bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding CLL biology through mouse models of human genetics
Authors: ten Hacken Elisa , Wu Catherine J.
Published: December 2021

Rapid advances in large-scale next-generation sequencing studies of human samples have progressively defined the highly heterogeneous genetic landscape of chronic lymphocytic leukemia (CLL). At the same time, the numerous challenges posed by the difficulties in rapid manipulation of primary B cells and the paucity of CLL cell lines have limited the ability to interrogate the function of the discovered putative disease “drivers,” defined in human sequencing studies through statistical inference. Mouse models represent a powerful tool to study mechanisms of normal and malignant B-cell biology and for preclinical testing of novel therapeutics. Advances in genetic engineering technologies, including the introduction of conditional knockin/knockout strategies, have opened new opportunities to model genetic lesions in a B-cell–restricted context. These new studies build on the experience of generating the MDR mice, the first example of a genetically faithful CLL model, which recapitulates the most common genomic aberration of human CLL: del(13q). In this review, we describe the application of mouse models to the studies of CLL pathogenesis and disease transformation from an indolent to a high-grade malignancy (ie, Richter syndrome [RS]) and treatment, with a focus on newly developed genetically inspired mouse lines modeling recurrent CLL genetic events. We discuss how these novel mouse models, analyzed using new genomic technologies, allow the dissection of mechanisms of disease evolution and response to therapy with greater depth than previously possible and provide important insight into human CLL and RS pathogenesis and therapeutic vulnerabilities. These models thereby provide valuable platforms for functional genomic analyses and treatment studies.
The efficacy of fosfomycin trometamol in prevention of postoperative urinary tract infection in pregnant women after endoscopic procedures: open clinical trial
Authors: Radwan Mohamed , Hagras Ayman , Nagla Salah , Elhamamy Nareman , Abou Farha Mohammed
Published: December 2021

Background

Fosfomycin tromethamine is recommended (category B) for the treatment of urinary tract infections in pregnant women. We aimed to evaluate the efficacy of single-dose preoperative fosfomycin tromethamine in the prevention of urinary tract infection in pregnant women who underwent lower urinary tract endoscopic surgeries.

Methodology

The subjects of this study were pregnant women who underwent lower urinary tract endoscopic procedures. All patients received Fosfomycin tromethamine1 packet (3 g) dissolved in water the day before surgery. Routine pre- and postoperative urine analysis and urine cultures were performed when needed. Patients were monitored for urinary tract infections and the side effects of the drug. Moreover, maternal and fetal complications were monitored.

Results

The study was conducted on 31 pregnant women with a mean age of 24.48 ± 5.35 years. The endoscopic procedures were as follows: 28 (90.3%) DJ ureteric insertions for hydronephrosis, 2 (6.5%) urinary bladder stones, and cystoscopy (3.2%) for gross hematuria. Two (6.5%) patients had postoperative asymptomatic bacteriuria that resolved with oral antibiotic therapy.

Conclusion

Fosfomycin tromethamine is safe in preventing urinary tract infection and decreases the need for postoperative parenteral antibiotics in pregnant women who require lower urinary tract endoscopic procedures.
Scrotal reconstruction with pedicled gracilis muscle flap following Fournier’s gangrene: a case report and literature review
Authors: Ilori Oluwatosin Stephen , Onilede David. A. , Popoola Ademola. A. , Olatide Olorunnisola O. , Ugwuoke Chidi O.
Published: December 2021

Background

Fournier’s gangrene is an acute soft tissue necrotizing infection involving the perineum and the external genitalia which can result in a major loss of the scrotal wall with exposure of the testicles. Reconstruction of such major defect is quite challenging; the use of pedicled gracilis muscle flap helps to create an aesthetically acceptable scrotum with minimal donor site morbidity.

Case presentation

We described the case of a 60-year-old man with a large scrotal loss from Fournier’s gangrene following bladder outlet obstruction and perineal abscess. He had multiple debridement and reconstruction with pedicled left gracilis muscle flap with a good aesthetic and functional post-operative outcome. The major challenge encountered was the loss of the skin graft as a result of the retraction of the muscle flap due to too early ambulation; this can thus be avoided by adequate pre-operative counseling and enforcing bed rest.

Conclusions

The use of gracilis muscle flap in the reconstruction of large scrotal defect described in this report has the additional advantage of creating a pliable and soft feel like that of the original scrotum with minimal donor site morbidity.
A review on deep learning MRI reconstruction without fully sampled k-space
Authors: Zeng Gushan , Guo Yi , Zhan Jiaying , Wang Zi , Lai Zongying , Du Xiaofeng , Qu Xiaobo , Guo Di
Published: December 2021

Background

Magnetic resonance imaging (MRI) is an effective auxiliary diagnostic method in clinical medicine, but it has always suffered from the problem of long acquisition time. Compressed sensing and parallel imaging are two common techniques to accelerate MRI reconstruction. Recently, deep learning provides a new direction for MRI, while most of them require a large number of data pairs for training. However, there are many scenarios where fully sampled k-space data cannot be obtained, which will seriously hinder the application of supervised learning. Therefore, deep learning without fully sampled data is indispensable.

Main text

In this review, we first introduce the forward model of MRI as a classic inverse problem, and briefly discuss the connection of traditional iterative methods to deep learning. Next, we will explain how to train reconstruction network without fully sampled data from the perspective of obtaining prior information.

Conclusion

Although the reviewed methods are used for MRI reconstruction, they can also be extended to other areas where ground-truth is not available. Furthermore, we may anticipate that the combination of traditional methods and deep learning will produce better reconstruction results.
Cerebral small vessel disease, cardiovascular risk factors, and future walking speed in old age: a population-based cohort study
Authors: Heiland Emerald G. , Welmer Anna-Karin , Kalpouzos Grégoria , Laveskog Anna , Wang Rui , Qiu Chengxuan
Published: December 2021

Background

The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs).

Methods

This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up.

Results

Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient − 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed.

Conclusions

Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.
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

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

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

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

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

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

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

Background

Shrimp 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.

Methods

Mild 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.

Results

DAO/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.

Conclusion

Our 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

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

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

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.
Measuring sexual violence stigma in humanitarian contexts: assessment of scale psychometric properties and validity with female sexual violence survivors from Somalia and Syria
Authors: Murray Sarah M. , Lasater Molly E. , Guimond Marie-France , Poku Ohemaa , Musci Rashelle , Al-Fataftah Manal , Kasina Lilian , Lwambi Mercy , Salaimeh Asma , Falb Kathryn
Published: December 2021

Background

Valid measures of sexual violence stigma that can be readily incorporated into program monitoring and evaluation systems are needed to strengthen gender-based violence (GBV) services in humanitarian emergencies. This study sought to assess the psychometric properties, construct validity, and measurement invariance of sexual violence stigma scales among female Somali GBV survivors in Kenya and Syrian GBV survivors in Jordan to identify an abbreviated scale that could be used across humanitarian contexts.

Methods

We administered measures of sexual violence stigma to 209 female survivors of sexual violence aged 15 and older in Kenya and Jordan. Exploratory factor analysis was used to assess the underlying latent structure, and Item Response Theory was used to estimate item difficulty and discrimination parameters to guide efforts to shorten the scales. Differential item functioning (DIF) by site was assessed using Multiple Indicators, Multiple Causes models. Construct validity of the sexual violence stigma scales was assessed by estimating correlations with functional impairment, depression, and disability.

Results

The sexual violence stigma measure exhibited distinct factor structures among Somali and Syrian GBV survivors. Among Somali survivors, a two-factor model with separate felt (10 items) and enacted (4 items) stigma constructs was identified, with scales for both domains exhibiting good internal consistency (Cronbach’s alpha = 0.93 and 0.88, respectively). In Jordan, a single factor solution was uncovered for a 15-item stigma scale with good internal consistency (alpha = 0.86). The shortened core sexual stigma scale consisting of the 4 items that did not exhibit DIF had a Cronbach’s alpha of 0.82 in Kenya and 0.81 in Jordan. The felt stigma scale in Kenya, the full stigma scale in Jordan, and abbreviated core stigma scales in both countries were meaningfully correlated with depression, while correlations with functional impairment were weaker and inconsistent across scales.

Conclusions

An abbreviated core set of invariant perceived and internalized sexual violence stigma items demonstrated evidence of construct validity in two diverse settings. The ability of this measure to be efficiently administered as a part of routine program monitoring and evaluation activities, with the potential addition of items from a measurement bank to improve contextual relevance, can facilitate improvements in the delivery and quality of gender-based violence programs in humanitarian emergencies.
Which injured patients with moderate fibrinogen deficit need fibrinogen supplementation?
Authors: David Jean-Stephane , Lambert Aline , Taverna Xavier-Jean , Incagnoli Pascal , Geay-Baillat Marie-Odile , Vassal Olivia , Friggeri Arnaud , Inaba Kenji
Published: December 2021

Background

In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L−1, but some teams have suggested to use higher thresholds (fibrinogenemia < 2.0 g L−1 or FIBTEM clot amplitude at 5 min (A5) values < 11 mm). The goal of this study was to specify in patients with a moderate fibrinogen deficit (MFD) whether some admission characteristics would be associated with fibrinogen administration at 24 h.

Methods

Prospective analysis of retrospectively collected data from a trauma registry (01/2011–12/2019). MFD-C was defined by a fibrinogenemia 1.51–1.99 g L−1 or the corresponding FIBTEM-A5 values (MFD-A5) that were determined from linear regression and ROC curve analysis. Administration of fibrinogen were described according to the following admission parameters: shock index (SI) > 1, hemoglobin level < 110 g L−1 (HemoCue®), and base deficit > 5 mEq L−1. Data are expressed as count (%), median [IQR].

Results

1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19–36] vs. 24 [17–29]) and had more impaired vital signs (base deficit: 5.4 [3.6–7.8] vs. 3.8 [2.0–6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level < 1.5 g L−1 and < 2.0 g L−1, FIBTEM-A5 thresholds were 6 mm (sensitivity 85%, specificity 83%, AUC: 0.934) and 9 mm (sensitivity 84%, specificity 69%, AUC: 0.874), respectively. MFD-A5 values (185 (27%) patients) were defined as a FIBTEM-A5 between 7 and 9 mm. More than 50% of MFD-C patients presenting a SI > 1, a hemoglobin level < 110 g L−1, or a base deficit > 5.0 mEq L−1 received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06–1.82] for MFD-C, and 2.17 [1.48–3.19] for MFD-A5. Results were not modified after adjustment on the ISS.

Conclusions

We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.
The role of stromal immune microenvironment in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer
Authors: Niwińska Anna , Olszewski Wojciech P.
Published: December 2021

Aim

The first aim of the study was to compare the scores and types of stromal immune cells in 30 patients with primary DCIS and in the same patients after invasive breast recurrence in order to assess possible differences in both during tumor progression. The second aim was to evaluate possible differences in stromal cells of 30 patients with primary DCIS before progression and in the control group of 11 DCIS patients without recurrence during long-term follow-up.

Material and methods

Evaluation of tumor-infiltrating lymphocytes (TILs) and immunohistochemical stains for immune cell markers CD4, CD8, CD20, CD138, FOXP3, CD163 and TGF beta was performed on the stroma of primary DCIS before progression, invasive breast cancer of the same patients after progression and DCIS without progression.

Results

The comparison of stromal cells in 30 patients with initial DCIS and its invasive recurrence revealed an increased level of CD20 + immune cells (median score 5% vs. 17%, respectively, p < 0.001) and CD163 + cells (median score 1% vs. 5%, respectively, p < 0.001) in invasive breast cancer. The comparison of stromal cells in 30 patients with initial DCIS before recurrence and the control group of 11 patients with DCIS without recurrence showed statistically significant difference for CD138 + cells, which were more prevalent in patients with worse prognosis (median score 0 vs. 2%, respectively, p < 0.001). No similar relationship was found for the other tested cells as well as for TGF-beta.

Conclusions

CD138 + immune cells that were more prevalent in patients with a worse prognosis should be explored in further studies to confirm or exclude their role as a potential biological marker of DCIS invasive recurrence.
Carbon catabolite repression involves physical interaction of the transcription factor CRE1/CreA and the Tup1–Cyc8 complex in Penicillium oxalicum and Trichoderma reesei
Authors: Hu Yueyan , Li Mengxue , Liu Zhongjiao , Song Xin , Qu Yinbo , Qin Yuqi
Published: December 2021

Background

Cellulolytic enzyme production in filamentous fungi requires a release from carbon catabolite repression (CCR). The protein CRE1/CreA (CRE = catabolite responsive element) is a key transcription factor (TF) that is involved in CCR and represses cellulolytic gene expression. CRE1/CreA represents the functional equivalent of Mig1p, an important Saccharomyces cerevisiae TF in CCR that exerts its repressive effect by recruiting a corepressor complex Tup1p–Cyc8p. Although it is known from S. cerevisiae that CRE1/CreA might repress gene expression via interacting with the corepressor complex Tup1–Cyc8, this mechanism is unconfirmed in other filamentous fungi, since the physical interaction has not yet been verified in these organisms. The precise mechanism on how CRE1/CreA achieves transcriptional repression after DNA binding remains unknown.

Results

The results from tandem affinity purification and bimolecular fluorescence complementation revealed a direct physical interaction between the TF CRE1/CreA and the complex Tup1–Cyc8 in the nucleus of cellulolytic fungus Trichoderma reesei and Penicillium oxalicum. Both fungi have the ability to secrete a complex arsenal of enzymes to synergistically degrade lignocellulosic materials. In P. oxalicum, the protein PoCyc8, a subunit of complex Tup1–Cyc8, interacts directly with TF PoCreA and histone H3 lysine 36 (H3K36) methyltransferase PoSet2 in the nucleus. The di-methylation level of H3K36 in the promoter of prominent cellulolytic genes (cellobiohydrolase-encoding gene Pocbh1/cel7A and endoglucanase-encoding gene Poegl1/cel7B) is positively correlated with the expression levels of TF PoCreA. Since the methylation of H3K36 was also demonstrated to be a repression marker of cellulolytic gene expression, it appears feasible that the cellulolytic genes are repressed via PoCreA-Tup1–Cyc8-Set2-mediated transcriptional repression.

Conclusion

This study verifies the long-standing conjecture that the TF CRE1/CreA represses gene expression by interacting with the corepressor complex Tup1–Cyc8 in filamentous fungi. A reasonable explanation is proposed that PoCreA represses gene expression by recruiting complex PoTup1–Cyc8. Histone methyltransferase Set2, which methylates H3K36, is also involved in the regulatory network by interacting with PoCyc8. The findings contribute to the understanding of CCR mechanism in filamentous fungi and could aid in biotechnologically relevant enzyme production.
Creating a positive perception toward inclusive education with future-oriented thinking
Authors: Maeda Kaede , Hashimoto Hirofumi , Sato Kosuke
Published: December 2021

Objective

The purpose of this study was to examine the ways that encouraged people to develop positive attitudes and perceptions toward inclusive education. The Japanese special needs education system for students with disabilities has been shifting from a segregated model to a more inclusive form which is the major challenge facing educational systems around the world. While support for inclusive practices has grown rapidly in Japan, their implementation requires more attention. Considering these situations, in the current study, we experimentally manipulated future-oriented thinking and examined whether positive perceptions about inclusive education was enhanced if people acknowledged and realized that an inclusive society may improve the long-term welfare of not only people with disabilities but also people without disabilities or functional limitations.

Results

Our results partially confirmed that future-oriented thinking encouraged positive perceptions of inclusive education. It increased only when participants thought about the future employment of people with/without disabilities. No significant effects were found for the present orientation or control conditions.
Prazosin use in a patient with rare Neurobeachin gene deletion shows improvement in paranoid behavior: a case report
Authors: Cantwell Christina Y. , Fortman Jamie , Seegan Alexis
Published: December 2021

Background

Disruption of the Neurobeachin gene is a rare genetic mutation that has been implicated in the development of autism and enhanced long-term potentiation of the hippocampal CA1 region, causing a heightened conditioned fear response and impaired fear extinction. Prazosin, an alpha-1 receptor antagonist, has been used in patients with posttraumatic stress disorder to mitigate the increased alpha-1 activity involved in fear and startle responses. Here we report a case of a patient with a rare Neurobeachin gene deletion, who demonstrated marked and sustained improvement in paranoid behavior within days of prazosin initiation.

Case presentation

The patient is a 27-year-old White male with autism spectrum disorder, obsessive–compulsive disorder, and schizophrenia, with a chromosome 13q12 deletion including deletion of the Neurobeachin gene, who presented to the emergency department due to worsening functional status and profound weight loss as a result of only eating prepackaged foods. He had not showered or changed clothes in several months prior to presentation. He was hospitalized in the inpatient psychiatric unit for 2 months before prazosin was initiated. During that time, he demonstrated paranoia as evidenced by heightened sensitivity to doors opening, guarded interactions, and limited communication with providers and other patients. He also exhibited poor grooming habits, with aversion to showering, shaving, and changing clothes. Since initiating prazosin, he has demonstrated a brighter affect, initiates and maintains conversations, showers and changes clothes on a regular basis, and eats a variety of foods. At the time of this report, the patient was discharged to live in an apartment with a caregiver after a 7-month inpatient hospitalization.

Conclusions

Low-dose prazosin shows rapid and sustained improvement in paranoid behavior in a patient with a rare Neurobeachin gene deletion. Prazosin has a relatively favorable side effect profile with once-daily dosing and low cost. Prazosin may provide clinical improvement in patients with Neurobeachin gene deletions due to its theoretical attenuation in fear response through alpha-1 antagonism.
Facial onset sensory and motor neuropathy in a pain clinic outpatient: a case report
Authors: Hanawa Hiroki , Nagaoka Ryo , Fukuda Yuya , Akutsu Kazuya , Yamada Teppei , Hamaguchi Shinsuke
Published: December 2021

Background

Facial onset sensory and motor neuropathy is a very rare sensorimotor disorder characterized by facial onset and gradual progression, with approximately 100 cases reported worldwide in 2020. We report on our experience with a facial onset sensory and motor neuropathy case in our outpatient pain clinic.

Case presentation

A 71-year-old Japanese man with a previous diagnosis of trigeminal nerve palsy complained of facial paresthesia, cervical pain, and arm numbness. Cervical facet arthropathy was diagnosed initially, but neither pharmacotherapy nor nerve blocking alleviated his symptoms. We suspected bulbar palsy based on the presence of tongue fasciculation, which prompted referral to a neurologist. Based on a series of neurological examinations, facial onset sensory and motor neuropathy was ultimately diagnosed.

Conclusions

Pain clinicians must be mindful of rare diseases such as facial onset sensory and motor neuropathy; if they are unable to make a diagnosis, they should consult with other competent specialists.
Dynamic immune response characteristics of piglets infected with Actinobacillus pleuropneumoniae through omic
Authors: Zhu Rining , Jiang Hexiang , Wang Jun , Bao Chuntong , Liu Haiyao , Li Fengyang , Lei Liancheng
Published: December 2021

Porcine infectious pleuropneumonia is characterized by a high-rate of carriage and mixed infection with other pathogens. The host immune response induced by Actinobacillus pleuropneumoniae (APP) is the basis for elucidating pathogenesis and controlling disease. However, there is currently no comprehensive and dynamic data characterising the host immune response. In this study, piglets were infected with APP and differentially expressed proteins of bronchoalveolar lavage fluid (BALF) and peripheral serum were identified by iTRAQ-LC-MS/MS, and differentially expressed genes of peripheral blood mononuclear cells (PBMC) by RNA-seq. The results of the integrated analysis of serum, BALF and PBMC showed significant metabolism and local immune responses in BALF, the general immune response in PBMC mainly involves cytokines, while that in serum mainly involves biosynthesis, phagosome, and complement and coagulation cascades. Furthermore, immune responses in PBMCs and serum were rapid and maintained compared to the lung where metabolism and cell adhesion activities were enriched. Some innate immunity pathways of the cellular response to ROS, neutrophil mediated immunity, granulocyte activation and leukocyte cell-cell adhesion were identified as central points, connecting multiple signaling pathways to form an integrated large network. At 24 h post-infection, 14 molecules were up regulated in BALF, 10 of which were shared with PBMC, but at 120 h, 20 down-regulated molecules were identified in BALF, 11 of them still up- regulated in PBMC. We conclude that, the immune response in the lung is different from that in blood, but there is a similarity in response in PBMC and serum.