bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells
Authors: Brunsdon Hannah , Brombin Alessandro , Peterson Samuel , Postlethwait John H. , Patton E. Elizabeth 
Published: April 2022

ABSTRACT
Melanocyte stem cells (McSCs) in zebrafish serve as an on-demand source of melanocytes during growth and regeneration, but metabolic programs associated with their activation and regenerative processes are not well known. Here, using live imaging coupled with scRNA-sequencing, we discovered that, during regeneration, quiescent McSCs activate a dormant embryonic neural crest transcriptional program followed by an aldehyde dehydrogenase (Aldh) 2 metabolic switch to generate progeny. Unexpectedly, although ALDH2 is well known for its aldehyde-clearing mechanisms, we find that, in regenerating McSCs, Aldh2 activity is required to generate formate – the one-carbon (1C) building block for nucleotide biosynthesis – through formaldehyde metabolism. Consequently, we find that disrupting the 1C cycle with low doses of methotrexate causes melanocyte regeneration defects. In the absence of Aldh2, we find that purines are the metabolic end product sufficient for activated McSCs to generate progeny. Together, our work reveals McSCs undergo a two-step cell state transition during regeneration, and that the reaction products of Aldh2 enzymes have tissue-specific stem cell functions that meet metabolic demands in regeneration.
Seasonal changes in membrane structure and excitability in retinal neurons of goldfish (Carassius auratus) under constant environmental conditions
Authors: Country Michael W. , Haase Kristina , Blank Katrin , Canez Carlos R. , Roberts Joshua A. , Campbell Benjamin F. N. , Smith Jeffrey C. , Pelling Andrew E. , Jonz Michael G. 
Published: April 2022

ABSTRACTSeasonal modifications in the structure of cellular membranes occur as an adaptive measure to withstand exposure to prolonged environmental change. Little is known about whether such changes occur independently of external cues, such as photoperiod or temperature, or how they may impact the central nervous system. We compared membrane properties of neurons isolated from the retina of goldfish (Carassius auratus), an organism well adapted to extreme environmental change, during the summer and winter months. Goldfish were maintained in a facility under constant environmental conditions throughout the year. Analysis of whole-retina phospholipid composition using mass spectrometry-based lipidomics revealed a twofold increase in phosphatidylethanolamine species during the winter, suggesting an increase in cell membrane fluidity. Atomic force microscopy was used to produce localized, nanoscale-force deformation of neuronal membranes. Measurement of Young's modulus indicated increased membrane–cortical stiffness (or decreased elasticity) in neurons isolated during the winter. Voltage-clamp electrophysiology was used to assess physiological changes in neurons between seasons. Winter neurons displayed a hyperpolarized reversal potential (Vrev) and a significantly lower input resistance (Rin) compared with summer neurons. This was indicative of a decrease in membrane excitability during the winter. Subsequent measurement of intracellular Ca2+ activity using Fura-2 microspectrofluorometry confirmed a reduction in action potential activity, including duration and action potential profile, in neurons isolated during the winter. These studies demonstrate chemical and biophysical changes that occur in retinal neurons of goldfish throughout the year without exposure to seasonal cues, and suggest a novel mechanism of seasonal regulation of retinal activity.
Do Environmental Regulations Affect the Decision to Export?
Authors: Cherniwchan Jevan , Najjar Nouri 
Published: April 2022

This paper investigates how a common form of environmental regulation—air quality standards—affects exporters. We develop a simple theoretical model to show how the design of these standards causes (i) some firms to stop exporting and (ii) a reduction in the export volumes of affected continuing exporters. We exploit quasi-experimental variation resulting from the design of Canadian air quality standards to test these predictions empirically. Our estimates confirm our model’s predictions: we find that for the most affected manufacturers, regulation reduced export volumes by 32 percent and increased the likelihood plants stop exporting by 5 percentage points. (JEL D12, F14, F18, Q53, Q58)
Effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on podocytes, inflammation, and oxidative stress in patients with diabetic nephropathy (DN)
Authors: Liu Jie , Guo Shanshan , Li Hui , Liu Xu-ying 
Published: April 2022

Objectives: To investigate the effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide on podocytes, inflammation, and oxidative stress in patients with diabetic nephropathy (DN).
Methods: Eighty-four DN patients treated by the department of endocrinology of the Affiliated Hospital of Hebei University during December 2017 and March 2019 were randomly assigned to a control group and a treatment group (n=42, respectively), with the control group prescribed with conventional DN medications and the treatment group receiving liraglutide treatment in addition to the conventional therapy. The course of treatment lasted for 12 weeks. hemoglobin A1c (HbA1C), body mass index (BMI), total cholesterol (TC), triglyceride (TG), urinary albumin excretion rate (UAER), urine podocalyxin (PCX), urine nephrin, as well as inflammation and oxidative stress markers such as tumor necrosis factor α (TNF-α), monocyte chemotactic protein-1 (MCP-1), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured pre- and post-treatment for intergroup comparison.
Results: After 12 weeks of treatment, HbA1C, BMI, TC, and TG in both groups were reduced in comparison with the pre-treatment levels, with the levels in the treatment group lower than in the control group (p<0.05); reduced levels of UAER, PCX, and nephrin were detected in the two groups, with the treatment group exhibiting a significant reduction in these markers compared with the control group (p<0.05); the 12-week treatment led to decreases in the TNF-α, MCP-1, and MDA levels in both groups, with the decline in the treatment group exceeding that in the control group, whereas both groups had an increased level of GSH-Px, with the level in the treatment group higher than that in the control group, and the differences were statistically significant (p<0.05, respectively).
Conclusions: Liraglutide protects the kidneys and improves DN by inhibiting inflammation and oxidative stress, reducing urinary albumin excretion and podocyte damage and supporting renal function in addition to its hypoglycemic properties.
doi: https://doi.org/10.12669/pjms.38.5.4719
How to cite this:Liu J, Guo S, Li H, Liu X. Effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on podocytes, inflammation, and oxidative stress in patients with diabetic nephropathy (DN). Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.4719
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Clinical Effects of MOTOmed Intelligent Exercise Training Combined with Intensive Walking Training on the Rehabilitation of Walking, Nerve and Lower Limb Functions among Patients with Hemiplegia after Stroke
Authors: Hu Yajing , Tian Jingjing , Wen Xiaoliang , Lu Can , Tian Ningning 
Published: April 2022

Objectives: To investigate the clinical effects of MOTOmed intelligent exercise training combined with intensive walking training on the rehabilitation of walking, nerve and lower limb functions among patients with hemiplegia after stroke.
Methods: Randomized controlled trial was used in this study. Fifty-two patients with hemiplegia after stroke treated in 82nd Army Group Military Hospital from February 2017 to February 2018 were selected as the subjects and randomly divided into the control group and the observation group, each with 26 cases. The control group underwent intensive walking training, and the observation group underwent MOTOmed intelligent exercise training on the control group basis. Both groups’ rehabilitation of walking function, nerve function and lower limb function were observed.
Results: Both groups had significantly increased FAC score and 10-m maximum walking speed (P < 0.05), and the observation group had significantly higher results than those of the control group (P < 0.05); both groups had significantly higher FMA scores than before treatment (P < 0.05), and the observation group had significantly higher scores than those of the control group (P < 0.05); both groups after two months of treatment had significantly increased NGF, NT-3 and BDNF (P<0.05), and the observation group had significantly higher levels than those of the control group (P<0.05).
Conclusion: MOTOmed intelligent exercise training combined with intensive walking training can significantly improve the walking function, nerve function and lower limb function among patients with hemiplegia after stroke.
doi: https://doi.org/10.12669/pjms.38.5.5259
How to cite this:Hu Y, Tian J, Wen X, Lu C, Tian N. Clinical Effects of MOTOmed Intelligent Exercise Training Combined with Intensive Walking Training on the Rehabilitation of Walking, Nerve and Lower Limb Functions among Patients with Hemiplegia after Stroke. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5259
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Associations among smoking, IDH mutations, MGMT promoter methylation, and grading in glioma: a cross-sectional study
Authors: Malueka Rusdy Ghazali , Hartanto Rachmat Andi , Alethea Maria , Sianipar Christina Megawimanti , Wicaksono Adiguno Suryo , Basuki Endro , Dananjoyo Kusumo , Asmedi Ahmad , Dwianingsih Ery Kus 
Published: April 2022

Background Several molecular markers have important roles in glioma management. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with the grading and prognosis of glioma. Methylation in the promoter region of the O (6)-methylguanine-DNA methyltransferase (MGMT) gene is an important determinant of glioma sensitivity to alkylating agents. Studies in various cancers indicated that IDH1 mutations and MGMT promoter methylations were associated with smoking habits. However, these associations in gliomas are still unclear. Accordingly, this study aimed to examine the association among smoking, IDH1 mutations, MGMT promoter methylation, and grading in glioma patients. Methods Patients were recruited from Dr. Sardjito General Hospital (a referral hospital in Yogyakarta and Central Java region) and its network hospitals. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples or fresh glioma tissues. Identification of IDH1 mutation was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or DNA sequencing. Methylation-specific real-time PCR was performed to identify MGMT promoter methylation status. Smoking status was obtained by history taken from the patient or family members. Results In total, 122 patients were included in this study. As many as 35 patients (28.7%) had a smoking history. Most smokers (57.1%) smoke less than ten cigarettes per day. However, most of them (68.8%) have been smoking for more than 20 years. Smoking patients have a significantly higher proportion of high-grade glioma than non-smokers (80% vs. 55.2%, p=0.01). Among 122 patients, 24 (19.7%) of them carried IDH1 mutation. Smoking patients have a significantly higher proportion of IDH1 mutation compared with non-smokers (31.4% vs. 14.9%, p<0.001). No significant association was found between intensity and duration of smoking with IDH1 mutations and glioma grading. No significant association was found between smoking and MGMT promoter methylation. Conclusions In glioma patients, smoking is associated with IDH1 mutations and grading but not with MGMT promoter methylation.
Development and implementation of a tool for measuring the training effectiveness of the patient-centered consultation model
Authors: Jorgensen Merete , Thorsen Hanne , Siersma Volkert , Winther Bang Christine 
Published: April 2022

Background: The patient-centered consultation model comprises four elements: exploring health, illness and disease experiences, understanding the whole person, finding common ground, and enhancing the patient-doctor relationship. This method is taught at the course in general practice at Copenhagen University. The aim of the study was to develop a simple tool consisting of a questionnaire about the patient-centered elements and a test video consultation. The outcome is the change in the students’ ability to identify these elements. Used as a pre-course and post-course test it can inform the teachers which elements of the patient-centered consultation need intensifying in the teaching. Methods: The students from a course in general practice volunteered to participate in all steps of the development. They took part in individual interviews to select items from an already existing questionnaire (DanSCORE). The preliminary questionnaire was tested for face and content validity, pilot-tested and tested for test-retest reliability. All video consultations were transcribed and assessed for patient-centered elements through a conversation analysis. The videos showed medical students seeing real patients. Results: The preliminary version of the questionnaire (called DanOBS) had 23 items. In the subsequent interviews, items were reduced to 17, each with three response options. After a pilot test, the questionnaire was further reduced to 13 items, all strictly relevant to the model and with two response options. The final questionnaire had acceptable test-retest reliability. The number of test consultation videos underwent a reduction from six videos to one. Conclusions: The DanOBS combined with a test video consultation, used as a pre-and post-course test demonstrates for teachers which elements in the patient-centered consultation need to be intensified in the teaching.
The benefits of index telephone consultations in patients referred on the two-week wait colorectal cancer pathway
Authors: Wanigasooriya K , Sarma DR , Woods P , O’Connor P , Matthews A , Aslam MI , Dando C , Ferguson H , Francombe J , Lal N , Murphy PD , Papettas T , Ramcharan S , Busby K 
Published: April 2022

Introduction The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) clinic appointments, conducted using telephone calls at a district general hospital in England. Methods Patients undergoing index outpatient 2-ww LGI clinic assessment between 1 June 2019 and 31 October 2019 (FtF group) and 1 June 2020 and 31 October 2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets was assessed. Environmental and financial impact analyses were performed. Results In total, 1,531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF (n=774, 50.6%). Ninety-two (6%, VC=44, FtF=48) patients had malignant pathology and 64 (4.2%) had colorectal cancer (CRC); of these, 46 (71.9%, VC=26, FtF=20) underwent treatment with curative intent. The median waiting times to index appointment, investigation and diagnosis were significantly lower following VC assessment (p<0.001). The cancer detection rates (p=0.749), treatments received (p=0.785) and median time to index treatment for CRC patients (p=0.156) were similar. A significantly higher proportion of patients were seen within two weeks of referral in the VC group (p<0.001). VC appointments saved patients a total of 9,288 miles, 0.7 metric tonnes of CO2 emissions and £7,482.97. Taxpayers saved £80,242.00 from VCs. No formal complaints were received from patients or staff in the VC group. Conclusion Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits.
Impact of visual impairment on balance and visual processing functions in students with special educational needs
Authors: Choi Kai Yip , Wong Ho Yin , Cheung Hoi Nga , Tseng Jung Kai , Chen Ching Chung , Wu Chieh Lin , Eng Helen , Woo George C. , Cheong Allen Ming Yan 
Published: April 2022

Introduction
Vision is critical for children’s development. However, prevalence of visual impairment (VI) is high in students with special educational needs (SEN). Other than VI, SEN students are prone to having functional deficits. Whether visual problems relate to these functional deficits is unclear. This study aimed to assess the impact of vision on visual processing functions and balance in SEN students through a community service.

Methods
Visual acuity (VA) and contrast sensitivity were measured in a total of 104 (aged 14.3±4.3) SEN students as the visual outcomes, followed by retinoscopy. Visual processing function assessment included facial expression recognition by card matching examiner’s facial expression matching, and visual orientation recognition. Dynamic balance, by Timed Up and Go test, and static standing balance (postural sway in double-legged standing with feet-together and tandem-stance for open-eye and closed-eye conditions) were assessed. Static balance was presented in terms of the maximal medial-lateral and antero-posterior sways.

Results
Of the 104 students, 62 (59.6%) were classified as visually impaired according to WHO classification of visual impairment based on presenting distance acuity. Ocular problems (e.g. optic nerve anomaly, uncorrected/ under-corrected refractive errors) and neurological anomalies were the major causes of vision loss. VA was positively associated with visual processing functions (all p ≤ 0.01), as SEN students with better vision tended to perform better in visual orientation and facial expression recognition tasks, as well as dynamic balance function (p = 0.04). For the static balance, postural sway and VA showed a positive relationship under open-eye and tandem stance conditions. However, the relationship between postural sway and VA became negative under closed-eye and tandem stance conditions.

Conclusion
This study found a high prevalence of SEN students with visual impairment, in which many of them were undetected. Optometric examination is important to improve their visual function to minimize the effect of vision on functional performance. Vision is critical in visual processing as well as playing an important role in maintaining balance in SEN students.
Comparative analysis of cardio-cerebrovascular complications in immigrants and native-born Koreans with diabetes: Risk factors and perspectives
Authors: Cho Hyemin , Jeoung Sohyun , Kang Cinoo , Jang Sunmee 
Published: April 2022

BackgroundGiven the rapidly increasing number of immigrants, it is crucial to address health care issues involving immigrants to facilitate their safe and secure settlement. Especially for common chronic diseases, such as diabetes, immigrants face more complex obstacles to manage their chronic conditions than do native-born residents. Therefore, we aimed to assess differences in the incidence and associated risk factors of cardio-cerebrovascular (CCV) complications of immigrants compared with native-born Koreans with diabetes.MethodsImmigrants and native-born Koreans who had new diagnosis of diabetes and simultaneously received anti-diabetic prescriptions in 2012 were defined by using Korean National Health Insurance Claim Database(KNHICD). CCV complications were assessed at a 3-year follow-up from the index date. We assessed differences in the CCV complications and risk factors using multiple cox regression models.ResultsIn total, 4,008 patients (668 of immigrants and 3,340 of native-born Koreans) who had newly diagnosed diabetes and simultaneously received anti-diabetic prescriptions in 2012 were selected. Immigrants with diabetes were at a 1.39 times higher risk of having CCV complications than native-born Koreans with diabetes (95% CI: 1.021–1.881). Patients who had a usual sources of care (USC) presented a significantly reduced risk of cardio-cerebrovascular complication (HR: 0.452; 95% CI: 0.342–0.598) in both immigrants and native Koreans. In subgroup analysis in immigrants, patients having USC showed decreased risk of CCV incidence (HR: 0.35, 95% CI: 0.175–0.703), whereas >60 years old and Charlson comorbidity index (CCI) score >1 presented increased risk of CCV complications.ConclusionImmigrants with diabetes have a higher risk of CCV complications than native-born Koreans with diabetes. However, having a USC significantly decreased the risk of CCV complications. Therefore, the utilization of USC will benefit to reduce diabetic complications in immigrants as well as reduction of overall health care cost burden, it would be necessary to implement USC in diabetes care at the initial disease stage.
Using machine learning for the personalised prediction of revision endoscopic sinus surgery
Authors: Nuutinen Mikko , Haukka Jari , Virkkula Paula , Torkki Paulus , Toppila-Salmi Sanna 
Published: April 2022

Background
Revision endoscopic sinus surgery (ESS) is often considered for chronic rhinosinusitis (CRS) if maximal conservative treatment and baseline ESS prove insufficient. Emerging research outlines the risk factors of revision ESS. However, accurately predicting revision ESS at the individual level remains uncertain. This study aims to examine the prediction accuracy of revision ESS and to identify the effects of risk factors at the individual level.

Methods
We collected demographic and clinical variables from the electronic health records of 767 surgical CRS patients ≥16 years of age. Revision ESS was performed on 111 (14.5%) patients. The prediction accuracy of revision ESS was examined by training and validating different machine learning models, while the effects of variables were analysed using the Shapley values and partial dependence plots.

Results
The logistic regression, gradient boosting and random forest classifiers performed similarly in predicting revision ESS. Area under the receiving operating characteristic curve (AUROC) values were 0.744, 0.741 and 0.730, respectively, using data collected from the baseline visit until six months after baseline ESS. The length of time during which data were collected improved the prediction performance. For data collection times of 0, 3, 6 and 12 months after baseline ESS, AUROC values for the logistic regression were 0.682, 0.715, 0.744 and 0.784, respectively. The number of visits before or after baseline ESS, the number of days from the baseline visit to the baseline ESS, patient age, CRS with nasal polyps (CRSwNP), asthma, non-steroidal anti-inflammatory drug exacerbated respiratory disease and immunodeficiency or suspicion of it all associated with revision ESS. Patient age and number of visits before baseline ESS carried non-linear effects for predictions.

Conclusions
Intelligent data analysis identified important predictors of revision ESS at the individual level, such as the frequency of clinical visits, patient age, Type 2 high diseases and immunodeficiency or a suspicion of it.