the acceptability and useability of Alpha-Stim AID. Most participants described a positive impact in their lives and would recommend it to others. Themes that emerged offered insights into how people used the Alpha-Stim and their experiences of the effects. Conclusions: It is important to identify anxiety symptoms and offer patients choice of treatment options. The results support the use of Alpha-Stim AID as a treatment option for people with symptoms of anxiety. Access to Alpha-Stim AID should not be restricted by being able to afford to buy it. An appropriately designed randomised control trial (RCT) is required.