Liver fat volume fraction measurements based on multi-material decomposition algorithm in patients with nonalcoholic fatty liver disease: the influences of blood vessel, location, and iodine contrast.

BACKGROUND: In recent years, spectral CT-derived liver fat quantification method named multi-material decomposition (MMD) is playing an increasingly important role as an imaging biomarker of hepatic steatosis. However, there are various measurement ways with various results among different researches, and the impact of measurement methods on the research results is unknown. The aim of this study is to evaluate the reproducibility of liver fat volume fraction (FVF) using MMD algorithm in nonalcoholic fatty liver disease (NAFLD) patients when taking blood vessel, location, and iodine contrast into account during measurement. METHODS: This retrospective study was approved by the institutional ethics committee, and the requirement for informed consent was waived because of the retrospective nature of the study. 101 patients with NAFLD were enrolled in this study. Participants underwent non-contrast phase (NCP) and two-phase enhanced CT scanning (late arterial phase (LAP) and portal vein phase (PVP)) with spectral mode. Regions of interest (ROIs) were placed at right posterior lobe (RPL), right anterior lobe (RAL) and left lateral lobe (LLL) to obtain FVF values on liver fat images without and with the reference of enhanced CT images. The differences of FVF values measured under different conditions (ROI locations, with/without enhancement reference, NCP and enhanced phases) were compared. Friedman test was used to compare FVF values among three phases for each lobe, while the consistency of FVF values was assessed between each two phases using Bland-Altman analysis. RESULTS: Significant difference was found between FVF values obtained without and with the reference of enhanced CT images. There was no significant difference about FVF values obtained from NCP images under the reference of enhanced CT images between any two lobes or among three lobes. The FVF value increased after the contrast injection, and there were significant differences in the FVF values among three scanning phases. Poor consistencies of FVF values between each two phases were found in each lobe by Bland-Altman analysis. CONCLUSION: MMD algorithm quantifying hepatic fat was reproducible among different lobes, while was influenced by blood vessel and iodine contrast.

Measuring moral distress in health professionals using the MMD-HP-SPA scale.

BACKGROUND: Moral distress (MD) is the psychological damage caused when people are forced to witness or carry out actions which go against their fundamental moral values. The main objective was to evaluate the prevalence and predictive factors associated with MD among health professionals during the pandemic and to determine its causes. METHODS: A regional, observational and cross-sectional study in a sample of 566 professionals from the Public Health Service of Andalusia (68.7% female; 66.9% physicians) who completed the MMD-HP-SPA scale to determine the level of MD (0-432 points). Five dimensions were used: i) Health care; ii) Therapeutic obstinacy-futility, iii) Interpersonal relations of the Healthcare Team, iv) External pressure; v) Covering up of medical malpractice. RESULTS: The mean level of MD was 127.3 (SD=66.7; 95% CI 121.8-132.8), being higher in female (135 vs. 110.3; p<0.01), in nursing professionals (137.8 vs. 122; p<0.01) and in the community setting (136.2 vs. 118.3; p<0.001), with these variables showing statistical significance in the multiple linear regression model (p<0.001; r2=0.052). With similar results, the multiple logistic regression model showed being female was a higher risk factor (OR=2.27; 95% CI 1.5-3.4; p<0.001). 70% of the sources of MD belonged to the dimension "Health Care" and the cause "Having to attend to more patients than I can safely attend to" obtained the highest average value (Mean=9.8; SD=4.9). CONCLUSIONS: Female, nursing professionals, and those from the community setting presented a higher risk of MD. The healthcare model needs to implement an ethical approach to public health issues to alleviate MD among its professionals.

Disbelief, Distress, & Distrust: Trending Institution Related Emotional Distress During COVID-19.

The COVID-19 pandemic had an unprecedented impact on the well-being of individuals working in the healthcare sector. Though many studies exist that focus on physician and nurse well-being, few have specifically identified stressors that affect professionals working within the end-of-life interdisciplinary team. The primary objective of this study was to expand research on moral distress and clinician well-being to include healthcare professionals working with patients with chronic and life-limiting illnesses during the COVID-19 pandemic. A survey approach was used with 110 professionals working within one hospital network's palliative and hospice team to identify key indicators of moral distress (using the MMD-HP scale) and professional well-being during the pandemic. Quantitative and qualitative analysis was completed to determine themes related to moral distress and professional well-being. Numerous themes were identified, including the importance of caseload, general support, team support, management, and professional flexibility. Additional end-of-life themes were identified, including the impact of death, lack of personal protective equipment, fear of transmitting the virus, COVID disbelief, and the inability of clinicians and/or family to be with patients in person. From the experience participants had during COVID-19, four areas of change were identified: professional resilience, management/ethics support, professional development, and physical and emotional safety.

Defining migraine days, based on longitudinal E-diary data.

BACKGROUND: There is a need for standardization of the definition of a migraine day for clinical and research purposes. METHODS: We prospectively compared different definitions of a migraine day with E-diary data of n = 1494 patients with migraine. We used a baseline definition based on migraine characteristics with a duration of ≥4 hours OR triptan intake (independently from its effect) OR (visual) aura lasting 5-60 minutes. RESULTS: Of all migraine days defined by triptan intake only, 66.2% had a duration <4 hours. Adjusting the headache duration criterion to ≥30 minutes led to a decrease in days defined by triptan intake only and resulted in a 5.4% increase in total migraine days (equals 0.45 migraine day increase in monthly migraine days). These additional migraine days had a median duration of 2.5 hours. CONCLUSION: We propose to define a migraine day as follows: 1) (a) headache duration ≥30 minutes; (b) matching ≥2 of four characteristics: unilateral, pulsating, moderate to severe pain, aggravation by or causing avoidance of routine physical activity; and (c) during headache ≥1 of the following: nausea and/or vomiting, photophobia and phonophobia or 2) (visual) aura duration 5-60 minutes or 3) a day with headache for which acute migraine-specific medication is used irrespective of its effect.

Impact of medication therapy management (MTM) service model on multi-morbidity (MMD) patients with hypertension: a pilot RCT.

BACKGROUND: This study explored the impact of MTM service on MMD patients with hypertension. METHODS: A total of 120 MMD inpatients from September to November 2019 were received and randomly divided into intervention group and control group. General services for noninfectious chronic diseases were given to the control group, while a standard MTM service was given to the intervention group. Patients' blood pressure, EQ-5D utility value, readmission rate, drug-related problems, and average daily medication therapy cost were compared between the two groups and within the groups. This was done at the initial admission phase and in the first, third, sixth, and twelfth months after discharge. RESULTS: The intervention group had significantly lower blood pressure and average daily medication therapy cost 12 months after discharge compared to the control group (systolic blood pressure: P = 0.023, diastolic blood pressure: P < 0.001, average daily medication therapy cost: P = 0.049); the number of DRPs decreased in both groups 12 months after discharge; the number of DRPs solved in the intervention group in the third, sixth and twelfth months after discharge were statistically higher compared with that in the control group (P = 0.013, P = 0.012, P = 0.001); there was no significant difference in the EQ-5D utility value and readmission rate between the two groups (P > 0.05). CONCLUSIONS: MTM implementation in MMD patients can improve health outcomes and reduce healthcare-related costs among MMD patients. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2200065111, date of registration: October 28, 2022.

Learning spatiotemporal features of DSA using 3D CNN and BiConvGRU for ischemic moyamoya disease detection.

BACKGROUND: Moyamoya disease (MMD) is a serious intracranial cerebrovascular disease. Cerebral hemorrhage caused by MMD will bring life risk to patients. Therefore, MMD detection is of great significance in the prevention of cerebral hemorrhage. In order to improve the accuracy of digital subtraction angiography (DSA) in the diagnosis of ischemic MMD, in this paper, a deep network architecture combined with 3D convolutional neural network (3D CNN) and bidirectional convolutional gated recurrent unit (BiConvGRU) is proposed to learn the spatiotemporal features for ischemic MMD detection. METHODS: Firstly, 2D convolutional neural network (2D CNN) is utilized to extract spatial features for each frame of DSA. Secondly, the long-term spatiotemporal features of DSA sequence are extracted by BiConvGRU. Thirdly, the short-term spatiotemporal features of DSA are further extracted by 3D convolutional neural network (3D CNN). In addition, different features are extracted when gray images and optical flow images pass through the network, and multiple features are extracted by features fusion. Finally, the fused features are utilized to classify. RESULTS: The proposed method was quantitatively evaluated on a data sets of 630 cases. The experimental results showed a detection accuracy of 0.9788, sensitivity and specificity were 0.9780 and 0.9796, respectively, and area under curve (AUC) was 0.9856. Compared with other methods, we can get the highest accuracy and AUC. CONCLUSIONS: The experimental results show that the proposed method is stable and reliable for ischemic MMD detection, which provides an option for doctors to accurately diagnose ischemic MMD.

Different phenotypes of moyamoya disease in a Chinese familial case involving heterozygous c.14429G>a variant in RNF213.

PURPOSE: Moyamoya disease (MMD) is an uncommon chronic and occlusive cerebrovascular disorder involving the development of abnormal collateral vessels. This report aimed to describe a Chinese familial case with a rare variant in the RNF213 gene. METHODS: The present report presents a rare familial case of MMD involving a heterozygous c.14429G>A variant in RNF213 and exhibiting different phenotypes. RESULTS: A 3-year-old Chinese boy and his 10-year-old sister diagnosed severe bilateral MMD, while their mother was diagnosed asymptomatic bilateral MMD, based on the imaging results of magnetic resonance angiography (MRA). The boy mainly showed numbness at left hand accompanied by dysphasia and dyskinesia, while his sister had complex symptoms including dysphasia, dyskinesia at both hands and fatigue of limbs. Muscle force was ranked as left (upper limb/lower limb: 4/3) and right (upper limb/lower limb: 3/4). Genetic testing indicated a heterozygous c.14429G>A variant in RNF213 in 3 patients. The 3 patients shared the same amino acid substitution of p.Arg4810Lys caused by c.14429G>A. The father of two children also underwent genetic testing for RNF213 and MRI examination but found normal in all indices. CONCLUSIONS: Genetic testing for RNF213 is suggested for MMD screening towards family members, and c.14576G>A variant is identified as an important pathogenic mutation with family heritability.

Moya Moya Disease: A rare disease with a common presenting symptom in a chronic kidney disease patient.

Moya Moya Disease (MDD) is a rare cerebrovascular pathology. It is non atherosclerotic cerebrovascular disease characterized by bilateral internal carotid stenosis or occlusion, and abnormal vascular network at the base of the brain. Here we report a case of young female who presented in emergency with complaints of jerky movements of limbs for six months and history of recently developed unusual high blood pressure which was followed by uremic symptoms. Her workup revealed severe renal dysfunction required kidney replacement therapy (KRT) i.e., hemodialysis. During hospital stay her mental status deteriorated with a drop in GCS. Brain imaging performed and she found to have MMD. Her clinical course continued to deteriorate despite of extensive work up and aggressive management, she died eventually.

Trade-off between conservation of biological variation and batch effect removal in deep generative modeling for single-cell transcriptomics.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) technology has contributed significantly to diverse research areas in biology, from cancer to development. Since scRNA-seq data is high-dimensional, a common strategy is to learn low-dimensional latent representations better to understand overall structure in the data. In this work, we build upon scVI, a powerful deep generative model which can learn biologically meaningful latent representations, but which has limited explicit control of batch effects. Rather than prioritizing batch effect removal over conservation of biological variation, or vice versa, our goal is to provide a bird's eye view of the trade-offs between these two conflicting objectives. Specifically, using the well established concept of Pareto front from economics and engineering, we seek to learn the entire trade-off curve between conservation of biological variation and removal of batch effects. RESULTS: A multi-objective optimisation technique known as Pareto multi-task learning (Pareto MTL) is used to obtain the Pareto front between conservation of biological variation and batch effect removal. Our results indicate Pareto MTL can obtain a better Pareto front than the naive scalarization approach typically encountered in the literature. In addition, we propose to measure batch effect by applying a neural-network based estimator called Mutual Information Neural Estimation (MINE) and show benefits over the more standard maximum mean discrepancy measure. CONCLUSION: The Pareto front between conservation of biological variation and batch effect removal is a valuable tool for researchers in computational biology. Our results demonstrate the efficacy of applying Pareto MTL to estimate the Pareto front in conjunction with applying MINE to measure the batch effect.

Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research.

OBJECTIVE: To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels. METHODS: The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction. RESULTS: In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012-0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132-0.926]). CONCLUSIONS: Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Validation of the Berlin Grading System for moyamoya angiopathy with the use of [15O]H2O PET.

The Berlin Grading System assesses clinical severity of moyamoya angiopathy (MMA) by combining MRI, DSA, and cerebrovascular reserve capacity (CVRC). Our aim was to validate this grading system using [15O]H2O PET for CVRC. We retrospectively identified bilateral MMA patients who underwent [15O]H2O PET examination and were treated surgically at our department. Each hemisphere was classified using the Suzuki and Berlin Grading System. Preoperative symptoms and perioperative ischemias were collected, and a logistic regression analysis was performed. A total of 100 hemispheres in 50 MMA patients (36 women, 14 men) were included. Using the Berlin Grading System, 2 (2.8%) of 71 symptomatic hemispheres were categorized as grade I, 14 (19.7%) as grade II, and 55 (77.5%) as grade III. The 29 asymptomatic hemispheres were characterized as grade I in 7 (24.1%) hemispheres, grade II in 12 (41.4%), and grade III in 10 (34.5%) hemispheres. Berlin grades were independent factors for identifying hemispheres as symptomatic and higher grades correlated with increasing proportion of symptomatic hemispheres (p < 0.01). The Suzuki grading did not correlate with preoperative symptoms (p = 0.26). Perioperative ischemic complications occurred in 8 of 88 operated hemispheres. Overall, complications did not occur in any of the grade I hemispheres, but in 9.1% (n = 2 of 22) and 9.8% (n = 6 of 61) of grade II and III hemispheres, respectively. In this study, we validated the Berlin Grading System with the use of [15O]H2O PET for CVRC as it could stratify preoperative symptomatology. Furthermore, we highlighted its relevance for predicting perioperative ischemic complications.

Method for Predicting RUL of Rolling Bearings under Different Operating Conditions Based on Transfer Learning and Few Labeled Data.

As industrial development increases, electric machine systems are more widely used in industrial production. Rolling bearings play a key role in machine systems and so the prevention of faults in rolling bearings is more important than ever before. Recently, with the development of artificial intelligence, neural networks have been used to monitor the remaining useful life of rolling bearings. However, there are two problems with this technique. First, a network trained by data for a single operating condition (source domain) cannot predict the remaining useful life of bearings under a different operating condition (target domain), such as a different load or speed. Second, a large number of labeled data are needed for network training, but the acquisition of labeled data for different operating conditions is a challenging task. To address these problems, this paper proposes a domain-adaptive adversarial network, in which a transfer learning strategy and maximum mean discrepancy algorithm are used for network optimization, so that remaining useful life can be predicted without labeled data in target domain training. Our results confirm that a model trained by source domain data alone cannot predict the remaining useful life of bearings under different conditions, but the domain-adaptive adversarial network can accurately predict remaining useful life for varying operating conditions. The method proposed also exhibits good performance even if there are noises in the signals.

Estimating the cost and efficiency gain of rolling out a multi-month dispensing programme for antiretroviral treatment in Tanzania.

Background: Globally, efforts to curtail the HIV pandemic are growing. The Joint United Nations Programme on HIV and AIDS (UNAIDS) and partners set the 95-95-95 targets to be achieved by 2025. Tanzania's ongoing transition from single-month ARV to longer multi-month dispensing (MMD) involves significant planning and shifts in existing resources, including health commodities, clinical staff and storage space. This study aimed at evaluating the costs and efficiency gains of rolling out MMD compared to the prior monthly dispending (MD) standard of care before the new guidelines.Methods: The analysis employed a health provider perspective utilising prior costing data collected to estimate cost of treatment for HIV/AIDS, including salaries, laboratory costs, antiretroviral drugs, other supplies and overhead costs. The projections were run from 2018 to 2030 using the Spectrum package for Tanzania.Results: Our model estimated that total treatment cost without MMD (including salaries, laboratory costs, antiretroviral drugs, other supplies, and overhead costs) is estimated to rise from USD 189 million in 2018 to USD 244 million in 2030. The introduction of a six-month MMD would lead to the total annual facility-based treatment costs being reduced to USD 205 million in 2030. When comparing MD to a six-month MMD, the total savings over the 13-year period would be USD 425 million. The introduction of six-month MMD for stable patients would reduce the average cost from USD 180 to USD 156 per patient per year if stable patients were only required to make six-monthly visit.Conclusions: The introduction of differentiated service delivery models (DSDMs) and MMD is already contributing to significant cost savings for Tanzania and will continue to do so as the country puts more stable patients on MMD. The potential gains from MMD implantation could further be harnessed if retention of treatment and viral suppression monitoring are prioritised.

Bi-allelic expression of the RyR1 p.A4329D mutation decreases muscle strength in slow-twitch muscles in mice.

Mutations in the ryanodine receptor 1 (RYR1) gene are associated with several human congenital myopathies, including the dominantly inherited central core disease and exercise-induced rhabdomyolysis, and the more severe recessive phenotypes, including multiminicore disease, centronuclear myopathy, and congenital fiber type disproportion. Within the latter group, those carrying a hypomorphic mutation in one allele and a missense mutation in the other are the most severely affected. Because of nonsense-mediated decay, most hypomorphic alleles are not expressed, resulting in homozygous expression of the missense mutation allele. This should result in 50% reduced expression of the ryanodine receptor in skeletal muscle, but its observed content is even lower. To study in more detail the biochemistry and pathophysiology of recessive RYR1 myopathies, here we investigated a mouse model we recently generated by analyzing the effect of bi-allelic versus mono-allelic expression of the RyR1 p.A4329D mutation. Our results revealed that the expression of two alleles carrying the same mutation or of one allele with the mutation in combination with a hypomorphic allele does not result in functionally equal outcomes and impacts skeletal muscles differently. In particular, the bi-allelic RyR1 p.A4329D mutation caused a milder phenotype than its mono-allelic expression, leading to changes in the biochemical properties and physiological function only of slow-twitch muscles and largely sparing fast-twitch muscles. In summary, bi-allelic expression of the RyR1 p.A4329D mutation phenotypically differs from mono-allelic expression of this mutation in a compound heterozygous carrier.

Factors associated with an interruption in treatment of people living with HIV in USAID-supported states in Nigeria: a retrospective study from 2000-2020.

BACKGROUND: Patient interruption of antiretroviral therapy (ART) continues to limit HIV programs' progress toward epidemic control. Multiple factors have been associated with client interruption in treatment (IIT)- including age, gender, CD4 count, and education level. In this paper, we explore the factors associated with IIT in people living with HIV (PLHIV) in United States Agency for International Development (USAID)-supported facilities under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. METHODS: We conducted cross-sectional analyses on data obtained from Nigeria's National Data Repository (NDR), representing a summarized record of 573 630 ART clients that received care at 484 PEPFAR/USAID-supported facilities in 16 states from 2000-2020. IIT was defined as no clinical contact for 28 days or more after the last expected clinical contact. Univariate and multivariate logistic regression models were computed to explore the factors associated with IIT. The variables included in the analysis were sex, age group, zone, facility level, regimen line, multi-month dispensing (MMD), and viral load category. RESULTS: Of the 573 630 clients analysed in this study, 32% have been recorded as having interrupted treatment. Of the clients investigated, 66% were female (32% had interrupted treatment), 39% were aged 25-34 at their last ART pick-up date (with 32% of them interrupted treatment), 59% received care at secondary level facilities (37% interrupted treatment) and 38% were last receiving between three- to five-month MMD (with 10% of these interrupted treatment). Those less likely to interrupt ART were males (aOR = 0.91), clients on six-month MMD (aOR = 0.01), adults on 2nd line regimen (aOR = 0.09), and paediatrics on salvage regimen (aOR = 0.02). Clients most likely to interrupt ART were located in the South West Zone (aOR = 1.99), received treatment at a tertiary level (aOR = 12.34) or secondary level facilities (aOR = 4.01), and had no viral load (VL) on record (aOR =10.02). Age group was not significantly associated with IIT. CONCLUSIONS: Sex, zone, facility level, regimen line, MMD, and VL were significantly associated with IIT. MMD of three months and longer (especially six months) had better retention on ART than those on shorter MMD. Not having a VL on record was associated with a considerable risk of IIT.

Applying MMD Data Mining to Match Network Traffic for Stepping-Stone Intrusion Detection.

A long interactive TCP connection chain has been widely used by attackers to launch their attacks and thus avoid detection. The longer a connection chain, the higher the probability the chain is exploited by attackers. Round-trip Time (RTT) can represent the length of a connection chain. In order to obtain the RTTs from the sniffed Send and Echo packets in a connection chain, matching the Sends and Echoes is required. In this paper, we first model a network traffic as the collection of RTTs and present the rationale of using the RTTs of a connection chain to represent the length of the chain. Second, we propose applying MMD data mining algorithm to match TCP Send and Echo packets collected from a connection. We found that the MMD data mining packet-matching algorithm outperforms all the existing packet-matching algorithms in terms of packet-matching rate including sequence number-based algorithm, Yang's approach, Step-function, Packet-matching conservative algorithm and packet-matching greedy algorithm. The experimental results from our local area networks showed that the packet-matching accuracy of the MMD algorithm is 100%. The average packet-matching rate of the MMD algorithm obtained from the experiments conducted under the Internet context can reach around 94%. The MMD data mining packet-matching algorithm can fix the issue of low packet-matching rate faced by all the existing packet-matching algorithms including the state-of-the-art algorithm. It is applicable to network-based stepping-stone intrusion detection.

C2DAN: An Improved Deep Adaptation Network with Domain Confusion and Classifier Adaptation.

Deep neural networks have been successfully applied in domain adaptation which uses the labeled data of source domain to supplement useful information for target domain. Deep Adaptation Network (DAN) is one of these efficient frameworks, it utilizes Multi-Kernel Maximum Mean Discrepancy (MK-MMD) to align the feature distribution in a reproducing kernel Hilbert space. However, DAN does not perform very well in feature level transfer, and the assumption that source and target domain share classifiers is too strict in different adaptation scenarios. In this paper, we further improve the adaptability of DAN by incorporating Domain Confusion (DC) and Classifier Adaptation (CA). To achieve this, we propose a novel domain adaptation method named C2DAN. Our approach first enables Domain Confusion (DC) by using a domain discriminator for adversarial training. For Classifier Adaptation (CA), a residual block is added to the source domain classifier in order to learn the difference between source classifier and target classifier. Beyond validating our framework on the standard domain adaptation dataset office-31, we also introduce and evaluate on the Comprehensive Cars (CompCars) dataset, and the experiment results demonstrate the effectiveness of the proposed framework C2DAN.

Postoperative Functional Outcomes and Prognostic Factors in Two Types of Adult Moyamoya Diseases.

BACKGROUND: To determine the functional outcomes in each period for adult ischemic and hemorrhagic Moyamoya disease (MMD) patients and identify prognostic factors. METHODS: The current retrospective study reviewed consecutive adult MMD patients surgically treated from January 2012 to June 2017. Perioperative clinical data were collected and follow-up was conducted via telephone interviews. Functional outcomes and prognostic factors were analyzed. RESULTS: A total of 219 ischemic MMD patients (268 hemispheres) and 157 hemorrhagic patients (193 hemispheres) were included. The median follow-up time was 18 months (3-69 months). MMD type had no significant effect on the modified Rankin Scale(mRS) score at discharge. Perioperative complications (P = 0.004) and the mRS score at baseline (P < 0.001) were risk factors correlated with the short-term functional outcomes in both groups, while diabetes mellitus (DM, P = 0.022) also played a role in the ischemic group. During the follow-up period, functional outcomes obviously improved in both groups, but two groups showed nonproportional cumulative curves for favorable functional outcomes (log-rank test, P = 0.483). Stroke recurrence (P < 0.001) and mRS at discharge (P < 0.001) were common factors related with long-term functional outcomes in two types of MMD patients. Particularly, female patients with ischemic MMD were more likely to have higher mRS scores (P = 0.028) and Suzuki stage was positively associated with long-term functional outcomes in hemorrhagic group (P = 0.044). CONCLUSIONS: MMD type had no significant effect on prognosis while both types of MMD patients showed overall significant improvements in functional outcomes after surgery. Different types of MMD patients have distinct prognostic factors for short-term and long-term functional outcomes.

Mutation in a PHD-finger protein MS4 causes male sterility in soybean.

BACKGROUND: Male sterility has tremendous scientific and economic importance in hybrid seed production. Identification and characterization of a stable male sterility gene will be highly beneficial for making hybrid seed production economically feasible. In soybean, eleven male-sterile, female-fertile mutant lines (ms1, ms2, ms3, ms4, ms5, ms6, ms7, ms8, ms9, msMOS, and msp) have been identified and mapped onto various soybean chromosomes, however the causal genes responsible for male sterility are not isolated. The objective of this study was to identify and functionally characterize the gene responsible for the male sterility in the ms4 mutant. RESULTS: The ms4 locus was fine mapped to a 216 kb region, which contains 23 protein-coding genes including Glyma.02G243200, an ortholog of Arabidopsis MALE MEIOCYTE DEATH 1 (MMD1), which is a Plant Homeodomain (PHD) protein involved in male fertility. Isolation and sequencing of Glyma.02G243200 from the ms4 mutant line showed a single base insertion in the 3rd exon causing a premature stop codon resulting in truncated protein production. Phylogenetic analysis showed presence of a homolog protein (MS4_homolog) encoded by the Glyma.14G212300 gene. Both proteins were clustered within legume-specific clade of the phylogenetic tree and were likely the result of segmental duplication during the paleoploidization events in soybean. The comparative expression analysis of Ms4 and Ms4_homologs across the soybean developmental and reproductive stages showed significantly higher expression of Ms4 in early flowering (flower bud differentiation) stage than its homolog. The functional complementation of Arabidopsis mmd1 mutant with the soybean Ms4 gene produced normal stamens, successful tetrad formation, fertile pollens and viable seeds, whereas the Ms4_homolog was not able to restore male fertility. CONCLUSIONS: Overall, this is the first report, where map based cloning approach was employed to isolate and characterize a gene responsible for the male-sterile phenotype in soybean. Characterization of male sterility genes may facilitate the establishment of a stable male sterility system, highly desired for the viability of hybrid seed production in soybean. Additionally, translational genomics and genome editing technologies can be utilized to generate new male-sterile lines in other plant species.

Wound healing complications after revascularization for moyamoya vasculopathy with reference to different skin incisions.

OBJECTIVEMoyamoya vasculopathy (MMV) is a steno-occlusive cerebrovascular disease that can be treated by a surgical revascularization. All the revascularization techniques influence the blood supply of the scalp, with a risk for wound healing disorders. The authors' aim was to analyze the wound healing process in the patients who underwent a direct or combined bypass surgery with a focus on different skin incisions.METHODSThe authors retrospectively identified all the patients with MMV who were treated surgically in their institution. Subsequently, they analyzed demographic data, clinical symptoms, surgical treatment, and detailed history of complications. Based on the evolution of their surgical techniques and the revascularization strategy to be used, the authors applied the following skin incisions: linear incision, curved incision, incomplete Y incision, and complete Y incision. Group comparisons regarding wound healing disorders were performed with significance testing using Fisher's exact test.RESULTSThe authors identified 172 patients with MMV (61.6% moyamoya disease, 7% unilateral moyamoya disease, 29.7% moyamoya syndrome, and 1.7% unilateral moyamoya syndrome), of whom 124 underwent bilateral operations. One-quarter of the patients were juveniles. A total of 236 hemispheres were included in the analysis, of which 27.9% were treated by a combined procedure with encephalomyosynangiosis. Overall, 5.1% major and 1.7% minor wound complications occurred. The overall wound complication rate was lower in direct revascularization compared to combined revascularization (3% vs 15.2%). The lowest incidence of wound healing disorders was found in the linear incision group for the parietal superficial temporal artery branch (1.6%), followed by the incomplete Y incision group for the frontal branch of the superficial temporal artery (3.8%) in the direct bypass group. In the combined revascularization cohort, major or minor wound disorders appeared in 14.3% and 4.8%, respectively, in the complete Y incision group and in 4.2% (for both major and minor) in the curved incision group. The complete Y incision caused significantly more wound healing disorders compared to the remaining incision types (17.1% vs 3.1%, p = 0.007).CONCLUSIONSWound healing disorders are one of the major complications of revascularization surgery. Their incidence depends on the revascularization strategy and skin incision applied, with a complete Y incision giving the worst results.