bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoconjugates to enhance PDT-mediated cancer
immunotherapy by targeting the indoleamine-2,3-dioxygenase pathway
Authors: Yang Xueyuan , Zhang Weizhong , Jiang Wen , Kumar Anil , Zhou Shiyi , Cao Zhengwei , Zhan Shuyue , Yang Wei , Liu Rui , Teng Yong , Xie Jin 
Published: June 2021

Abstract
Background
Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored.

Methods
Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF16Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice.

Results
Our results showed that PPF NPs can efficiently encapsulate both ZnF16Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8+ T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor eradication, and they successfully rejected a second tumor inoculation. Overall, our studies introduce a unique composite nanoplatform that allows for co-delivery of photosensitizer and IDO inhibitor with minimal inter-species interference, which is ideal for combination therapy.
Acute cardiovascular effects of controlled exposure to dilute Petrodiesel and biodiesel exhaust in healthy volunteers: a crossover study
Authors: Unosson Jon , Kabéle Mikael , Boman Christoffer , Nyström Robin , Sadiktsis Ioannis , Westerholm Roger , Mudway Ian S. , Purdie Esme , Raftis Jennifer , Miller Mark R. , Mills Nicholas L. , Newby David E. , Blomberg Anders , Sandström Thomas , Bosson Jenny A. 
Published: June 2021

Abstract
Background
Air pollution derived from combustion is associated with considerable cardiorespiratory morbidity and mortality in addition to environmental effects. Replacing petrodiesel with biodiesel may have ecological benefits, but impacts on human health remain unquantified.
The objective was to compare acute cardiovascular effects of blended and pure biodiesel exhaust exposure against known adverse effects of petrodiesel exhaust (PDE) exposure in human subjects.
In two randomized controlled double-blind crossover studies, healthy volunteers were exposed to PDE or biodiesel exhaust for one hour. In study one, 16 subjects were exposed, on separate occasions, to PDE and 30% rapeseed methyl ester biodiesel blend (RME30) exhaust, aiming at PM10 300 μg/m3. In study two, 19 male subjects were separately exposed to PDE and exhaust from a 100% RME fuel (RME100) using similar engine load and exhaust dilution. Generated exhaust was analyzed for physicochemical composition and oxidative potential. Following exposure, vascular endothelial function was assessed using forearm venous occlusion plethysmography and ex vivo thrombus formation was assessed using a Badimon chamber model of acute arterial injury. Biomarkers of inflammation, platelet activation and fibrinolysis were measured in the blood.

Results
In study 1, PDE and RME30 exposures were at comparable PM levels (314 ± 27 μg/m3; (PM10 ± SD) and 309 ± 30 μg/m3 respectively), whereas in study 2, the PDE exposure concentrations remained similar (310 ± 34 μg/m3), but RME100 levels were lower in PM (165 ± 16 μg/m3) and PAHs, but higher in particle number concentration. Compared to PDE, PM from RME had less oxidative potential. Forearm infusion of the vasodilators acetylcholine, bradykinin, sodium nitroprusside and verapamil resulted in dose-dependent increases in blood flow after all exposures. Vasodilatation and ex vivo thrombus formation were similar following exposure to exhaust from petrodiesel and the two biodiesel formulations (RME30 and RME100). There were no significant differences in blood biomarkers or exhaled nitric oxide levels between exposures.

Conclusions
Despite differences in PM composition and particle reactivity, controlled exposure to biodiesel exhaust was associated with similar cardiovascular effects to PDE. We suggest that the potential adverse health effects of biodiesel fuel emissions should be taken into account when evaluating future fuel policies.

Trial registration
ClinicalTrials.gov, NCT01337882/NCT01883466. Date of first enrollment March 11, 2011, registered April 19, 2011, i.e. retrospectively registered.
Breastfeeding and employed mothers in Ethiopia: legal protection, arrangement, and support
Authors: Kebede Ermiyas Mulu , Seifu Benyam 
Published: June 2021

Abstract
Background
Breastfeeding is the single, most cost-effective intervention to reduce worldwide child mortality. Women empowerment interventions have positive impacts on child and maternal nutritional, and health status. Women’s employment and economic participation in Ethiopia have shown progress over the past three decades. However, consistent evidence indicated that maternal employment is often negatively associated with optimal breastfeeding in Ethiopia. The existence and enforcement of breastfeeding law, arrangement, and support in the workplace have vital roles in protecting employed mothers’ ability and right to breastfeed upon return to work from maternity leave. This commentary compared the breastfeeding laws, policies, and arrangements in Ethiopia with international standards, recommendations, and evidence-based practices.

Workplace breastfeeding policies in Ethiopia
Public legislations of Ethiopia poorly protect the breastfeeding right of most new mothers. Ethiopian revised Labor Proclamation (No.1156/2019) incorporates most of the International Labour Organization maternity protection recommendations. However, it poorly safeguards breastfeeding rights and abilities of employed women. The provided maternity leave period is also shorter than the recommended exclusive breastfeeding duration. The revised Federal Civil Servant Proclamation of Ethiopia (NO.1064/2017) mandates the establishment of a nursery in government institutions where female civil servants could breastfeed and take care of their babies in a private room. Though, it protects only a small proportion of working mothers in Ethiopia, as majority women employed in the agriculture and informal economy sectors. So far, there are no notable workplace breastfeeding arrangements and support for employed mothers by employers and other initiatives. The ILO recommendation and experience of other middle income and low-income countries can be legal and practical grounds for establishment of breastfeeding-friendly workplace in Ethiopia.

Conclusions
The lack of workplace breastfeeding laws, arrangements, and supports in Ethiopia limits mothers’ right to practice optimal breastfeeding. Policymakers, the government, and all concerned bodies should give due attention to enacting and enforcing sound laws and arrangements that will enable employed mothers to practice optimal breastfeeding upon return to work.
Biportal endoscopic posterior lumbar decompression and vertebroplasty for extremely elderly patients affected by lower lumbar delayed vertebral collapse with lumbosacral radiculopathy
Authors: Kang Min-Seok , Heo Dong-Hwa , Chung Hoon-Jae , You Ki-Han , Kim Hyong-Nyun , Choi Jun-Young , Park Hyun-Jin 
Published: June 2021

Abstract
Background
Lower lumbar osteoporotic vertebral compression fracture in extremely elderly patients can often lead to lumbosacral radiculopathy (LSR) due to delayed vertebral collapse (DVC). Surgical intervention requires posterior instrumented lumbar fusion as well as vertebral augmentation or anterior column reconstruction depending on the cleft formation and intravertebral instability. However, it is necessary to decide on surgery in consideration of the patient’s frail status, surgical invasiveness, and rehabilitation. In the lower lumbar DVC without intravertebral instability, biportal endoscopic posterior lumbar decompression and vertebroplasty (BEPLD + VP) can be simultaneously attempted. This study aimed to assess the clinical outcomes of BEPLD + VP for the treatment of DVC-related LSR.

Methods
This retrospective case series enrolled 18 consecutive extremely elderly (aged ≥ 75-year-old) patients (6 men and 12 women) who had lower lumbar (at or below L3) DVC-related LSR. Patients who require anterior column reconstruction, such as cleft formation accompanied by intravertebral instability and patients who have not been followed for more than 6 months, were excluded from this study. All patients underwent BEPLD + VP under epidural anesthesia. Clinical results were evaluated by the visual analog scale (VAS) score and the modified Japanese Orthopedic Association (mJOA) scores.

Results
Most of the patients had DVC affecting level L4, with the deformation being a flat type or concave type rather than a wedge type. The VAS score (back and leg) significantly decreased from 7.78 ± 1.17 and 6.89 ± 1.13 preoperatively to 2.94 ± 0.64 and 2.67 ± 1.08 within 2 postoperative days (p < 0.001). The mJOA score significantly improved from 4.72 ± 1.27 preoperatively to 8.17 ± 1.15 in the final follow-up (p < 0.001). The mean recovery rate (RR) in the last follow-up was 56.07% ± 9.98. Incidental durotomy was reported in two patients and epidural hematomas in another two patients; however, all patients improved with conservative treatment, and no re-operation was required.

Conclusions
BELPD + VP was a type of salvage therapy that reduces surgical morbidity, requires major spine surgery under general anesthesia and provides good clinical outcomes in extremely elderly patients with DVC-related LSR.
Sleep and physical activity patterns in adults and children with Bardet–Biedl syndrome
Authors: Pomeroy Jeremy , VanWormer Jeffrey J. , Meilahn Jill R. , Maki Tara , Murali Hema R. , Haws Robert M. 
Published: June 2021

Abstract
Background
Overweight and obesity are common features of the rare disease Bardet–Biedl syndrome (BBS). Sleep and physical activity are behaviors that might impact overweight and obesity and thus may play a key role in the health and well-being of people with BBS. Objectively-measured sleep and physical activity patterns in people with BBS are not well known. We evaluated objectively-measured sleep and physical activity patterns in the largest cohort to date of people with BBS.

Results
Short sleep duration, assessed using wrist-worn accelerometers, was common in both children and adults with BBS. Only 7 (10%) of adults and 6 (8%) of children met age-specific sleep duration recommendations. Most adults 64 (90%) achieved recommended sleep efficiency. The majority of children 26 (67%) age 6–12 years achieved recommended sleep efficiency, but among children age 13–18, only 18 (47%). In both adults and children, sleep duration was significantly negatively correlated with duration of prolonged sedentary time. In children age 6–12 sleep duration was also significantly related to total activity score, children with lower sleep duration had lower total activity scores.

Conclusions
Insufficient sleep duration is very common in people with BBS. Prolonged sedentary time and short sleep duration are both potentially important health-related behaviors to target for intervention in people with BBS.
Sequential everolimus for angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study
Authors: Gu Liangyou , Peng Cheng , Zhang Fan , Fang Cunjin , Guo Gang 
Published: June 2021

AbstractBackgroundTo evaluate the efficacy, safety and health economics of sequential everolimus in treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC).MethodsIn this prospective cohort study, patients met the inclusion criteria received standard or sequential treatment according to their willingness. All patients received an initial dose of everolimus (10 mg oral, once a day) for 3 months. The standard treatment group maintained 10 mg QD for 12 months, while the sequential treatment group reduced the dose to 5 mg QD from the 4th month. The efficacy, serum everolimus concentration and safety were evaluated at 1, 3, 6, 9 and 12 months after treatment. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in the total volume of target AML relative to baseline.ResultsBetween June 1, 2016 and June 1, 2017, a total of 53 patients were included. Twenty-three patients received standard treatment, 30 patients received sequential treatment. At 1, 3, 6, 9 and 12 months after treatment, the proportion of patients whose total target tumor volume decreased by ≥ 50% from baseline was 39.1% versus 36.7%, 43.5% versus 56.7%, 47.8% versus 50%, 47.8% versus 60% and 47.8% versus 23.3% respectively (P > 0.05 for all). The overall response rate of skin lesions in the two groups was 40.4%, and the response rates of skin lesions at different times were similar for two groups (P > 0.05 for all). Major adverse effects (AEs) included mouth ulceration, hypertriglyceridemia, hypercholesterolemia, menstrual disorders. There was no significant difference between the two groups in the incidence of AEs at 3 months after treatment. The incidence of overall and grade 3/4 AEs at 12 months after treatment were significantly lower in the sequential treatment group. The average direct cost of the two groups in 12 months was $15,466 and $11,120, respectively.ConclusionsCompared to standard treatment, sequential treatment was equally effective, with a lower incidence of adverse events and a lower direct cost, suggesting that it may be an alternative treatment for AML associated with TSC.
Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report
Authors: Westenius Eini , Pettersson Maria , Björck Erik 
Published: June 2021

Abstract
Background
Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21.

Case presentation
We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal.

Conclusions
We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.
Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases
Authors: Pang Yu , Wang Chaohong , Tang Junxiang , Zhu Jiansheng 
Published: June 2021

Abstract
Objective
To assess the detection efficiency of noninvasive prenatal testing (NIPT) for fetal autosomal aneuploidy, sex chromosome aneuploidy (SCA), other chromosome aneuploidy, copy number variation (CNV), and to provide further data for clinical application of NIPT.

Materials and methods
25,517 pregnant women who underwent NIPT testing in Anhui Province Maternity and Child Health Hospital from September 2019 to September 2020 were selected, and samples with high-risk test results were subjected to karyotype analysis for comparison by using amniotic fluid, with some samples subjected to further validation by chromosomal microarray analysis, and followed up for pregnancy outcome.

Results
A total of 25,517 pregnant women who received NIPT, 25,502 cases were tested successfully, and 294 high-risk samples (1.15%) were detected, there were 96 true positive samples, 117 false positive samples and 81 cases were refused further diagnosis. Samples with high risk of autosomal aneuploidy were detected in 71 cases (0.28%), and 51 cases were confirmed, including: trisomy 21 (T21) in 44 cases, trisomy 18 (T18) in 5 cases, and trisomy 13 (T13) in 2 cases; the positive predictive value (PPV) was 91.67%, 45.45%, and 33.33%, respectively, and the negative predictive value was 100%, the false positive rate (FPR) was 0.02%, 0.02%, and 0.02%, respectively.13 samples with high risk of mosaic trisomies 21, 18, and 13 were detected, and 1 case of T21mos was confirmed with a PPV of 8.33%. Samples with high risk of SCA were detected in 72 cases (0.28%), and the diagnosis was confirmed in 23 cases, with a PPV of 41.07% and a FPR of 0.13%. These included 3 cases of 45,X, 6 cases of 47,XXY, 8 cases of 47,XXX and 6 cases of 47,XYY, with PPVs of 12.00%, 50.00%, 72.73%, and 75.00%, respectively, and false-positive rates of 0.09%, 0.02%, 0.01% and 0.01% respectively. Samples with high risk of CNV were detected in 104 cases (0.41%) and confirmed in 18 cases, with a PPV of 32.14% and a FPR of 0.15%. Samples with high risk of other chromosomal aneuploidy were detected in 34 cases (0.13%), and the diagnosis was confirmed in 3 cases, which were T2, T9, and T16 respectively. The overall PPV for other chromosome aneuploidy was 12.50%, with a FPR of 0.08%.

Conclusion
NIPT is indicated for trisomies 21, 18 and 13 screening, especially for T21. It also has some certain reference value for SCA and CNV, but is not recommended for screening of other chromosomal aneuploidy.
Molecular laterality encodes stress susceptibility in the medial prefrontal cortex
Authors: Chae Sujin , Hong Jiso , Kang Keunsoo , Shin Anna , Kim Dae-Gun , Lee Sinjeong , Kim Moo-young , Jung Inkyung , Kim Daesoo 
Published: June 2021

AbstractFunctional lateralization of the prefrontal cortex has been implicated in stress and emotional disorders, yet underlying gene expression changes remains unknown. Here, we report molecular signatures lateralized by chronic social defeats between the two medial prefrontal cortices (mPFCs). Stressed mice show 526 asymmetrically expressed genes between the mPFCs. This cortical asymmetry selectively occurs in stressed mice with depressed social activity, but not in resilient mice with normal behavior. We have isolated highly asymmetric genes including connective tissue growth factor (CTGF), a molecule that modulates wound healing at the periphery. Knockdown of CTGF gene in the right mPFC by shRNA led to a stress-resistant behavioral phenotype. Overexpression of CTGF in the right mPFC using viral transduction induces social avoidance while the left mPFC thereof prevent stress-induced social avoidance. Our study provides a molecular window into the mechanism of stress-induced socioemotional disorders, which can pave the way for new interventions by targeting cortical asymmetry.
The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia
Authors: Krüger Renata L. , Clark Cameron M. , Dyck Adrienna M. , Anderson Todd J. , Clement Fiona , Hanly Patrick J. , Hanson Heather M. , Hill Michael D. , Hogan David B. , Holroyd-Leduc Jayna , Longman R. Stewart , McDonough Meghan , Pike G. Bruce , Rawling Jean M. , Sajobi Tolulope , Poulin Marc J. 
Published: June 2021

Abstract
Background
There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months).

Methods
We will recruit 264 participants (aged 50–80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months).

Discussion
This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing.

Trial registration
ClinicalTrials.gov NCT03035851. Registered on 30 January 2017