Miracle-dz/UniFAR-FTUs huggingface dataset:
Deciphering the Regulation of the Mannitol Operon Paves the Way for Efficient Production of Mannitol in Lactococcus lactis

Lactococcus lactis is the most studied species of the lactic acid bacteria, and it is widely used in various food fermentations. To date, there have been several attempts to persuade L. lactis to produce mannitol, a sugar alcohol with important therapeutic and food applications. ABSTRACT Lactococcus lactis has great potential for high-yield production of mannitol, which has not yet been fully realized. In this study, we characterize how the mannitol genes in L. lactis are organized and regulated and use this information to establish efficient mannitol production. Although the organization of the mannitol genes in L. lactis was similar to that in other Gram-positive bacteria, mtlF and mtlD, encoding the enzyme IIA component (EIIAmtl) of the mannitol phosphotransferase system (PTS) and the mannitol-1-phosphate dehydrogenase, respectively, were separated by a transcriptional terminator, and the mannitol genes were found to be organized in two transcriptional units: an operon comprising mtlA, encoding the enzyme IIBC component (EIIBCmtl) of the mannitol PTS, mtlR, encoding a transcriptional activator, and mtlF, as well as a separately expressed mtlD gene. The promoters driving expression of the two transcriptional units were somewhat similar, and both contained predicted catabolite responsive element (cre) genes. The presence of carbon catabolite repression was demonstrated and was shown to be relieved in stationary-phase cells. The transcriptional activator MtlR (mtlR), in some Gram-positive bacteria, is repressed by phosphorylation by EIIAmtl, and when we knocked out mtlF, we indeed observed enhanced expression from the two promoters, which indicated that this mechanism was in place. Finally, by overexpressing the mtlD gene and using stationary-phase cells as biocatalysts, we attained 10.1 g/liter mannitol with a 55% yield, which, to the best of our knowledge, is the highest titer ever reported for L. lactis. Summing up, the results of our study should be useful for improving the mannitol-producing capacity of this important industrial organism. IMPORTANCE Lactococcus lactis is the most studied species of the lactic acid bacteria, and it is widely used in various food fermentations. To date, there have been several attempts to persuade L. lactis to produce mannitol, a sugar alcohol with important therapeutic and food applications. Until now, to achieve mannitol production in L. lactis with significant titer and yield, it has been necessary to introduce and express foreign genes, which precludes the use of such strains in foods, due to their recombinant status. In this study, we systematically characterize how the mannitol genes in L. lactis are regulated and demonstrate how this impacts mannitol production capability. We harnessed this information and managed to establish efficient mannitol production without introducing foreign genes.
Impact of clinicopathological variables on laparoscopic hysterectomy complications, a tertiary center experience.

OBJECTIVES To analyze intraoperative and postoperative complications according to Clavian-Dindo Classification (CDC) and evaluate the influence of clinicopathological features on the feasibility and safety of total laparoscopic hysterectomy (TLH) in patients that underwent surgery in a tertiary center. MATERIAL AND METHODS We retrospectively reviewed the database of 469 patients that underwent surgery for patients who underwent extra facial TLH from 2013 to 2020. RESULTS A total of 86 (18.3%) peri-postoperative complications were observed. The incidence of intraoperative complications was 2% (n = 10). The overall conversion rate to open surgery was 1.9% (n = 9). A total of 76 postoperative complications were observed in 61 patients (14.3%). The incidence of minor (Grade I [n = 16, 3.4%] and II [n = 42, 8.9%]) and major complications (Grade III [n = 15, 3.2%], IV [n = 2, 0.4%] and V [n = 1, 0.2 %]) were 12.3% and 3.8%, respectively. A higher BMI and performing surgery at the first step of learning are found to be associated with intraoperative and postoperative complications (p < 0.05). Postoperative complications related to having a history of the cesarean section, additional comorbidities, and uterine weight ≥ 300 g (p < 0.05). CONCLUSIONS The implementation of TLH by experienced surgeons appears to have remarkable advantages over open surgery. However, the risk factor for complications should be taken into account by surgeons in the learning curve in selecting the appropriate patient for surgery.
Why and how the work of Motor Neurone Disease Associations matters before and during bereavement: a consumer perspective

Background: Studies on the experiences of consumers with Motor Neurone Disease Associations at end of life and bereavement are lacking, and their role and capability within the broader sectors of health and disability are unknown. Objectives: To ascertain the experiences and views of bereaved motor neurone disease caregivers with Motor Neurone Disease Associations about service gaps and needed improvements before and during bereavement and to propose a model of care that fits with consumer preferences and where Motor Neurone Disease Associations are effective enablers of care. Methods: A national bereavement survey was facilitated in 2019 by all Motor Neurone Disease Associations in Australia. A total of 363 respondents completed the section on support provided by Motor Neurone Disease Associations. A mixed-method design was used. Results: Respondents were generally positive about support received before bereavement (73-76%), except for emotional support (55%). Positive experiences related to the following: information, equipment advice/provision, advocacy/linking to services, showing empathy/understanding, personal contact and peer social support. Negative experiences included lack of continuity in case management and contact, perceived lack of competence or training, lack of emotional support and a lack of access to motor neurone disease services in rural areas. Suggested improvements were as follows: more contact and compassion at end of life and postdeath; better preparation for end of life; option of discussing euthanasia; providing referrals and links for counseling; access to caregiver support groups and peer interaction; provision of a genuine continuum of care rather than postdeath abandonment; guidance regarding postdeath practicalities; and more access to bereavement support in rural areas. Conclusion: This study provides consumer perspectives on driving new or improved initiatives by Motor Neurone Disease Associations and the need for a national standardised approach to training and service delivery, based on research evidence. A public health approach to motor neurone disease end-of-life care, of international applicability, is proposed to address the needs and preferences of motor neurone disease consumers, while supporting the capability of Motor Neurone Disease Associations within a multidisciplinary workforce to deliver that care.
Effectiveness and acceptability of brief psychoeducational interventions after potentially traumatic events: A systematic review

ABSTRACT Background: Experiencing a potentially traumatic event can put individuals at risk for both short-term and long-term mental health problems. While many psychological interventions exist for those who have experienced potentially traumatic events, there remains controversy about the best ways to support them. Objective: This review explores the effect of brief psychoeducational interventions after potentially traumatic experiences on adult recipients’ mental health, attitudes towards mental health, and trauma-related knowledge, as well as the perceived acceptability of psychoeducation. Methods: Four electronic databases were searched for relevant published literature. Results: Ten papers were included in the review. There was no evidence that psychoeducation was any more effective in terms of reducing mental health symptoms than other interventions or no intervention at all. There was some evidence that psychoeducation improved attitudes towards and knowledge of mental health immediately post-intervention; one study examined whether these improvements were sustained over the long term and found that they were not. However, psychoeducation was generally highly regarded by participants. Conclusions: This review did not find sufficient evidence to support routine use of brief psychoeducation as a stand-alone intervention.
Identification of microRNAs and gene regulatory networks in cleft lip common in humans and mice

Abstract The etiology of cleft lip with/without cleft palate (CL/P), one of the most frequent craniofacial birth defects worldwide, is complicated by contributions of both genetic and environmental factors. Understanding the etiology of these conditions is essential for developing preventive strategies. This study thus aims to identify regulatory networks of microRNAs (miRNAs), transcriptional factors (TFs) and non-TF genes associated with cleft lip (CL) that are conserved in humans and mice. Notably, we found that miR-27b, miR-133b, miR-205, miR-376b and miR-376c were involved in the regulation of CL-associated gene expression in both humans and mice. Among the candidate miRNAs, the overexpression of miR-27b, miR-133b and miR-205, but not miR-376b and miR-376c, significantly inhibited cell proliferation through suppression of CL-associated genes (miR-27b suppressed PAX9 and RARA; miR-133b suppressed FGFR1, PAX7, and SUMO1; and miR-205 suppressed PAX9 and RARA) in cultured human and mouse lip mesenchymal cells. Taken together, our results suggest that elevated expression of miR-27b, miR-133b and miR-205 may play a crucial role in CL through the suppression of genes associated with CL.
Discussion of “Improving precision and power in randomized trials for COVID‐19 treatments using covariate adjustment, for binary, ordinal, and time‐to‐event outcomes”

We congratulate the authors on a timely paper on covariate adjustment for COVID-19 treatment trials. It clearly demonstrates the great potential of leveraging covariates in increasing precision and power for randomized trials. Despite great advance in theory and methods, covariate adjustment is still underused in practice. This is partly due to that many practitioners remain skeptical of its usefulness or have other concerns. Some people think adjusted estimator estimates the conditional, as opposed to the desired marginal, treatment effect. This thought is naturally influenced by the traditional adjustment method where one directly models outcomes as a function of treatment and covariates. Perhaps the biggest obstacle to leveraging covariate is the concern about model misspecification. People may think that the validity of inference and/or improvement in efficiency rely on the assumption of correct modeling. Benkeser et al. (2020) alleviate these concerns through intuitive explanations and convincing empirical evidences. To further elucidate misunderstandings, we elaborate the key points from a theoretical point of view and discuss issues from a practical point of view.
A Combustion Test Facility for Testing Low NOx Combustion Systems

Cheng Power Systems has designed and built an atmospheric pressure combustion test facility for gas turbines, which has the capability of testing the full size combustion systems of large gas turbines at atmospheric pressure while maintaining the adiabatic flame temperature at pressurized conditions. The uniqueness of the test facility is the method of preheating the air to the compressor discharge temperature of a gas turbine at high-pressure ratios using the combustion exhaust gas and a compact air-to-air heat exchanger. The exhaust dampers and dilution airflows control the preheated-air temperature. The other characteristic of the test facility is the competence of testing NOx reduction combustion systems using steam or inert gas. The facility has the capability to perform steam injection experiments to examine the combustion stability with massive steam injection rates of up to 20% of air mass flow rate. The test process is fully automated with computer data acquisition and digital control. Combustion systems such as GE Frame 5P, 6B, 7EA, and Westinghouse 501D5A have been tested. With Cheng Power’s unique NOx reduction system (CLN™ - Cheng Low NOx System), less than 5 ppm NOx and very low level of CO were obtained for these combustion systems without hardware modification. The facility is also capable of testing Dry-Low-NOx (DLN) combustion systems. The test system is also assisted by a commercial computer program (Star-CD) to estimate the pressurization effect for extrapolating the test results. The pressure dependence can be simulated with the unique combustion geometry, type of fuel, and onset of turbine inlet temperature, respectively. The results depict the detail of the flame structure under various combustion chamber design characteristics. The model pressurization results correlate well with our experimental results as well as results in the literature.Copyright © 2002 by ASME
Current Approaches to the Treatment of Post-Stroke Aphasia

Aphasia, impairment of language after stroke or other neurological insult, is a common and often devastating condition that affects nearly every social activity and interaction. Behavioral speech and language therapy is the mainstay of treatment, although other interventions have been introduced to augment the effects of the behavioral therapy. In this narrative review, we discuss advances in aphasia therapy in the last 5 years and focus primarily on properly powered, randomized, controlled trials of both behavioral therapies and interventions to augment therapy for post-stroke aphasia. These trials include evaluation of behavioral therapies and computer-delivered language therapies. We also discuss outcome prediction trials as well as interventional trials that have employed noninvasive brain stimulation, or medications to augment language therapy. Supported by evidence from Phase III trials and large meta-analyses, it is now generally accepted that aphasia therapy can improve language processing for many patients. Not all patients respond similarly to aphasia therapy with the most severe patients being the least likely responders. Nevertheless, it is imperative that all patients, regardless of severity, receive aphasia management focused on direct therapy of language deficits, counseling, or both. Emerging evidence from Phase II trials suggests transcranial brain stimulation is a promising method to boost aphasia therapy outcomes.
Cost-Effectiveness of Saxagliptin Compared With Glibenclamide as a Second-Line Therapy Added to Metformin for Type 2 Diabetes Mellitus in Ethiopia

Background. Metformin is a widely accepted first-line pharmacotherapy for patients with type 2 diabetes mellitus (T2DM). Treatment of T2DM with glibenclamide, saxagliptin, or one of the other second-line treatment agents is recommended when the first-line treatment (metformin) cannot control the disease. However, there is little evidence on the additional cost and cost-effectiveness of adding second-line drugs. Therefore, this study aimed to estimate the cost-effectiveness of saxagliptin and glibenclamide as second-line therapies added to metformin compared with metformin only in T2DM in Ethiopia. Methods. This cost-effectiveness study was conducted in Ethiopia using a mix of primary data on cost and best available data from the literature on the effectiveness. We measured the interventions’ cost from the providers’ perspective in 2019 US dollars. We developed a Markov model for T2DM disease progression with five health states using TreeAge Pro 2020 software. Disability-adjusted life year (DALY) was the health outcome used in this study, and we calculated the incremental cost-effectiveness ratio (ICER) per DALY averted. Furthermore, one-way and probabilistic sensitivity analysis were performed. Results. The annual unit cost per patient was US$70 for metformin, US$75 for metformin + glibenclamide, and US$309 for metformin + saxagliptin. The ICER for saxagliptin + metformin was US$2259 per DALY averted. The ICER results were sensitive to various changes in cost, effectiveness, and transition probabilities. The ICER was driven primarily by the higher cost of saxagliptin relative to glibenclamide. Conclusion. Our study revealed that saxagliptin is not a cost-effective second-line therapy in patients with T2DM inadequately controlled by metformin monotherapy based on a gross domestic product per capita per DALY averted willingness-to-pay threshold in Ethiopia (US$953).
Early palliative care associated with lower costs for adults with advanced cancer: evidence from Hungary.

OBJECTIVE Palliative Care Consult Service (PCCS) programme was established in Hungary to provide palliative care to hospitalised patients with complex needs and to coordinate integrated care across providers. The aim of this study was to measure the association of PCCS with healthcare costs from payer's perspective. METHODS Study population consisted of patients with metastatic cancer, who were admitted to the Clinical Centre of the University of Pécs between 2014 and 2016. Patients who did not die within 180 days from enrolment were excluded. Patients receiving services from PCCS team (intervention patients) were compared to patients receiving usual care (controls). The two populations were matched using propensity scores. Data were obtained from electronic medical records linked to claims data. RESULTS For patients who were involved in PCCS at least 60 days before their death, the costs of care outside the acute hospital were higher. However, this was offset by savings in hospital costs so that the total healthcare cost was significantly reduced (p = 0.034). The proportion of patients who died in the hospital was lower in the PCCS group compared to the usual care group (66% vs. 85%, p = 0.022). CONCLUSION Timely initiation of palliative care for hospitalised patients is associated with cost savings for the healthcare system.
Social synchronization during joint attention in children with autism spectrum disorder

We explored the social synchronization of gaze‐shift behaviors when responding to joint attention in children with autism spectrum disorder (ASD). Forty‐one children aged 5 to 8 with ASD and 43 typically developing (TD) children watched a video to complete the response to joint attention (RJA) tasks, during which their gaze data were collected. The synchronization of gaze‐shift behaviors between children and the female model in the video was measured with the cross‐recurrence quantification analysis (CRQA). Ultimately, we discovered that children with ASD had the ability to synchronize their gaze shifts with the female model in the video during RJA tasks. Compared to the TD children, they displayed lower levels of synchronization and longer latency in this synchronized behavior. These findings provide a new avenue to deepen our understanding of the impairments of social interaction in children with ASD. Notably, the analytic method can be further applied to explore the social synchronization of numerous other social interactive behaviors in ASD.
Sexual healthcare professionals’ views on the rapid provision of remote services at the beginning of COVID-19 pandemic: A mixed-methods study

Introduction: The COVID-19 pandemic and social distancing measures forced sexual health services to engage with patients remotely. We aimed to understand perceived barriers and facilitators to the provision of digital sexual health services during the first months of the pandemic. Methods: An online survey and qualitative interviews with UK sexual healthcare professionals recruited online and via snowball sampling were conducted in May–July 2020. Results: Amongst 177 respondents (72% female, 86% White, mean age = 46, SD = 9), most utilised telephone and email as their main communication channels; however, their perceived effectiveness varied (94% and 66%, respectively). Most agreed that staff needed additional training (89%), the available technology was not adequate (66%) and health professionals were hesitant to provide online consultations (46%). They had positive attitudes towards digitalisation, improving service quality and cost-effectiveness but were concerned about exacerbating health inequalities. Discussion: The study identifies a need for clear guidelines and training around the use of digital tools as well as a demand for investment in hardware and software required for the provision of remote services. Future research needs to explore the acceptability, safety and effectiveness of various digital tools to narrow health inequalities in sexual health service users.
Substrate Utilization Patterns During BTEX Biodegradation by an o-Xylene-Degrading Bacterium Ralstonia sp. PHS1

The biodegradation of BTEX components (benzene, toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene) individually and in mixtures was investigated using the o-xylene-degrading thermo-tolerant bacterium Ralstonia sp. strain PHS1, which utilizes benzene, toluene, ethylbenzene, or o-xylene as its sole carbon source. The results showed that as a single substrate for growth, benzene was superior to both toluene and ethylbenzene. While growth inhibition was severe at higher o-xylene concentrations, no inhibition was observed (up to 100 mg l -1 ) with ethylbenzene. In mixtures of BTEX compounds, the PHS1 culture was shown to degrade all six BTEX components and the degradation rates were in the order of benzene, toluene, o-xylene, ethylbenzene, and m- and p-xylene. m-Xylene and p-xylene were found to be co-metabolized by this microorganism in the presence of the growth-supporting BTEX compounds. In binary mixtures containing the growth substrates (benzene, toluene, ethylbenzene, and o-xylene), PHS 1 degraded each BTEX compound faster when it was alone than when it was a component of a BTEX mixture, although the degree of inhibition varied according to the substrates in the mixtures. p-Xylene was shown to be the most potent inhibitor of BTEX biodegradation in binary mixtures. On the other hand, the degradation rates of the non-growth substrates (m-xylene and p-xylene) were significantly enhanced by the addition of growth substrates. The substrate utilization patterns between PHS1 and other microorganisms were also examined.
Treatment of lymphocyte‐variant hypereosinophilic syndrome (L‐HES): what to consider after confirming the elusive diagnosis

Lymphocyte‐variant hypereosinophilic syndrome (L‐HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin‐5 (IL‐5). Treatment is challenging because L‐HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L‐HES. In all, 25 studies were selected; two were randomised controlled trials of IL‐5 blockade, which included some patients with L‐HES, and the rest were observational studies. Corticosteroids are often used as first‐line therapy, but patients with L‐HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferon‐alpha (IFN‐α), anti‐IL‐5 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T‐cell activation and proliferation, or IL‐5 directly. Although effective, IFN‐α and cyclosporine were commonly reported to cause side‐effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti‐IL‐5 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L‐HES.