bluuebunny/crossref_metadata_2025 huggingface dataset:
Early prediction of pathological complete response to neoadjuvant chemotherapy combining DCE-MRI and apparent diffusion coefficient values in breast Cancer
Authors: Liang Xinhong , Chen Xiaofeng , Yang Zhiqi , Liao Yuting , Wang Mengzhu , Li Yulin , Fan Weixiong , Dai Zhuozhi , Zhang Yunuo
Published: December 2022

Introduction

Improving the early prediction of neoadjuvant chemotherapy (NAC) efficacy in breast cancer can lead to an improved prediction of the final prognosis of patients, which would be useful for promoting individualized treatment. This study aimed to explore the value of the combination of dynamic contrast-enhanced (DCE)-MRI parameters and apparent diffusion coefficient (ADC) values in the early prediction of pathological complete response (pCR) to NAC for breast cancer.

Methods

A total of 119 (range, 28−69 years) patients with biopsy-proven breast cancer who received two cycles of NAC before breast surgery were retrospectively enrolled from our hospital database. Patients were divided into pCR and non pCR groups according to their pathological responses; a total of 24 patients achieved pCR, while 95 did not. The quantitative (Ktrans; Kep; Ve; IAUC) and semiquantitative parameters (W-in; W-out; TTP) of DCE-MRI that were significantly different between groups were combined with ADC values to explore their value in the early prediction of pCR to NAC for breast cancer. The independent T test was performed to compare the differences in DCE-MRI parameters and ADC values between the two groups. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC), sensitivity and specificity were calculated to evaluate the performance of the prediction.

Results

The Ktrans, Kep, IAUC, ADC, W-in and TTP values were significantly different between the pCR and non pCR groups after NAC. The AUC (0.845) and specificity (95.79%) of the combined Ktrans, Kep, IAUC and ADC values were both higher than those of the individual parameters. The combination of W-in, TTP and ADC values had the highest AUC value (0.886) in predicting pCR, with a sensitivity and specificity of 87.5% and 82.11%, respectively.

Conclusions

The results suggested that the combination of ADC values and quantitative and semiquantitative DCE-MRI parameters, especially the combination of W-in, TTP, and ADC values, may improve the early prediction of pCR in breast cancer.
Eribulin normalizes pancreatic cancer-associated fibroblasts by simulating selected features of TGFβ inhibition
Authors: Luong Tiffany , Cukierman Edna
Published: December 2022

Background

Less than 11% of pancreatic cancer patients survive 5-years post-diagnosis. The unique biology of pancreatic cancer includes a significant expansion of its desmoplastic tumor microenvironment, wherein cancer-associated fibroblasts (CAFs) and their self-produced extracellular matrix are key components. CAF functions are both tumor-supportive and tumor-suppressive, while normal fibroblastic cells are solely tumor-suppressive. Knowing that CAF-eliminating drugs are ineffective and can accelerate cancer progression, therapies that “normalize” CAF function are highly pursued. Eribulin is a well-tolerated anti-microtubule drug used to treat a plethora of neoplasias, including advanced/metastatic cancers. Importantly, eribulin can inhibit epithelial to mesenchymal transition via a mechanism akin to blocking pathways induced by transforming growth factor-beta (TGFβ). Notably, canonical TGFβ signaling also plays a pivotal role in CAF activation, which is necessary for the development and maintenance of desmoplasia. Hence, we hypothesized that eribulin could modulate, and perhaps “normalize” CAF function.

Methods

To test this premise, we used a well-established in vivo-mimetic fibroblastic cell-derived extracellular matrix (CDM) system and gauged the effects of eribulin on human pancreatic CAFs and cancer cells. This pathophysiologic fibroblast/matrix functional unit was also used to query eribulin effects on CDM-regulated pancreatic cancer cell survival and invasive spread.

Results

Demonstrated that intact CAF CDMs modestly restricted eribulin from obstructing pancreatic cancer cell growth. Nonetheless, eribulin-treated CAFs generated CDMs that limited nutrient-deprived pancreatic cancer cell survival, similar to reported tumor-suppressive CDMs generated by TGFβ-deficient CAFs.

Conclusions

Data from this study support the central proposed premise suggesting that eribulin could be used as a CAF/matrix-normalizing drug.
Prevalence, predictors and consequences of gambling on Children in Ghana
Authors: Kyei-Gyamfi Sylvester , Coffie Daniel , Abiaw Michael Ofori , Hayford Patience , Martey Joseph Otchere , Kyei-Arthur Frank
Published: December 2022

Background

Gambling is illegal for children in Ghana. However, young people, including children, are increasingly engaged in gambling across the country. Gambling is harmful and poses developmental implications for the youth, including children. There are limited studies on child gambling in Ghana and other sub-Saharan African countries. This study examined the prevalence of gambling participation, predictors of gambling participation, and perceived harm of gambling on children.

Methods

A cross-sectional convergent parallel mixed methodology was used to study 5024 children aged 8 to 17 in the three ecological zones of Ghana. Binary logistic regression was used to examine the predictors of gambling participation while the qualitative data was analysed thematically.

Results

Overall, 3.1% of children aged 8 to 17 had ever engaged in gambling activities. Also, being a female (AOR = 0.210, Wald test = 34.413, 95% CI: 0.125–0.354), having attained primary education (AOR = 4.089, Wald test = 18.643, 95% CI: 2.158–7.749), doing paid work (AOR = 2.536, Wald test = 10.687, 95% CI: 1.452–4.430), having a friend who gambles (AOR = 1.587, Wald test = 4.343; 95% CI: 1.028–2.451), having access to radio (AOR = 1.658, Wald test = 6.694, 95% CI: 1.130–2.431) and having access to mobile phone (AOR = 0.590, Wald test = 6.737, 95% CI: 0.396–0.879) were predictors of gambling participation. Gambling is perceived as harmful by children since it is addictive, affects learning and class attendance, and makes them steal from their families to gamble.

Conclusions

This study demonstrated that socio-demographic characteristics (sex, age, educational attainment, ecological zone, persons taking care of children, living arrangement, engagement in paid work, radio access, mobile phone access) and gambling-related information (having friends who gamble) make children more susceptible to gambling. Researchers and policymakers should consider these socio-demographic characteristics and gambling-related information when designing interventions to curb gambling among children aged 8 to 17 in Ghana.
Augmented reality-assisted systematic mapping of anterolateral thigh perforators
Authors: Tang Yifu , Guo Qiang , Li Xiaoning , Huang Yuzhao , Kuang Wei , Luo Ling
Published: December 2022

Purpose

In soft tissue reconstructive surgery, perforator localization and flap harvesting have always been critical challenges, but augmented reality (AR) has become a dominant technology to help map perforators.

Methods

The lateral circumflex femoral artery (LCFA) and its perforators were reconstructed by CTA in consecutive patients (N = 14). Then, the anterolateral thigh perforators and the points from which the perforators emerged from the deep fascia were marked and projected onto the skin surface. As the virtual images were projected onto patients according to bony markers, the courses of the LCFA and its perforators were depicted on the skin surface for intraoperative guidance. Finally, the locations of the emergence points were verified by intraoperative findings and compared to those determined by handheld Doppler ultrasound.

Results

The sources, locations, and numbers of perforators were determined by CTA. The perforators and their emergence points were accurately mapped on the skin surface by a portable projector to harvest the anterolateral thigh perforator flap. During the operation, the accuracy of the CTA & AR method was 90.2% (37/41), and the sensitivity reached 97.4% (37/38), which were much higher than the corresponding values of Doppler ultrasound. Additionally, the differences between the AR-marked points and the intraoperative findings were much smaller than those seen with Doppler ultrasound (P < 0.001). Consequently, all of the flaps were well designed and survived, and only one complication occurred.

Conclusion

Augmented reality, namely, CTA combined with projection in this study, plays a vital and reliable role in locating the perforator emergence points and guiding the procedure to harvest flaps and has fewer potential risks.
An elderly patient with 17α-hydroxylase deficiency misdiagnosed as primary aldosteronism: a case report
Authors: Ishinoda Yuki , Uto Asuka , Yamada Yoshifumi , Okazaki Maki , Asada Hidetomo , Wakamatsu Seina , Kurihara Isao , Shibata Hironori , Ishii Tomohiro , Hasegawa Tomonobu , Kumagai Hiroo , Kasuga Akira
Published: December 2022

Background

17α-hydroxylase deficiency (17OHD) is a rare autosomal recessive disorder. Aldosterone levels are usually low in patients with 17OHD. However, among the approximately 150 cases of 17OHD reported to date, aldosterone levels were not low in all cases. Therefore, some 17OHD cases may have been misdiagnosed as primary aldosteronism (PA) cases. Often before puberty, 17OHD is diagnosed because of abnormal genital morphology and menstrual irregularities. However, we report a very rare case of 17OHD in an elderly patient with a high aldosterone/renin ratio (ARR) similar to that in PA.

Case presentation

A 63-year-old Japanese woman was transferred to our medical facility for the evaluation of bilateral adrenal hypertrophy, which was incidentally discovered during an abdominal examination after cholecystectomy. The patient had hypokalemia and a high aldosterone/renin ratio. Her medical history included hypertension and right intracerebral capsular hemorrhage at the age of 30 years. Additional testing revealed low cortisol, high adrenocorticotropic hormone, and low testosterone and dehydroepiandrosterone sulfate, indicating congenital adrenal hyperplasia. Genetic analysis revealed a mutation in the CYP17A1 gene and a karyotype of 46, XY; hence, she was diagnosed with 17OHD.

Conclusion

17OHD can resemble PA. The combination of a high ARR and low cortisol level should trigger the consideration of 17OHD.
Presuppositions, cost–benefit, collaboration, and competency impacts palliative care referral in paediatric oncology: a qualitative study
Authors: Salins Naveen , Hughes Sean , Preston Nancy
Published: December 2022

Background

Although a significant proportion of children with cancer need palliative care, few are referred or referred late, with oncologists and haematologists gatekeeping the referral process. We aimed to explore the facilitators and barriers to palliative care referral.

Methods

Twenty-two paediatric oncologists and haematologists were purposively recruited and interviewed. Data were analysed using reflexive thematic analysis. Findings were interpreted using the critical realist paradigm.

Results

Four themes were generated. 1) Oncologists expressed concern about the competency of palliative care teams. Palliative care often symbolised therapeutic failure and abandonment, which hindered referral. Trustworthy palliative care providers had clinical competence, benevolence, and knowledge of oncology and paediatrics. 2) Making a palliative care referral was associated with stigma, navigating illness-related factors, negative family attitudes and limited resources, impeding palliative care referral. 3) There were benefits to palliative care referral, including symptom management and psychosocial support for patients. However, some could see interactions with the palliative care team as interference hindering future referrals. 4) Suggested strategies for developing an integrated palliative care model include evident collaboration between oncology and palliative care, early referral, rebranding palliative care as symptom control and an accessible, knowledgeable, and proactive palliative care team.

Conclusion

Presuppositions about palliative care, the task of making a referral, and its cost-benefits influenced referral behaviour. Early association with an efficient rebranded palliative care team might enhance integration.
Relationships between biological age, distance from aquatic habitats and pyrethroid resistance status of Anopheles funestus mosquitoes in south-eastern Tanzania
Authors: Pinda Polius G. , Msaky Dickson S. , Muyaga Letus L. , Mshani Issa H. , Njalambaha Rukiyah M. , Kihonda Japhet , Bwanaly Hamis , Ngowo Halfan S. , Kaindoa Emmanuel W. , Koekemoer Lizette L. , Okumu Fredros O.
Published: December 2022

Background

Malaria transmission can be highly heterogeneous between and within localities, and is influenced by factors such as survival and biting frequencies of Anopheles mosquitoes. This study investigated the relationships between the biological age, distance from aquatic habitats and pyrethroid resistance status of Anopheles funestus mosquitoes, which currently dominate malaria transmission in south-east Tanzania. The study also examined how such relationships may influence malaria transmission and control.

Methods

Female An. funestus were collected in houses located 50–100 m, 150–200 m or over 200 m from the nearest known aquatic habitats. The mosquitoes were exposed to 1×, 5× and 10× the diagnostic doses of deltamethrin or permethrin, or to the synergist, piperonyl butoxide (PBO) followed by the pyrethroids, then monitored for 24 h-mortality. Ovaries of exposed and non-exposed mosquitoes were dissected to assess parity as a proxy for biological age. Adults emerging from larval collections in the same villages were tested against the same insecticides at 3–5, 8–11 or 17–20 days old.

Findings

Mosquitoes collected nearest to the aquatic habitats (50-100 m) had the lowest mortalities compared to other distances, with a maximum of 51% mortality at 10× permethrin. For the age-synchronized mosquitoes collected as larvae, the insecticide-induced mortality assessed at both the diagnostic and multiplicative doses (1×, 5× and 10×) increased with mosquito age. The highest mortalities at 1× doses were observed among the oldest mosquitoes (17–20 days). At 10× doses, mortalities were 99% (permethrin) and 76% (deltamethrin) among 8–11 day-olds compared to 80% (permethrin) and 58% (deltamethrin) among 3–5 day-olds. Pre-exposure to PBO increased the potency of both pyrethroids. The proportion of parous females was highest among mosquitoes collected farthest from the habitats.

Conclusion

In this specific setting, older An. funestus and those collected farthest from the aquatic habitats (near the centre of the village) were more susceptible to pyrethroids than the younger ones and those caught nearest to the habitats. These findings suggest that pyrethroid-based interventions may remain at least moderately effective despite widespread pyrethroid-resistance, by killing the older, less-resistant and potentially-infective mosquitoes. Further studies should investigate how and whether these observations could be exploited to optimize malaria control in different settings.
18F-FET PET radiomics-based survival prediction in glioblastoma patients receiving radio(chemo)therapy
Authors: Wiltgen Tun , Fleischmann Daniel F. , Kaiser Lena , Holzgreve Adrien , Corradini Stefanie , Landry Guillaume , Ingrisch Michael , Popp Ilinca , Grosu Anca L. , Unterrainer Marcus , Bartenstein Peter , Parodi Katia , Belka Claus , Albert Nathalie , Niyazi Maximilian , Riboldi Marco
Published: December 2022

Background

Quantitative image analysis based on radiomic feature extraction is an emerging field for survival prediction in oncological patients. 18F-Fluorethyltyrosine positron emission tomography (18F-FET PET) provides important diagnostic and grading information for brain tumors, but data on its use in survival prediction is scarce. In this study, we aim at investigating survival prediction based on multiple radiomic features in glioblastoma patients undergoing radio(chemo)therapy.

Methods

A dataset of 37 patients with glioblastoma (WHO grade 4) receiving radio(chemo)therapy was analyzed. Radiomic features were extracted from pre-treatment 18F-FET PET images, following intensity rebinning with a fixed bin width. Principal component analysis (PCA) was applied for variable selection, aiming at the identification of the most relevant features in survival prediction. Random forest classification and prediction algorithms were optimized on an initial set of 25 patients. Testing of the implemented algorithms was carried out in different scenarios, which included additional 12 patients whose images were acquired with a different scanner to check the reproducibility in prediction results.

Results

First order intensity variations and shape features were predominant in the selection of most important radiomic signatures for survival prediction in the available dataset. The major axis length of the 18F-FET-PET volume at tumor to background ratio (TBR) 1.4 and 1.6 correlated significantly with reduced probability of survival. Additional radiomic features were identified as potential survival predictors in the PTV region, showing 76% accuracy in independent testing for both classification and regression.

Conclusions

18F-FET PET prior to radiation provides relevant information for survival prediction in glioblastoma patients. Based on our preliminary analysis, radiomic features in the PTV can be considered a robust dataset for survival prediction.
The effectiveness of using virtual reality technology for perioperative anxiety among adults undergoing elective surgery: a randomised controlled trial protocol
Authors: Asiri Salihah , Guilhermino Michelle , Duff Jed
Published: December 2022

Background

More than 2.5 million people are admitted for surgery in Australia each year, and between 40 to 80% will experience moderate to high preoperative anxiety. Elevated levels of preoperative anxiety can increase the risk of postoperative complications such as pain, delayed wound healing, infection, prolonged recovery, and longer hospitalisation. Limited previous research on Virtual Reality (VR) indicates a positive impact on surgery-related anxiety and suggests that the intervention potentially leads to reduce postoperative complications.

Objective

To evaluate the effectiveness of using VR technology for perioperative anxiety among adults undergoing elective surgery.

Method

A two-group parallel randomised controlled trial (RCT) will be conducted, including 150 adult patients (aged 18 years and over) undergoing elective surgery and requiring an overnight stay at a major metropolitan hospital. Eligible participants will be screened for anxiety via the Amsterdam Preoperative Anxiety and Information score (APAIS). Those with moderate to severe anxiety will be randomly allocated to receive the VR session or usual care, in the preoperative holding area. Intervention participants will use a head-mounted VR device to watch and listen to a nature scene for 10 minutes.

Study outcomes

The primary outcome is perioperative anxiety measured using the visual analogue scale for anxiety (VAS-A). Secondary outcomes include stress levels (measured by saliva cortisol level and heart rate), postoperative pain, patient satisfaction with perioperative care, hospital length of stay, and VR-associated adverse events.

Conclusion

This study will help evaluate if a brief preoperative VR session can reduce perioperative anxiety for adult elective surgical patients.

Trial registration

Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620001350910.
Treatment of pregnant and early postpartum women with severe and critical COVID-19: experience at a tertiary center
Authors: Barbosa Rodrigo Nacif , Braga Maria Aparecida , Costa Bárbara Braga , Peret Frederico José Amedee
Published: December 2022

Background

The management of acute respiratory failure during pregnancy is a poorly defined issue in the literature, especially regarding the use of the prone position and the appropriate time for delivery. This study describes our experience in treating pregnant and postpartum women with severe or critical coronavirus disease 2019 (COVID-19).

Materials and methods

This descriptive retrospective study included 25 pregnant and 4 postpartum women admitted to an ICU due to respiratory complications from COVID-19 from June 2020 to August 2021.

Results

The mean maternal age was 33.6 years, and the median gestational age (GA) at admission was 33 weeks. Obesity was the most common comorbidity. The median time between symptom onset and ICU admission was 10 days, while the median length of ICU stay was 14 days. Invasive mechanical ventilation (IMV) was required in 16 (55.2%) patients for a median time of 16.5 days. Prone positioning (PP) was performed in 68.7% of the patients on IMV, and resulted in an expressive increase in arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio). Eleven (44%) pregnant women delivered during their ICU stay for obstetric or fetal reasons: of these, 2 (18%) developed postpartum hemorrhagic shock and 1 (9%) developed abdominal wall infection. None of the 25 pregnant women underwent delivery due to acute respiratory failure or in an attempt to avoid intubation. There were 2 fetal deaths, but no maternal or neonatal deaths.

Conclusion

We observed favorable outcomes in pregnant and postpartum women with severe and critical COVID-19 admitted to our institution. This finding reinforces the effectiveness of PP in the treatment of hypoxemic respiratory failure secondary to COVID-19 in pregnant women undergoing IMV, and suggests that gestation should only be interrupted in cases of obstetric and fetal complications, provided the patient is stable, or when hypoxemia is refractory to PP.
Exposure assessment and risk characterization of aflatoxins intake through consumption of maize (Zea mays) in different age populations in the Volta Region of Ghana
Authors: Kortei Nii Korley , Annan Theophilus , Dzikunoo John , Agbetiameh Daniel
Published: December 2022

Aflatoxin contamination in foods is a vital health challenge for low and middle-income countries in subtropical regions. Maize (Zea mays L.), a staple food most widely grown in Africa including Ghana, and extensively consumed as much as three times per day, is a source of aflatoxin contamination owing to its susceptibility to fungal infection. Aflatoxin levels were checked against international (European Commission, EC) and local (Ghana Standards Authority, GSA) standards, and health risks associated with maize sampled from the Volta Region (Hohoe, Ho, Battor Dugame, and Keta) of Ghana were determined. Total aflatoxins (totalAFs) and the constituent aflatoxins (AFB1, AFB2, AFG1, and AFG2) were measured with High-Performance Liquid Chromatography (HPLC) with a Fluorescence Detector (FLD). Intake and Risk assessments were also conducted using deterministic models prescribed by the Joint FAO/WHO Expert Committee on Additives (JECFA). The degree of occurrence of aflatoxins was observed to be in decreasing order of AFG2 < AFG1 < AFB2 < AFB1 and were within the ranges of 0.78 ± 0.04 $$-$$
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234.73 ± 3.8 µg/kg, 0.47 ± 0.03 $$-$$
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21.6 ± 0.33 µg/kg, 1.01 ± 0.05 $$-$$
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13.75 ± 1.2 µg/kg and 0.66 ± 0.06 $$-$$
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5.51 ± 0.26 µg/kg respectively. Out of the 100 samples analyzed for total aflatoxins (totalAFs), 68 (68%) exceeded the limits of EC and were of range 4.98 ± 0.6 $$-$$
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445.01 ± 8.9 µg/kg whereas 58 (58%) and ranged between 12.12 ± 1.4 $$-$$
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445.01 ± 8.9 µg/kg exceeded GSA limits. Intake and risk assessments of total aflatoxins (totalAFs) for infants, toddlers, children, adolescents, and adults in the Volta Region were; 0.037–1.14 µg/kg bw/day, 0.35–10.81, and 1.47 -45.14 cases/10,000 person/yr respectively for Estimated Daily Intake (EDI), Margin of Exposure (MOE), and Cancer Risks. It was inferred that the consumption of maize posed potential adverse health effects on all age categories studied because all calculated MOE values were less than 10,000.
The Resistance Exercise in Already Active Diabetic Individuals (READI) Randomized Clinical Trial
Authors: Sigal Ronald J , Yardley Jane E , Perkins Bruce A , Riddell Michael C , Goldfield Gary S , Donovan Lois , Malcolm Janine , Hadjiyannakis Stasia , Edwards Alun L , Gougeon Réjeanne , Wells George A , Pacaud Danièle , Woo Vincent , Ford Gordon T , Coyle Doug , Phillips Penny , Doucette Steve , Khandwala Farah , Kenny Glen P ,   the READI Trial Investigators, Phillips Penny , Mitchell Diana , Richardson Janet , Gilchrist Colleen , Rouatt Sharon , Orszag Andrej , Baughan Lynn , Clearwaters Mary Ann , Ilnyckyj Maria , Pockett Sheri , Berard Lori , Hind Krista , Wein Marta , Robertson Kimberly , Phillips Kelley , Hanlon Brittany , Santilli Antonio , Potter Dave , Jarvis Chris , Jarvie Ian , Petrie Alison , Ori Elaine , Wood Blake , Despielgelaere Marc , Murphy Ann , Gillam Melanie , Zarn Dayna , Janzen Laela
Published: December 2022

Context

Resistance exercise training (strength training) and aerobic exercise training are both recommended for people with type 1 diabetes, but it is unknown whether adding resistance exercise provides incremental benefits in people with this condition who already perform aerobic exercise regularly.

Objective

This work aimed to evaluate the incremental effect of resistance training on glycated hemoglobin A1c (HbA1c), fitness, body composition, and cardiometabolic risk factors in aerobically active people with type 1 diabetes.

Methods

The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a 4-center, randomized, parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically active individuals with type 1 diabetes were randomly assigned to resistance exercise (n = 71, intervention—INT) or control (n = 60, CON) for 22 additional weeks. Both groups maintained their aerobic activities and were provided dietary counseling throughout. Exercise training was 3 times per week at community-based facilities. The primary outcome was HbA1c, and secondary outcomes included fitness (peak oxygen consumption, muscle strength), body composition (anthropometrics, dual-energy x-ray absorptiometry, computed tomography), and cardiometabolic risk markers (lipids, apolipoproteins). Assessors were blinded to group allocation.

Results

There were no significant differences in HbA1c change between INT and CON. Declines in HbA1c (INT: 7.75 ± 0.10% [61.2 ± 1.1 mmol/mol] to 7.55 ± 0.10% [59 ± 1.1 mmol/mol]; CON: 7.70 ± 0.11% [60.7 ± 1.2 mmol/mol] to 7.57 ± 0.11% [59.6 ± 1.3 mmol/mol]; intergroup difference in change −0.07 [95% CI, −0.31 to 0.18]). Waist circumference decreased more in INT than CON after 6 months (P = .02). Muscular strength increased more in INT than in CON (P < .001). There were no intergroup differences in hypoglycemia or any other variables.

Conclusion

Adding resistance training did not affect glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.
Glucagon-like Peptide-2 Acutely Enhances Chylomicron Secretion in Humans Without Mobilizing Cytoplasmic Lipid Droplets
Authors: Syed-Abdul Majid Mufaqam , Stahel Priska , Zembroski Alyssa , Tian Lili , Xiao Changting , Nahmias Avital , Bookman Ian , Buhman Kimberly K , Lewis Gary F
Published: December 2022

Context

A portion of ingested fats are retained in the intestine for many hours before they are mobilized and secreted in chylomicron (CM) particles. Factors such as glucagon-like peptide-2 (GLP-2) and glucose can mobilize these stored intestinal lipids and enhance CM secretion. We have recently demonstrated in rodents that GLP-2 acutely enhances CM secretion by mechanisms that do not involve the canonical CM synthetic assembly and secretory pathways.

Objective

To further investigate the mechanism of GLP-2's potent intestinal lipid mobilizing effect, we examined intracellular cytoplasmic lipid droplets (CLDs) in intestinal biopsies of humans administered GLP-2 or placebo.

Design, setting, patients, and interventions

A single dose of placebo or GLP-2 was administered subcutaneously 5 hours after ingesting a high-fat bolus. In 1 subset of participants, plasma samples were collected to quantify lipid and lipoprotein concentrations for 3 hours after placebo or GLP-2. In another subset, a duodenal biopsy was obtained 1-hour after placebo or GLP-2 administration for transmission electron microscopy and proteomic analysis.

Results

GLP-2 significantly increased plasma triglycerides by 46% (P = 0.009), mainly in CM-sized particles by 133% (P = 0.003), without reducing duodenal CLD size or number. Several proteins of interest were identified that require further investigation to elucidate their potential role in GLP-2-mediated CM secretion.

Conclusions

Unlike glucose that mobilizes enterocyte CLDs and enhances CM secretion, GLP-2 acutely increased plasma CMs without significant mobilization of CLDs, supporting our previous findings that GLP-2 does not act directly on enterocytes to enhance CM secretion and most likely mobilizes secreted CMs in the lamina propria and lymphatics.
Impact of the Complexity of Glucose Time Series on All-Cause Mortality in Patients With Type 2 Diabetes
Authors: Cai Jinghao , Yang Qing , Lu Jingyi , Shen Yun , Wang Chunfang , Chen Lei , Zhang Lei , Lu Wei , Zhu Wei , Xia Tian , Zhou Jian
Published: December 2022

Context

Previous studies suggest that the complexity of glucose time series may serve as a novel marker of glucose homeostasis.

Objective

We aimed to investigate the relationship between the complexity of glucose time series and all-cause mortality in patients with type 2 diabetes.

Methods

Prospective data of 6000 adult inpatients with type 2 diabetes from a single center were analyzed. The complexity of glucose time series index (CGI) based on continuous glucose monitoring (CGM) was measured at baseline with refined composite multiscale entropy. Participants were stratified by CGI tertiles of: < 2.15, 2.15 to 2.99, and ≥ 3.00. Cox proportional hazards regression models were used to assess the relationship between CGI and all-cause mortality.

Results

During a median follow-up of 9.4 years, 1217 deaths were identified. A significant interaction between glycated hemoglobin A1c (HbA1c) and CGI in relation to all-cause mortality was noted (P for interaction = 0.016). The multivariable-adjusted hazard ratios for all-cause mortality at different CGI levels (≥ 3.00 [reference group], 2.15-2.99, and < 2.15) were 1.00, 0.76 (95% CI, 0.52-1.12), and 1.47 (95% CI, 1.03-2.09) in patients with HbA1c < 7.0%, while the association was nonsignificant in those with HbA1c ≥ 7.0%. The restricted cubic spline regression revealed a nonlinear (P for nonlinearity = 0.041) relationship between CGI and all-cause mortality in subjects with HbA1c < 7.0% only.

Conclusion

Lower CGI is associated with an increased risk of all-cause mortality among patients with type 2 diabetes achieving the HbA1c target. CGI may be a new indicator for the identification of residual risk of death in well-controlled type 2 diabetes.
Association of Longitudinal Activity Measures and Diabetes Risk: An Analysis From the National Institutes of Health All of Us Research Program
Authors: Perry Andrew S , Annis Jeffrey S , Master Hiral , Nayor Matthew , Hughes Andrew , Kouame Aymone , Natarajan Karthik , Marginean Kayla , Murthy Venkatesh , Roden Dan M , Harris Paul A , Shah Ravi , Brittain Evan L
Published: December 2022

Context

Prior studies of the relationship between physical activity and incident type 2 diabetes mellitus (T2DM) relied primarily on questionnaires at a single time point.

Objective

We sought to investigate the relationship between physical activity and incident T2DM with an innovative approach using data from commercial wearable devices linked to electronic health records in a real-world population.

Methods

Using All of Us participants’ accelerometer data from their personal Fitbit devices, we used a time-varying Cox proportional hazards models with repeated measures of physical activity for the outcome of incident T2DM. We evaluated for effect modification with age, sex, body mass index (BMI), and sedentary time using multiplicative interaction terms.

Results

From 5677 participants in the All of Us Research Program (median age 51 years; 74% female; 89% White), there were 97 (2%) cases of incident T2DM over a median follow-up period of 3.8 years between 2010 to 2021. In models adjusted for age, sex, and race, the hazard of incident diabetes was reduced by 44% (95% CI, 15%-63%; P = 0.01) when comparing those with an average daily step count of 10 700 to those with 6000. Similar benefits were seen comparing groups based on average duration of various intensities of activity (eg, lightly active, fairly active, very active). There was no evidence for effect modification by age, sex, BMI, or sedentary time.

Conclusion

Greater time in any type of physical activity intensity was associated with lower risk of T2DM irrespective of age, sex, BMI, or sedentary time.
Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans
Authors: Sommer Christine , Vangberg Kjersti G , Moen Gunn-Helen , Evans David M , Lee-Ødegård Sindre , Blom-Høgestøl Ingvild K , Sletner Line , Jenum Anne K , Drevon Christian A , Gulseth Hanne L , Birkeland Kåre I
Published: December 2022

Context

Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown.

Objective

This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity.

Methods

We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization.

Results

In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (β [95% CI] −0.19 [−0.21 to −0.17]), body fat (−0.12 [−0.14 to −0.10), and fasting C-peptide (−2.04 [−2.46 to −1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (−0.5 [−0.7 to −0.4] and −0.5 [−0.6 to −0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, −1.72 [−2.86 to −0.58], and −0.20 [−0.36 to −0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R.

Conclusion

BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling.
Selective refinement of glutamate and GABA synapses on dorsal raphe 5-HT neurons during postnatal life
Authors: Argañaraz Carla V. , Adjimann Tamara S. , Perissinotti Paula P. , Soiza-Reilly Mariano
Published: December 2022

Serotonin (5-hydroxytryptamine, 5-HT) neurons are implicated in the etiology and therapeutics of anxiety and depression. Critical periods of vulnerability during brain development enable maladaptive mechanisms to produce detrimental consequences on adult mood and emotional responses. 5-HT plays a crucial role in these mechanisms; however, little is known about how synaptic inputs and modulatory systems that shape the activity of early 5-HT networks mature during postnatal development. We investigated in mice the postnatal trajectory of glutamate and GABA synaptic inputs to dorsal raphe nucleus (DRN) 5-HT neurons, the main source of forebrain 5-HT. High-resolution quantitative analyses with array tomography and ex vivo electrophysiology indicate that cortical glutamate and subcortical GABA synapses undergo a profound refinement process after the third postnatal week, whereas subcortical glutamate inputs do not. This refinement of DRN inputs is not accompanied by changes in 5-HT1A receptor-mediated inhibition over 5-HT neurons. Our study reveals a precise developmental pattern of synaptic refinement of DRN excitatory and inhibitory afferents, when 5-HT-related inhibitory mechanisms are in place. These findings contribute to the understanding of neurodevelopmental vulnerability to psychiatric disorders.

This article has an associated ‘The people behind the papers’ interview.
Hammerhead ribozyme-based U-insertion and deletion RNA editing assays for multiplexing in HTS applications
Authors: Rostamighadi Mojtaba , Mehta Vaibhav , Hassan Khan Rufaida , Moses Daniel , Salavati Reza
Published: December 2022

Untranslatable mitochondrial transcripts in kinetoplastids are decrypted post-transcriptionally through an RNA editing process that entails uridine insertion/deletion. This unique stepwise process is mediated by the editosome, a multiprotein complex that is a validated drug target of considerable interest in addressing the unmet medical needs for kinetoplastid diseases. With that objective, several in vitro RNA editing assays have been developed, albeit with limited success in discovering potent inhibitors. This manuscript describes the development of three hammerhead ribozyme (HHR) FRET reporter-based RNA editing assays for precleaved deletion, insertion, and ligation assays that bypass the rate-limiting endonucleolytic cleavage step, providing information on U-deletion, U-insertion, and ligation activities. These assays exhibit higher editing efficiencies in shorter incubation times while requiring significantly less purified editosome and 10,000-fold less ATP than the previously published full round of in vitro RNA editing assay. Moreover, modifications in the reporter ribozyme sequence enable the feasibility of multiplexing a ribozyme-based insertion/deletion editing (RIDE) assay that simultaneously surveils U-insertion and deletion editing suitable for HTS. These assays can be used to find novel chemical compounds with chemotherapeutic applications or as probes for studying the editosome machinery.
Η φοροδιαφυγή στην Ελλάδα
Authors: Καλαμαρά Ελένη
Published: December 2022

Σκοπός της μελέτης αυτής αποτελεί η εκτίμηση του μεγέθους της φοροδιαφυγής στην Ελλάδα για την περίοδο 1980-2018. Για την εκτίμηση αυτή επιλέχθηκε η εφαρμογή έμμεσης μεθόδου προσέγγισης του ζητήματος, όπως αυτή αναπτύχθηκε από τον Tanzi και στηρίζεται στην υπόθεση ότι η εκτίμηση του μεγέθους της παραοικονομίας μπορεί να μας οδηγήσει σε μια ασφαλή μέτρηση του μεγέθους της φοροδιαφυγής. Ειδικότερα, μέσω της προσέγγισης της Ζήτησης Ρευστών Διαθεσίμων η οποία στηρίζεται στη βασική υπόθεση ότι οι δραστηριότητες που εντάσσονται στο πλαίσιο της σκιώδους οικονομίας αποτελούν την άμεση αντίδραση των φορολογουμένων στην αυξημένη φορολογική επιβάρυνση και ότι τα μετρητά χρησιμοποιούνται κυρίως για τη διεξαγωγή τέτοιων συναλλαγών και την συγκέντρωση του πλούτου που προέρχεται από αυτές, προσδιορίστηκε το μέγεθος της παραοικονομίας κάνοντας χρήση της μεθόδου της ερευνητικής ομάδας του Πανεπιστημίου του Leicester και στη συνέχεια εκτιμήθηκε το επίπεδο της φοροδιαφυγής επιβάλλοντας σε αυτό ένα ετήσιο φορολογικό συντελεστή, ως το λόγο των συνολικών φορολογικών εσόδων προς την Ακαθάριστη Προστιθέμενη Αξία. Τα αποτελέσματα έδειξαν μια σημαντική αύξηση του μεγέθους της φοροδιαφυγής κατά την υπό εξέταση περίοδο, ενώ από την εκτίμηση του υποδείγματος προέκυψε ότι το μεγαλύτερο μέρος της φοροδιαφυγής προέρχεται από την άμεση φορολογία. Επιπρόσθετα, αντικείμενο της έρευνας αποτελεί η ανακάλυψη των αιτιωδών σχέσεων μεταξύ του επιπέδου φοροδιαφυγής στην Ελλάδα και ενός συνόλου πιθανών προσδιοριστικών παραγόντων της, χρησιμοποιώντας κατάλληλες οικονομετρικές μεθόδους ανάλυσης χρονολογικών σειρών. Συγκεκριμένα, μέσω της μεθόδου συνολοκλήρωσης και την εκτίμηση Υποδειγμάτων Διόρθωσης Σφάλματος, επιχειρείται η ανακάλυψη των σχέσεων αιτιότητας και του βαθμού αλληλεξάρτησης μεταξύ του μεγέθους της φοροδιαφυγής και ενός συνόλου παραγόντων. Τα αποτελέσματα της ανάλυσης υποδεικνύουν ένα σημαντικό βαθμό αλληλεξαρτήσεων, στοιχείο που αποτελεί σημαντικό εργαλείο άσκησης στοχευμένης και αποτελεσματικής πολιτικής καταπολέμησης της φοροδιαφυγής. Συγκεκριμένα, η έρευνα έδειξε ότι το επίπεδο των φορολογικών συντελεστών, το επίπεδο της ανεργίας, ο δείκτης Rule of Laws, το επίπεδο του Α.Ε.Π., το επίπεδο των μη εξυπηρετούμενων δανείων, η κυβερνητική αποτελεσματικότητα, ο δείκτης αντίληψης διαφθοράς και το επίπεδο της τελικής καταναλωτικής δαπάνης επηρεάζουν σημαντικά το μέγεθος της φοροδιαφυγής στην Ελλάδα. Περαιτέρω, πραγματοποιείται ανάλυση αποσύνθεσης διακύμανσης και συναρτήσεων αιφνιδίων αντιδράσεων, τα αποτελέσματα των οποίων υποστηρίζουν τα παραπάνω ευρήματα, παρέχοντας ταυτόχρονα μια ποσοτική απεικόνιση των αιτιωδών σχέσεων μεταξύ των υπό διερεύνηση παραγόντων και της φοροδιαφυγής.
Exploitation of Greek flora for the discovery of antioxidant and skin-whitening natural compounds based on HPTLC and CPC techniques
Authors: Μπόκα Βασιλική-Ιωάννα
Published: December 2022

Η χρήση των φυτών ως φαρμάκων προηγείται της γραπτής ανθρώπινης ιστορίας. Πολλά από τα βότανα και τα μπαχαρικά που χρησιμοποιούνται από τους ανθρώπους για να καρυκεύσουν τα τρόφιμα παρέχουν επίσης χρήσιμες φαρμακευτικές ενώσεις. Σήμερα, η χρήση βοτάνων για τη θεραπεία ασθενειών είναι σχεδόν καθολική στις μη βιομηχανοποιημένες κοινωνίες και η αναζήτηση φαρμάκων και συμπληρωμάτων διατροφής που προέρχονται από φυτά έχει επιταχυνθεί. Εξάλλου, στη σύγχρονη κοινωνία, υπάρχει μεγάλη αύξηση στις έρευνες σχετικά με τη γήρανση και την αναγκαιότητα εύρεσης τρόπων πρόληψης ή αναστολής της. Ειδικά, όσον αφορά τα αντιοξειδωτικά και τους λευκαντικούς παράγοντες στη φροντίδα του δέρματος, τα προϊόντα μπορούν πλέον να θεωρηθούν ενεργά και ωφέλιμα καθώς περιέχουν «βιοδραστικές ουσίες» που αν και δεν είναι φαρμακευτικές, παρέχουν ποικίλες λειτουργικές ιδιότητες. Η ελληνική χλωρίδα είναι μια εξαιρετική πηγή φυσικών «βιοδραστικών», καθώς αποτελείται από περίπου 6700 είδη εκ των οποίων περίπου το 22% είναι ενδημικά. Παρ' όλα αυτά, μόνο ένα μικρό ποσοστό, περίπου το 10%, των ταξινομημένων φυτών έχει διερευνηθεί και χαρακτηριστεί χημικά. Το ζήτημα που προκύπτει με την ύπαρξη τέτοιων αριθμών είναι πώς να αποφευχθεί η επίπονη και χρονοβόρα απομόνωση μεμονωμένων ενώσεων.Η οικογένεια Lamiaceae διερευνήθηκε ως προς την αντιοξειδωτική της ικανότητα, με στόχο τον εντοπισμό και την άμεση ανακάλυψη κύριων δραστικών δευτερογενών μεταβολιτών. Εφαρμόστηκαν απλές και γρήγορες αναλύσεις για την υποστήριξη μιας διαδικασίας υψηλής απόδοσης βασίσμένη στις τεχνικές της HPTLC και FCPC. Εκατόν ογδόντα φυτικά (180) εκχυλίσματα ερευνήθηκαν για την αντιοξειδωτική τους ικανότητα οδηγώντας μας σε έντεκα (11) τελικά εκχυλίσματα. Τα 11 είδη και υποείδη αξιολογήθηκαν περαιτέρω (ABTS, ROS), ενώ οι κύριες ενώσεις κάθε εκχυλίσματος ανιχνεύθηκαν μέσω HPTLC-αυτογραφίας. Περαιτέρω, καθιερώθηκαν δύο διαδικασίες που θα μας οδηγούσαν σε σύντομο χρονικό διάστημα στην επιλογή ενός μικρού αριθμού κατάλληλων διφασικών συστημάτων διαλυτών για τη διαδικασία FCPC καταλήγοντας στην απομόνωση των δευτερογενών μεταβολιτών με ισχυρή αντιοξειδωτική ικανότητα.Για την ανακάλυψη φυσικών προϊόντων με ιδιότητες λεύκανσης του δέρματος από ελληνικά φυτικά εκχυλίσματα, έγινε μια προσπάθεια συνδυασμού τριών τεχνικών High-Throughput Screening (HTS) (προσέγγιση NMR-Heterocvariance, HPTLC-Based Activity Profiles and HPTLC-autography) για τη δημιουργία ενός ολοκληρωμένης πολυμεταβλητής στατιστικής πλατφόρμας. Οκτώ εκχυλίσματα που προέρχονται από φυτά της ελληνικής χλωρίδας (Armeria canescens, Cercis siliquastrum, Pistacia terebinthus, Paeonia mascula ssp hellenica, Paeonia clusii ssp. clusii, Veratrum άλμπουμ, Cistus salvifolius και Sedum sediforme επιλέχθηκαν με στατιστικά στοιχεία high-investment and sediforme) επιλέχθηκαν και διευρευνήθηκαν μέσω της πλατφόρμας αυτής για τον εντοπισμό και την ταυτοποίηση των φυσικών ενώσεων με λευκαντική δράση χωρίς την ανάγκη της απομόνωσής τους.
Μελέτη του γονιδίου C9ORF72 σε Έλληνες ασθενείς με νευροεκφυλιστικά νοσήματα
Authors: Καρτάνου Χρυσούλα
Published: December 2022

Η επέκταση του γονιδίου C9ORF72 αποτελεί γενετική αιτία της πλαγίας μυατροφικής σκλήρυνσης (ALS) και της μετωποκροταφικής άνοιας (FTD), ενώ συμμετέχει στην αιτιοπαθογένεια και των συνδρόμων Huntington-like (HD-like), της νόσου Parkinson (PD) και της νόσου Alzheimer (AD). Σκοπός της παρούσας μελέτης είναι ο φαινοτυπικός και γονοτυπικός χαρακτηρισμός νοσημάτων που σχετίζονται με το γονίδιο C9ORF72 στην Ελλάδα. 957 ασθενείς (467 με ALS, 53 με σύνδρομα HD-like, 247 με άνοια, 175 με PD και 15 με κληρονομική σπαστική παραπληγία, (HSP) και 93 μάρτυρες ελέγχθηκαν για τη μεταλλαγή. Σαράντα εννιά ασθενείς με ALS (10,5%), 2 με σύνδρομα HD-like (3,8%), 13 με FTD (11,5%), 1 με AD (1,6%) και 2 με PD (1,1%) αποδείχθηκαν θετικοί για την επέκταση. Τονίζεται η σημασία του γενετικού ελέγχου για το γονίδιο C9ORF72 σε Έλληνες ασθενείς με οικογενείς και σποραδικές μορφές ALS ή/και FTD και σύνδρομα HD-like.
Κοινωνικοποίηση του παιδιού
Authors: Κολιού Στεργούλα
Published: December 2022

Η παρούσα διδακτορική διατριβή αποσκοπεί αφενός στη διερεύνηση εκείνων των παραγόντων της οικογένειας που διαφοροποιούν τα εκπαιδευτικά χαρακτηριστικά, τις επαγγελματικές προσδοκίες και τα ατομικά χαρακτηριστικά του παιδιού και αφετέρου στον προσδιορισμό του μεγέθους της επίδρασης των παραγόντων αυτών. Βασική διάσταση της παρούσας έρευνας είναι η περιγραφή και διερεύνηση των κοινωνικοοικονομικών και πολιτισμικών παραγόντων της οικογένειας και η επίδρασή τους στη σχολική επίδοση, στα ατομικά χαρακτηριστικά, στις προσδοκίες και στις επιλογές των παιδιών. Επιπλέον, σημαντική θεματική της παρούσας έρευνας είναι η διερεύνηση του ρόλου των νέων τεχνολογιών και μέσων κοινωνικής δικτύωσης και επικοινωνίας, που χαρακτηρίζουν τη σύγχρονη ψηφιακή εποχή, τόσο στην κοινωνικοποίηση του παιδιού, όσο και στα εκπαιδευτικά και ατομικά του χαρακτηριστικά, αλλά και στις προσδοκίες του. Μέσα από τη σύνθεση των παραπάνω δεδομένων και την ανάλυση των αποτελεσμάτων, η παρούσα έρευνα οδήγησε στο συμπέρασμα πως ο θεσμός της οικογένειας εξακολουθεί να διαδραματίζει τον καταλυτικότερο ρόλο στην κοινωνικοποίηση του παιδιού, παρουσιάζοντας επαναπροσδιορισμό των αναγκών και των χαρακτηριστικών του και μια ιδιαίτερη προσαρμοστικότητα κι ευελιξία, εναρμονισμένη με τις ανάγκες και τις αλλαγές που χαρακτηρίζουν τη σύγχρονη εποχή. Σημαντικό παράγοντα και σύγχρονη διάσταση της παρούσας έρευνας αποτέλεσαν οι νέες τεχνολογίες και τα μέσα μαζικής επικοινωνίας και δικτύωσης που χαρακτηρίζουν την εποχή μας και μαζί με τα οικογενειακά χαρακτηριστικά παρατηρήθηκε να επηρεάζουν καταλυτικά ήδη από τις μικρές ηλικίες τις αντιλήψεις και τα εκπαιδευτικά και ατομικά χαρακτηριστικά των παιδιών.