bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreasing myopic lacquer crack and widening parapapillary gamma zone: case report
Authors: Jonas Rahul A. , Wei Chuan Chuan , Jonas Jost B. , Wang Ya Xing 
Published: December 2021

Abstract
Background
Myopic axial elongation may be due to an equatorial enlargement of Bruch’s membrane (BM), leading to a prolate eye shape and increasing strain with BM and the retinal pigment epithelium (RPE) layer at the posterior pole. The increased BM strain may cause an enlargement of Bruch’s membrane opening (BMO) of the optic nerve head, with the subsequent development and enlargement of parapapillary gamma zone as BM-free parapapillary zone. The increased strain within BM and RPE may also cause lacquer cracks (LCs) as linear breaks in the RPE and / or BM. Studies suggested that a more marked gamma zone enlargement is associated with lower prevalence of LCs or macular BM defects. Here report on the disappearance of a LC during a 10-year follow-up of a highly myopic eye, concurrent with a marked increase in gamma zone.

Case presentation
A 56-year-old woman showed in her right eye (axial length measured 30.69 mm) a LC, vertically oval optic disc, and parapapillary gamma zone in 2001. When re-examined in 2006, gamma zone had enlarged, while the LC was no longer detectable. In 2011, the LC was not visible neither upon ophthalmoscopy and or upon optical coherence tomography (OCT), while gamma zone had further enlarged. The gamma zone enlargement occurred in a direction perpendicular to the direction of the former LC.

Conclusions
The observation suggest that a LC can decrease in width, in temporal association with an enlargement of gamma zone. It fits with the notion that an enlargement of the BMO (i.e., enlarging gamma zone) may lead to a relaxation of the BM strain and subsequently to a decrease in the width of the LC.
Multi modal imaging in corneal edema after corneal collagen cross-linking (CXL); a case-based literature review
Authors: Soleimani Mohammad , Ebrahimi Zohre , Moghadam Mohammad Yazdani , Shahriari Mansoor , Behzadfar Sara , Ramezani Bahareh , Cheraqpour Kasra 
Published: December 2021

Abstract
Background
Keratoconus (KCN) is a common ectatic disorder of the cornea. Corneal collagen cross-linking (CXL) is used as an effective option to slowdown the disease progression. Although CXL is considered a safe procedure, corneal endothelial damage, especially in corneal thickness of less than 400 μm, has been reported.

Case presentation
A 25-year-old man known case of KCN was referred with complaints about blurred vision and discomfort of the right eye 3 days after performing CXL. The preoperative thinnest point was 461 μm. His presenting BCVA was CF at 1 m. Examination showed central corneal edema and stromal haziness. ASOCT demonstrated increased central corneal thickness and very deep CXL line. In the confocal scan, anterior stroma showed hyper-reflective lines without recognizable cells and nerves, the middle stroma showed rare active and edematous keratocytes and a hyper-reflective reticular pattern with elongated keratocytes and needle-like structures involving the posterior stroma indicated increased depth of CXL. To manage the patient, debridement of loosened epithelium was done. Non-preservative steroid 1% eye drop was prescribed frequently. The corneal edema was completely resolved during 2 months with no need for surgical procedure and BCVA of 20/30 in his right eye.

Conclusion
The corneal thickness of more than 400 μm cannot guarantee the absence of corneal edema after corneal collagen cross-linking, which can pertain to several factors such as inadvertently using of higher energy as well as the incorrect observance of all guidelines, instructions, and other precautions, even by a trained surgeon.
Women and ethnoracial minorities with poor cardiovascular health measures associated with a higher risk of developing mood disorder
Authors: Guo Aixia , Stephens Kari A. , Khan Yosef M. , Langabeer James R. , Foraker Randi E. 
Published: December 2021

Abstract
Background
Mood disorders (MDS) are a type of mental health illness that effects millions of people in the United States. Early prediction of MDS can give providers greater opportunity to treat these disorders. We hypothesized that longitudinal cardiovascular health (CVH) measurements would be informative for MDS prediction.

Methods
To test this hypothesis, the American Heart Association’s Guideline Advantage (TGA) dataset was used, which contained longitudinal EHR from 70 outpatient clinics. The statistical analysis and machine learning models were employed to identify the associations of the MDS and the longitudinal CVH metrics and other confounding factors.

Results
Patients diagnosed with MDS consistently had a higher proportion of poor CVH compared to patients without MDS, with the largest difference between groups for Body mass index (BMI) and Smoking. Race and gender were associated with status of CVH metrics. Approximate 46% female patients with MDS had a poor hemoglobin A1C compared to 44% of those without MDS; 62% of those with MDS had poor BMI compared to 47% of those without MDS; 59% of those with MDS had poor blood pressure (BP) compared to 43% of those without MDS; and 43% of those with MDS were current smokers compared to 17% of those without MDS.

Conclusions
Women and ethnoracial minorities with poor cardiovascular health measures were associated with a higher risk of development of MDS, which indicated the high utility for using routine medical records data collected in care to improve detection and treatment for MDS among patients with poor CVH.
Cost-effectiveness analysis of a chronic back pain multidisciplinary biopsychosocial rehabilitation (MBR) compared to standard care for privately insured in Germany
Authors: Hochheim M. , Ramm P. , Wunderlich M. , Amelung V. 
Published: December 2021

Abstract
Background
Multidisciplinary biopsychosocial rehabilitation (MBR) is highly recommended for chronic lower back pain (CLBP) treatment, but its economic benefit remains to be clearly demonstrated. The purpose of this study is to analyse the effect of a 12-month MBR programme of behavioural change coaching and device-supported exercise on direct medical costs, sick leave and health-related quality of life (HRQOL) at 24 months.

Methods
An incremental cost-effectiveness analysis was conducted in Germany from a private health insurance perspective using data from a multi-centre, two-arm randomised controlled trial with parallel-group Zelen's randomisation and 24-month follow-up. After removing dissimilarities in characteristics between MBR and usual care (control) via propensity score matching, treatment effects were calculated using a difference-in-difference approach.

Results
Base-case analysis of the MBR (n=112) and usual care group (n=111) showed an incremental cost-effectiveness ratio (ICER) of €8,296 per quality-adjusted life year (QALY) gained, indicating that the intervention was cost-effective. Compared to the controls, MBR reduced economically unaccounted sick leave due to back pain in the last six months by 17.5 days (p = 0.001) and had a positive effect on health-related quality of life (HRQOL) (0.046, p=0.026). Subgroup analysis of participants with major impairment demonstrated that a dominant intervention was possible, as reflected by an ICER of - €7,302 per QALY. Savings were driven by a - €1,824 reduction in back pain-specific costs. Moreover, sick leave was 27 days (p = 0.006) less in the MBR group.

Conclusions
This first cost-effectiveness study with combined data from a private health insurer and a controlled trial in Germany demonstrated that long term MBR for the treatment of CLBP is cost-effective. Subgroups with major impairment from back pain benefitted more from the intervention than those with minor impairment. MBR significantly reduced sick leave in all participants. Hence, it is a profitable intervention from a societal point of view.

Trial registration
The trial of the evaluation study was retrospectively registered in the German Clinical Trials Register under trial number DRKS00015463 retrospectively (dated 4 Sept 2018).
Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda
Authors: Ebong Chris , Sserwanga Asadu , Namuganga Jane Frances , Kapisi James , Mpimbaza Arthur , Gonahasa Samuel , Asua Victor , Gudoi Sam , Kigozi Ruth , Tibenderana James , Bwanika John Bosco , Bosco Agaba , Rubahika Denis , Kyabayinze Daniel , Opigo Jimmy , Rutazana Damian , Sebikaari Gloria , Belay Kassahun , Niang Mame , Halsey Eric S. , Moriarty Leah F. , Lucchi Naomi W. , Souza Samaly S. Svigel , Nsobya Sam L. , Kamya Moses R. , Yeka Adoke 
Published: December 2021

Abstract
Background
In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019.

Methods
This was a randomized, open-label, phase IV clinical trial. Children aged 6 months to 10 years with uncomplicated falciparum malaria were randomly assigned to treatment with AL or DP and followed for 28 and 42 days, respectively. Genotyping was used to distinguish recrudescence from new infection, and a Bayesian algorithm was used to assign each treatment failure a posterior probability of recrudescence. For monitoring resistance, Pfk13 and Pfmdr1 genes were Sanger sequenced and plasmepsin-2 copy number was assessed by qPCR.

Results
There were no early treatment failures. The uncorrected 28-day cumulative efficacy of AL ranged from 41.2 to 71.2% and the PCR-corrected cumulative 28-day efficacy of AL ranged from 87.2 to 94.4%. The uncorrected 28-day cumulative efficacy of DP ranged from 95.8 to 97.9% and the PCR-corrected cumulative 28-day efficacy of DP ranged from 98.9 to 100%. The uncorrected 42-day efficacy of DP ranged from 73.5 to 87.4% and the PCR-corrected 42-day efficacy of DP ranged from 92.1 to 97.5%. There were no reported serious adverse events associated with any of the regimens. No resistance-associated mutations in the Pfk13 gene were found in the successfully sequenced samples. In the AL arm, the NFD haplotype (N86Y, Y184F, D1246Y) was the predominant Pfmdr1 haplotype, present in 78 of 127 (61%) and 76 of 110 (69%) of the day 0 and day of failure samples, respectively. All the day 0 samples in the DP arm had one copy of the plasmepsin-2 gene.

Conclusions
DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda. Recurrent infections with AL were common. In Busia and Arua, the 95% confidence interval for PCR-corrected AL efficacy fell below 90%. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended.
Trial registration The trail was also registered with the ISRCTN registry with study Trial No. PACTR201811640750761
Biomimetic nanoparticles blocking autophagy for enhanced chemotherapy and metastasis inhibition via reversing focal adhesion disassembly
Authors: Shi Yesi , Lin Gan , Zheng Huili , Mu Dan , Chen Hu , Lu Zhixiang , He Pan , Zhang Yang , Liu Chao , Lin Zhongning , Liu Gang 
Published: December 2021

Abstract
Background
Autophagy is a conserved catabolic process, which plays an important role in regulating tumor cell motility and degrading protein aggregates. Chemotherapy-induced autophagy may lead to tumor distant metastasis and even chemo-insensitivity in the therapy of hepatocellular carcinoma (HCC). Therefore, a vast majority of HCC cases do not produce a significant response to monotherapy with autophagy inhibitors.

Results
In this work, we developed a biomimetic nanoformulation (TH-NP) co-encapsulating Oxaliplatin (OXA)/hydroxychloroquine (HCQ, an autophagy inhibitor) to execute targeted autophagy inhibition, reduce tumor cell migration and invasion in vitro and attenuate metastasis in vivo. The tumor cell-specific ligand TRAIL was bioengineered to be stably expressed on HUVECs and the resultant membrane vesicles were wrapped on OXA/HCQ-loaded PLGA nanocores. Especially, TH-NPs could significantly improve OXA and HCQ effective concentration by approximately 21 and 13 times in tumor tissues compared to the free mixture of HCQ/OXA. Moreover, the tumor-targeting TH-NPs released HCQ alkalized the acidic lysosomes and inhibited the fusion of autophagosomes and lysosomes, leading to effective blockade of autophagic flux. In short, the system largely improved chemotherapeutic performance of OXA on subcutaneous and orthotopic HCC mice models. Importantly, TH-NPs also exhibited the most effective inhibition of tumor metastasis in orthotopic HCCLM3 models, and in the HepG2, Huh-7 or HCCLM3 metastatic mice models. Finally, we illustrated the enhanced metastasis inhibition was attributed to the blockade or reverse of the autophagy-mediated degradation of focal adhesions (FAs) including E-cadherin and paxillin.

Conclusions
TH-NPs can perform an enhanced chemotherapy and antimetastatic effect, and may represent a promising strategy for HCC therapy in clinics.

Graphical Abstract
Multifunctional carbonized nanogels to treat lethal acute hepatopancreatic necrosis disease
Authors: Yen Shao-Chieh , Mao Ju-Yi , Lin Hung-Yun , Huang Huai-Ting , Harroun Scott G. , Nain Amit , Chang Huan-Tsung , Lin Han-You , Chen Li-Li , Huang Chih-Ching , Lin Han-Jia 
Published: December 2021

AbstractBackgroundShrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteriaVibrio parahaemolyticus(V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse.MethodsMild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 ℃ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules.ResultsDAO/DEX-CNGs manifest broad-spectrum antibacterial activity againstVibrio parahaemolyticusresponsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition ofVibrioin the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severeV. parahaemolyticusinfection, revealing that CNGs can effectively guard shrimp fromVibrioinvasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed.ConclusionOur work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrioagents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.Graphical Abstract
Widening or narrowing income inequalities in myocardial infarction? Time trends in life years free of myocardial infarction and after incidence
Authors: Tetzlaff Juliane , Tetzlaff Fabian , Geyer Siegfried , Sperlich Stefanie , Epping Jelena 
Published: December 2021

Abstract
Background
Despite substantial improvements in prevention and therapy, myocardial infarction (MI) remains a frequent health event, causing high mortality and serious health impairments. Previous research lacks evidence on how social inequalities in incidence and mortality risks developed over time, and on how these developments affect the lifespan free of MI and after MI in different social subgroups. This study investigates income inequalities in MI-free life years and life years after MI and whether these inequalities widened or narrowed over time.

Methods
The analyses are based on claims data of a large German health insurance provider insuring approximately 2.8 million individuals in the federal state Lower Saxony. Trends in income inequalities in incidence and mortality were assessed for all subjects aged 60 years and older by comparing the time periods 2006–2008 and 2015–2017 using multistate survival models. Trends in the number of life years free of MI and after MI were calculated separately for income groups by applying multistate life table analyses.

Results
MI incidence and mortality risks decreased over time, but declines were strongest among men and women in the higher-income group. While life years free of MI increased in men and women with higher incomes, no MI-free life years were gained in the low-income group. Among men, life years after MI increased irrespective of income group.

Conclusions
Income inequalities in the lifespan spent free of MI and after MI widened over time. In particular, men with low incomes are disadvantaged, as life years spent after MI increased, but no life years free of MI were gained.
Periodontal disease increases the host susceptibility to COVID-19 and its severity: a Mendelian randomization study
Authors: Wang Yi , Deng Hui , Pan Yihuai , Jin Lijian , Hu Rongdang , Lu Yongyong , Deng Wenhai , Sun Weijian , Chen Chengshui , Shen Xian , Huang Xiu-Feng 
Published: December 2021

Abstract
Background
Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity.

Methods
Summary statistics of COVID-19 susceptibility and severity were retrieved from the COVID-19 Host Genetics Initiative and used as outcomes. Single nucleotide polymorphisms associated with PD in Genome-wide association study were included as exposure. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy, including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations.

Results
The MR estimates showed that PD was significantly associated with significantly higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017, 95% CI 1.004–1.045) and weighted median method (OR = 1.029, P = 0.024, 95% CI 1.003–1.055). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW, OR = 1.025, P = 0.039, 95% CI 1.001–1.049; weighted median, OR = 1.030, P = 0.027, 95% CI 1.003–1.058). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19.

Conclusions
We provide evidence on the possible causality of PD accounting for the susceptibility and severity of COVID-19, highlighting the importance of oral/periodontal healthcare for general wellbeing during the pandemic and beyond.
Ethnobotanical study of medicinal plants in Adwa District, Central Zone of Tigray Regional State, Northern Ethiopia
Authors: Tahir Muhidin , Gebremichael Letebrhan , Beyene Tadesse , Van Damme Patrick 
Published: December 2021

Abstract
Background
Medicinal plants have been used for ages in Ethiopia. Some 887 plant species have been documented to heal human and livestock health problems. Documenting the traditional use of medicinal plants is a vital step in obtaining information on bioactive chemicals, preserving indigenous knowledge and ultimately interesting, medicinal plant species. We conducted this study with the aim of documenting the ethnobotanical knowledge associated with medicinal plant use in Adwa District, Northern Ethiopia.

Methods
The study was conducted from September 2018 to December 2019. A total of 393 informants (242 males and 151 females) were selected. Data were collected using semi-structured interviews, guided walks and group discussions. We calculated informant consensus factors (ICF) and fidelity level (FL) and performed ranking and paired comparisons. Data were analysed using descriptive statistics, including independent sample t test and ANOVA.

Results
Overall, we documented 127 medicinal plants belonging to 105 genera, under 54 families to be used by local people to address 43 human and 15 livestock ailments. Families Fabaceae and Solanaceae were the most important ones with 11 (8.66%) species each. Herbs were the dominant growth form (55 species), followed by shrubs (39). The most frequently used plant parts were leaves (24.27%) followed by roots (14%). The most important preparation method was crushing and pounding (42.7%) followed by fumigation (smoke and vapour) (23, 11.1%). The common route of administration was via skin application (67 or 32%) followed by oral (63, 27%). ICF showed that tonsillitis had the higher value (0.95). Cucumis ficifolius A. Rich. was the most preferred medicinal plant (36) treating abdominal pain, followed by Kalanchoe quartiniana A. Rich. for blackleg (34).

Conclusions
Adwa District is relatively rich in medicinal plant diversity and traditional knowledge on use, preparation and application of the medicinal flora. However, agricultural expansion (51%), overgrazing (43%) and drought (37%) were mentioned most when informants were asked about the threats to medicinal plants in Adwa District. Hence, on-site and off-site medicinal plant conservation would help protect medicinal plants in the district.