bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial
Authors: Ryan Rebecca , Mussa Aamirah , Singtaa-Madliki Mandisa , Batting Joanne , Balakrishna Yusentha , Morroni Chelsea , Hofmeyr G. Justus 
Published: May 2022

IntroductionHormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18–35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial.MethodsWomen were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135).ResultsBaseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152–455), IUD 235 (168–426) and LNG 216 (153–419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163–467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97–193) pmol/L] was significantly lower than in both IUD (p &lt; 0.0001) and implant (p = 0.005) groups; and level in the implant group [156 (112–250) pmol/L] was significantly lower than in the IUD group (p = 0.004).ConclusionsAt 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods.ECHO Study RegistrationClinicalTrials.gov, identifier: NCT02550067.
The Downregulated Lipo-Related Gene Expression Pattern in Keloid Indicates Fat Graft Is a Potential Clinical Option for Keloid
Authors: Li Xueqing , Zhu Zhaowei , Xu Yangbin , Xu Shuqia 
Published: May 2022

BackgroundKeloids are a common complication of wounds, often manifesting with continuous hyperplasia and aggressive growth. Keloids also have a high recurrence rate and are largely resistant to treatment, making them clinically incurable, highlighting the need to translate basic research into clinical practice.Materials and MethodsWe used GSE158395 and GSE92566 as discovery datasets to identify specific enriched hub genes and lncRNAs associated with keloid development and progression. This data was then used to identify the competing endogenous RNAs (ceRNAs) in these pathways by using a bidirectional selection method. Then, all hub genes and lncRNAs in ceRNAs were validated using GSE90051, GSE178562, and GSE175866, which describe the transcriptional profiles of keloid tissues, fibroblasts from pathological scars, and keloid fibroblast subpopulations, respectively. The keloid tissues were measured with qPCR.ResultsBoth fat-associated biological processes and fat cell differentiation were enriched in the downregulated gene set. Further evaluation revealed that all 11 hub genes were lipo-related, and most of these were differentially expressed in all three validation datasets. We then identified a clear ceRNA network within the data comprising six hub genes and four lncRNAs. Evaluations of the validation datasets confirmed that all six of these hub genes and two of the four lncRNAs were downregulated in keloid tissues; two hub genes and one lncRNA were downregulated in fibroblasts from pathological scars; and five hub genes and one lncRNA were significantly downregulated in mesenchymal subpopulation. Three genes had statistical difference and eight genes showed downregulated trend through qPCR of the keloid tissue.ConclusionOur results suggest that keloid development relies on the downregulation of lipo-related genes and pre-adipocytes in diseased tissues and may be one of the key mechanisms underlying fat grafting-mediated treatment of pathological scarring.
Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
Authors: Jeitler R. , Glader C. , Tetyczka C. , Zeiringer S. , Absenger-Novak M. , Selmani A. , Fröhlich E. , Roblegg E. 
Published: May 2022

Lipid-based nanosystems enable intracellular delivery of drugs in the oral cavity for the treatment of local diseases. To rationally design such systems, suitable matrix compositions and particle properties need to be identified, and manufacturing technologies that allow reproducible production have to be applied. This is a prerequisite for the reliable and predictable performance of in-vitro biological studies. Here, we showed that solid lipid nanoparticles (SLN, palmitic acid) and nanostructured lipid carriers (NLC, palmitic acid and oleic acid in different ratios) with a size of 250 nm, a negative zeta potential, and a polydispersity index (PdI) of less than 0.3 can be reproducibly prepared by high-pressure homogenization using quality by design and a predictive model. SLN and NLC were colloidally stable after contact with physiological fluid and did not form agglomerates. The in-vitro studies clearly showed that besides particle size, surface charge and hydrophobicity, matrix composition had a significant effect. More specifically, the addition of the liquid lipid oleic acid increased the cellular uptake capacity without changing the underlying uptake mechanism. Regardless of the matrix composition, caveolin-mediated endocytosis was the major route of uptake, which was confirmed by particle localization in the endoplasmic reticulum. Thus, this work provides useful insights into the optimal composition of lipid carrier systems to enhance the intracellular uptake capacity of drugs into the oral mucosa.
Eosinophils, Stroke-Associated Pneumonia, and Outcome After Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Guo Zhiliang , Hou Jie , Yu Shuai , Zhang Hang , Yu Shuhong , Wang Huaishun , Xu Jiaping , You Shoujiang , Huang Zhichao , Xiao Guodong , Cao Yongjun , Liu Chun-Feng 
Published: May 2022

BackgroundEosinophils contribute to antibacterial defense by releasing mitochondrial DNA, which are decreased in patients with acute ischemic stroke (AIS). However, the impact of eosinophils on stroke-associated pneumonia (SAP) among patients with AIS remains unclear. Moreover, whether SAP is in the path of the association between eosinophils and clinical outcomes also remains unclear. We aimed to assess the relationships between eosinophils, SAP, and clinical outcome after mechanical thrombectomy in patients with AIS.MethodsA total of 328 consecutive patients with AIS who underwent mechanical thrombectomy between May 2017 and March 2021 were analyzed. Their baseline data and peripheral eosinophil counts were recorded on admission. Regression analysis was used to assess the effect of eosinophils on SAP, and its effect on poor outcome is defined as a modified Rankin Scale score of 3–6 at month 3 after admission. Mediation analysis was utilized to assess the proportion of the total effect of SAP on the association between eosinophils and poor outcomes.ResultsMultivariate analysis revealed that eosinophils was independently associated with SAP after adjusting for potential confounders (odds ratio, 0.00; 95% CI, 0.00–0.38; P = 0.0267), which are consistent with the result of eosinophils (dichotomous) as a categorical variable (odds ratio, 0.54; 95% CI, 0.31–0.96; P = 0.0342). A non-linear relationship was detected between eosinophils and SAP, whose inflection point was 0.06. Subgroup analyses further confirmed these associations. Eosinophils were also associated with poor outcomes (odds ratio, 0.00; 95% CI, 0.00–0.14; P = 0.0124). Additionally, mediation analysis found that SAP partially mediated the negative relationship between eosinophils and poor outcome (indirect effect = −0.169; 95% CI:−0.339 –−0.040, P &lt; 0.001).ConclusionOur findings suggested that a lower eosinophil level was associated with higher SAP and poorer outcome, and SAP might play an important effect in the association between eosinophils and poor outcomes.
Effects of Intermittent Hypoxia in Training Regimes and in Obstructive Sleep Apnea on Aging Biomarkers and Age-Related Diseases: A Systematic Review
Authors: Tessema Belay , Sack Ulrich , König Brigitte , Serebrovska Zoya , Egorov Egor 
Published: May 2022

Several studies have assessed the effects of intermittent hypoxia-normoxia training (IHNT), intermittent hypoxia-hyperoxia training (IHHT), and obstructive sleep apnea (OSA) on aging and age-related diseases in humans; however, the results remain contradictory. Therefore, this review aims to systematically summarize the available studies on the effects of IHNT, IHHT, and OSA on aging and age-related diseases. Relevant studies were searched from PubMed, Google Scholar, Cochrane Library databases, and through manual searching from reference lists of eligible studies. A total of 38 eligible studies were included in this systematic review. IHHT and IHNT provide positive effects on several age-related parameters including quality of life, cognitive and physical functions, plasma level of glucose and cholesterol/LDL, systolic blood pressure, red blood cells, and inflammation. Moreover, moderate intermittent hypoxia induces telomerase reverse transcriptase (TERT) activity and telomere stabilization, delays induction of senescence-associated markers expression and senescence-associated β-galactosidase, upregulates pluripotent marker (Oct4), activates a metabolic shift, and raises resistance to pro-apoptotic stimuli. On the contrary, intermittent hypoxia in OSA causes hypertension, metabolic syndrome, vascular function impairment, quality of life and cognitive scores reduction, advanced brain aging, increase in insulin resistance, plasma hydrogen peroxide, GSH, IL-6, hsCRP, leptin, and leukocyte telomere shortening. Thus, it can be speculated that the main factor that determines the direction of the intermittent hypoxia action is the intensity and duration of exposure. There is no direct study to prove that IHNT/IHHT actually increases life expectancy in humans. Therefore, further study is needed to investigate the actual effect of IHNT/IHHT on aging in humans.Systematic Review Registrationwww.crd.york.ac.uk/prospero, identifier CRD42022298499.
Development of Unilateral Peri-Lead Edema Into Large Cystic Cavitation After Deep Brain Stimulation: A Case Report
Authors: Lu Yue , Qiu Chang , Chang Lei , Luo Bei , Dong Wenwen , Zhang Wenbin , Sun Hai-Hua 
Published: May 2022

Background and ImportanceDeep brain stimulation (DBS) has been approved to treat a variety of movement disorders, including Parkinson's disease (PD), essential tremor, and dystonia. Following the DBS surgery, some perioperative and even delayed complications due to intracranial and hardware-related events could occur, which may be life-threatening and require immediate remedial measures.Clinical PresentationWe report a case of an older woman with advanced PD who developed the unique complication of unilateral cyst formation at the tip of the DBS electrode after undergoing bilateral placement of subthalamic nucleus DBS. After a period of controlled motor symptoms, the patient showed new neurological deficits related to right peri-lead edema. However, the new neurological symptoms regressed quickly over several days with stereotactic implantation of a puncture needle to drain the cyst fluid without removing the affected lead.ConclusionThe occurrence of an intraparenchymal cyst following DBS surgery is a rare but life-threatening complication that could relate to edema around the electrodes or cerebrospinal fluid tracking. Stereotactic aspiration makes the intracranial cyst regress safely and effectively and ensures that the electrode is in the optimal position of the target nucleus to achieve an effective DBS surgery.
The Clinical Utility of the MOCA in iNPH Assessment
Authors: Wesner Eric , Etzkorn Lacey , Bakre Shivani , Chen Jinyu , Davis Alexander , Zhang Yifan , Yasar Sevil , Rao Aruna , Luciano Mark , Wang Jiangxia , Moghekar Abhay 
Published: May 2022

ObjectivesWe sought to estimate reliable change thresholds for the Montreal Cognitive Assessment (MoCA) for older adults with suspected Idiopathic Normal Pressure Hydrocephalus (iNPH). Furthermore, we aimed to determine the likelihood that shunted patients will demonstrate significant improvement on the MoCA, and to identify possible predictors of this improvement.MethodsPatients (N = 224) presenting with symptoms of iNPH were given a MoCA assessment at their first clinic visit, and also before and after tap test (TT) or extended lumbar drainage (ELD). Patients who were determined to be good candidates for shunts (N = 71, 31.7%) took another MoCA assessment following shunt insertion. Reliable change thresholds for MoCA were derived using baseline visit to pre-TT/ELD assessment using nine different methodologies. Baseline characteristics of patients whose post-shunt MoCA did and did not exceed the reliable change threshold were compared.ResultsAll nine of reliable change methods indicated that a 5-point increase in MoCA would be reliable for patients with a baseline MoCA from 16 to 22 (38.4% of patients). Furthermore, a majority of reliable change methods indicated that a 5-point increase in MoCA would be reliable for patients with a baseline MoCA from 14 to 25. Reliable change thresholds varied across methods from 4 to 7 points for patients outside of this range. 10.1% had at least a 5-point increase from baseline to post-TT/ELD. Compared to patients who did not receive a shunt, patients who received a shunt did not have lower average MoCA at baseline (p = 0.88) or have better improvement in MoCA scores after the tap test (p = 0.17). Among shunted patients, 23.4% improved by at least 5 points on the MoCA from baseline to post-shunt. Time since onset of memory problems and post-TT/ELD gait function were the only clinical factors significantly associated with having a reliable change in MoCA after shunt insertion (p = 0.019; p = 0.03, respectively).ConclusionsIn patients with iNPH, clinicians could consider using a threshold of 5 points for determining whether iNPH-symptomatic patients have experienced cognitive benefits from cerebrospinal fluid drainage at an individual level. However, a reliable change cannot be detected for patients with a baseline MoCA of 26 or greater, necessitating a different cognitive assessment tool for these patients.
Central Retinal Artery Occlusion: Current Practice, Awareness and Prehospital Delays in Switzerland
Authors: Ardila Jurado Elena , Sturm Veit , Brugger Florian , Nedeltchev Krassen , Arnold Marcel , Bonati Leo H. , Carrera Emmanuel , Michel Patrik , Cereda Carlo W. , Bolognese Manuel , Albert Sylvan , Medlin Friedrich , Berger Christian , Schelosky Ludwig , Renaud Susanne , Niederhauser Julien , Bonvin Christophe , Mono Marie-Luise , Rodic Biljana , Tarnutzer Alexander A. , Schwegler Guido , Salmen Stephan , Luft Andreas R. , Peters Nils , Vehoff Jochen , Kägi Georg ,   The Swiss Stroke Registry Investigators
Published: May 2022

Background and PurposeCentral retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO.Methods(1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland.ResultsThree hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy.ConclusionsCRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO.
Upper Limb Stroke Rehabilitation Using Surface Electromyography: A Systematic Review and Meta-Analysis
Authors: Munoz-Novoa Maria , Kristoffersen Morten B. , Sunnerhagen Katharina S. , Naber Autumn , Alt Murphy Margit , Ortiz-Catalan Max 
Published: May 2022

BackgroundUpper limb impairment is common after stroke, and many will not regain full upper limb function. Different technologies based on surface electromyography (sEMG) have been used in stroke rehabilitation, but there is no collated evidence on the different sEMG-driven interventions and their effect on upper limb function in people with stroke.AimSynthesize existing evidence and perform a meta-analysis on the effect of different types of sEMG-driven interventions on upper limb function in people with stroke.MethodsPubMed, SCOPUS, and PEDro databases were systematically searched for eligible randomized clinical trials that utilize sEMG-driven interventions to improve upper limb function assessed by Fugl-Meyer Assessment (FMA-UE) in stroke. The PEDro scale was used to evaluate the methodological quality and the risk of bias of the included studies. In addition, a meta-analysis utilizing a random effect model was performed for studies comparing sEMG interventions to non-sEMG interventions and for studies comparing different sEMG interventions protocols.ResultsTwenty-four studies comprising 808 participants were included in this review. The methodological quality was good to fair. The meta-analysis showed no differences in the total effect, assessed by total FMA-UE score, comparing sEMG interventions to non-sEMG interventions (14 studies, 509 participants, SMD 0.14, P 0.37, 95% CI –0.18 to 0.46, I255%). Similarly, no difference in the overall effect was found for the meta-analysis comparing different types of sEMG interventions (7 studies, 213 participants, SMD 0.42, P 0.23, 95% CI –0.34 to 1.18, I273%). Twenty out of the twenty-four studies, including participants with varying impairment levels at all stages of stroke recovery, reported statistically significant improvements in upper limb function at post-sEMG intervention compared to baseline.ConclusionThis review and meta-analysis could not discern the effect of sEMG in comparison to a non-sEMG intervention or the most effective type of sEMG intervention for improving upper limb function in stroke populations. Current evidence suggests that sEMG is a promising tool to further improve functional recovery, but randomized clinical trials with larger sample sizes are needed to verify whether the effect on upper extremity function of a specific sEMG intervention is superior compared to other non-sEMG or other type of sEMG interventions.
Long-Term Patient Satisfaction and Quality of Life Following Breast Reconstruction Using the BREAST-Q: A Prospective Cohort Study
Authors: Shiraishi Makoto , Sowa Yoshihiro , Tsuge Itaru , Kodama Takuya , Inafuku Naoki , Morimoto Naoki 
Published: May 2022

BackgroundBreast reconstruction is a promising surgical technique to improve health-related quality of life (HRQoL) in patients with breast cancer. However, the long-term risk factors associated with HRQoL after breast surgery are still unclear. Our aim was to evaluate breast satisfaction and HRQoL following breast reconstruction to identify clinical factors associated with each domain of BREAST-Q in the long-term.MethodsPatient-reported BREAST-Q outcomes were analyzed 1 and 5 years after breast reconstruction in a single-blinded, prospective study. Multiple regression analysis was performed to identify the risk and protective factors associated with BREAST-Q scores. These scores at 1 and 5 years were also compared across three types of operation: mastectomy only, tissue expander/implant (TE/Imp), and a deep inferior epigastric perforator (DIEP) flap.ResultsSurveys were completed by 141 subjects after 1 year and 131 subjects after 5 years. Compared to mastectomy only, breast reconstruction was significantly associated with greater “Satisfaction with breasts” (TE/Imp, p &lt; 0.001; DIEP, p &lt; 0.001) and “Psychosocial well-being” (TE/Imp, p &lt; 0.001; DIEP, p &lt; 0.001), higher body mass index (BMI) resulted in lower “Satisfaction with breasts” (p = 0.004), and a history of psychiatric or neurological medication was significantly associated with “Physical well-being” at 1-year postoperatively (p = 0.02). At 5 years, reconstructive procedures were significantly positively associated with greater “Satisfaction with breasts” (TE/Imp, p &lt; 0.001; DIEP, p &lt; 0.001) and “Psychosocial well-being” (TE/Imp, p = 0.03; DIEP, p &lt; 0.001), and a bilateral procedure was a significant risk factor for lower “Psychosocial well-being” (p = 0.02).ConclusionsThe results of this study show that breast reconstruction improves “Satisfaction with Breasts” and “Psychosocial well-being” compared to mastectomy. Among all three types of operation, DIEP gave the best scores at 5 years postoperatively. Thus, autologous reconstruction is recommended for promotion of long-term HRQoL after breast surgery.
Inequality in Accessibility of Proton Therapy for Cancers and Its Economic Determinants: A Cross-Sectional Study
Authors: Xia Zhongying , Wang Junfeng , Xia Jiaxin , Wang Menglei , Cheng Zhiqiang 
Published: May 2022

BackgroundCancer is a leading cause of death in the world, and the estimated new cancer cases were 19 million and the estimated cancer deaths were around 10 million worldwide in 2020. Proton therapy (PT) is a promising treatment for cancers; however, only few patients with cancer received PT due to limited number of PT centers worldwide, especially in low- and middle-income countries.Methods and ResultsCross-sectional country level data were collected from publicly available information. Lorenz curves and Gini coefficient were used to assess the inequality in accessing to PT, and zero-inflated Poisson models were used to investigate the determinants of number of PT facilities in each country. The Gini coefficients were 0.96 for PT centers and 0.96 for PT chambers, which indicated high level of inequality. Total GDP had a significant impact on whether a country had a practical PT center, whereas total GDP and GDP per capita had significant impacts on the number of PT centers.ConclusionExtremely high inequality exists in accessibility of PT centers among all countries in the world. Economic development was the most important factor determining the adoption of PT; thus, with the growth in global economics, more PT centers can be expected in near future.