Miracle-dz/UniFAR-FTUs huggingface dataset:
Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG‐Syt1‐SV2 plasma membrane nanocluster for synaptic vesicle entry

The unique nerve terminal targeting of botulinum neurotoxin type A (BoNT/A) is due to its capacity to bind two receptors on the neuronal plasma membrane: polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Whether and how PSGs and SV2 may coordinate other proteins for BoNT/A recruitment and internalization remains unknown. Here, we demonstrate that the targeted endocytosis of BoNT/A into synaptic vesicles (SVs) requires a tripartite surface nanocluster. Live‐cell super‐resolution imaging and electron microscopy of catalytically inactivated BoNT/A wildtype and receptor‐binding‐deficient mutants in cultured hippocampal neurons demonstrated that BoNT/A must bind coincidentally to a PSG and SV2 to target synaptic vesicles. We reveal that BoNT/A simultaneously interacts with a preassembled PSG‐synaptotagmin‐1 (Syt1) complex and SV2 on the neuronal plasma membrane, facilitating Syt1‐SV2 nanoclustering that controls endocytic sorting of the toxin into synaptic vesicles. Syt1 CRISPRi knockdown suppressed BoNT/A‐ and BoNT/E‐induced neurointoxication as quantified by SNAP‐25 cleavage, suggesting that this tripartite nanocluster may be a unifying entry point for selected botulinum neurotoxins that hijack this for synaptic vesicle targeting.
Septuagenarians with acute type A aortic dissection undergoing extended aortic arch repair: a retrospective cohort study

Background: Extended arch repair in elderly patients with acute type A aortic dissection (ATAAD) remains challenging for cardiac surgeons. Data on extended arch repair for ATAAD in septuagenarians are scarce. Materials and methods: Consecutive adult patients with ATAAD undergoing extended arch repair from January 2015 to December 2021 were identified. According to age at presentation, 714 eligible patients were entered into either an elderly group (septuagenarians, n=65) or a control group (patients aged less than 70, n=649). Using propensity score matching, 60 pairs of patients were successfully established at a 1:1 ratio. In-hospital outcomes (operative death and major postoperative morbidity) and midterm outcomes (survival and aortic reintervention) were compared before and after matching. Results: Operative death occurred in 64 patients (9.0%), including seven septuagenarians (10.8%) and 57 (8.8%) from the control group, without significant differences between groups before and after matching (P=0.593 and 0.774, respectively). Major postoperative morbidity was observed in 298 patients (41.7%), including 29 (44.6%) in the elderly group and 269 (41.4%) in the control group (P=0.622). Age-based grouping was not significantly associated with operative mortality or major postoperative morbidity in the crude, multivariable, and propensity score analyses. The 5-year cumulative survival and cumulative aortic reintervention rates in the elderly group were 83.5 and 4.6%, respectively, which were not statistically different from those in the control group before and after matching. Conclusions: Extended arch repair may be safely and effectively performed in septuagenarians with ATAAD, with in-hospital and midterm outcomes comparable to those obtained in patients aged less than 70 years.
The role of bioimpedance analysis in overweight and obese patients with acute heart failure: a pilot study

Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients.
Equitable access to speech practice for rural Australian children using the SayBananas! mobile game

Abstract Purpose To evaluate the effect, usage, and user-experience for SayBananas! , a Mario-style mobile game providing Australian children access to high-dose individualised speech therapy practice. Method Participants were 45 rural Australian children with speech sound disorders (SSD; 4;4–10;5 years) with internet access. This mixed-methods study involved: (a) recruitment, (b) eligibility screening, (c) questionnaire, (d) online pre-assessment, (e) SayBananas! intervention using motor learning principles (4 weeks, 10–15 target words), and (f) online post-assessment and interview. Usage and performance were automatically monitored. Result Most participants were highly engaged with SayBananas! completing a median of 44.71 trials/session (∼45% of the 100 trial/session target, range 7–194). After intervention, participants made significant gains on treated words and on formal assessment of percentage of consonants, vowels, and phonemes correct. There was no reliable change for parent-rated intelligibility or children’s feelings about talking. The number of practice sessions was significantly correlated with percent change on treated words. On average, children rated the app as “happy/good/fun” providing detailed drawings of playing SayBananas! Families provided high ratings of engagement, functionality, aesthetics, and quality. Conclusion SayBananas! is a viable and engaging solution for rural Australian children with SSD to gain access to equitable, cost-effective speech practice. The amount of app use was associated with amount of speech production improvement over a 4-week period.
Exploring Primary Healthcare Experiences and Interest in Mobile Technology Engagement Amongst an Urban Population Experiencing Barriers to Care

Mobile phone–based engagement approaches provide potential platforms for improving access to primary healthcare (PHC) services for underserved populations. We held two focus groups (February 2020) with residents (n = 25) from a low-income urban neighbourhood (downtown Vancouver, Canada), to assess recent healthcare experiences and elicit interest in mobile phone–based healthcare engagement for underserved residents. Note-based analysis, guided by interpretative description, was used to explore emerging themes. Engagement in PHC was complicated by multiple, intersecting personal-level and socio-structural factors, and experiences of stigma and discrimination from care providers. Perceived inadequacy of PHC services and pervasive discrimination reported by participants indicate a significant and ongoing need to improve client–provider relationships to address unmet health needs. Mobile phone–based engagement was endorsed, highlighting phone ownership and client–provider text-messaging, facilitated by non-clinical staff such as peers, as helpful to strengthening retention and facilitating care team connection. Concerns raised included reliability, cost, and technology and language accessibility.
Minnaert constant of several forest types from SPOT/HRV data.

Minnaert correction method is one of the most appropriate models that correct topographic effects on remotely sensed data. However, the variations of the Minnaert constants have not been examined for any forest types. The purpose of this research was to investigate the extent of the variation of the Minnaert constant in three different forest types. Three forest types were selected for the analysis ; broad-leaved natural forest, coniferous plantations, and bamboo forest. 7 scenes of SPOT/HRV data observed in 1997 were selected and orthorectified with digital elevation models and digital topographic maps. The Minnaert constants were obtained through a regression analysis between solar incidence angles and the original satellite data. The results showed bands 1 and 2 indicated the seasonal variation of Minnaert constant, which had the peak in summer. In those bands, there were negative correlations between the solar zenith angles and the Minnaert constants. On the other hand, the band 3 indicated unclear variations in the Minnaert constants rather slight fluctuations. Then there was not significant correlation between the solar zenith angles and the Minnaert constants of the band 3. The results of this study suggested that visible band and near infrared one differ in the annual change pattern of the Minnaert constant.
Preparation and exchange transfusion effect of a double polymerization human umbilical cord haemoglobin of red blood cell substitute

Abstract The development of haemoglobin-based oxygen carrier (HBOC) is an excellent supplement to pre-hospital emergency blood transfusions. In this study, a new type of HBOC was prepared by using human cord haemoglobin (HCHb) and glutaraldehyde (GDA) and Bis(3,5-dibromosalicyl) fumarate (DBBF) to modify (DBBF-GDA-HCHb), the changes of physicochemical indexes during its preparation were evaluated, while a traditional type of GDA-HCHb was prepared, and the oxygen-carrying capacity of two type of HBOC was evaluated by a rat model of 135.0% exchange transfusion (ET). Eighteen SD male rats were selected, and were randomly divided into control group (5.0% albumin), DBBF-GDA-HCHb group and GDA-HCHb group. The 12 h survival rate of the C group was 16.67%, and the two HBOC groups were both 83.33%. Compared with GDA-HCHb, DBBF-GDA-HCHb can reduce lactic acid content by supplying oxygen to hypoxic tissues in a more timely manner, and can also can improve the reduction of MAP due to ischaemia.
Understanding of and clinical approach to cardiometabolic transition at the menopause

Abstract Cardiovascular disease (CVD) represents the leading cause of death and accounts for almost 50% of all deaths in women worldwide. The menopausal transition is associated with central body fat accumulation, a decrease in energy expenditure, weight gain, insulin resistance and a pro-atherogenic lipid profile. Moreover, menopause is independently associated with an adverse effect on functional and structural indices of subclinical atherosclerosis. Women with premature ovarian insufficiency have heightened CVD risk compared to women of natural age at menopause. Furthermore, women with severe menopausal symptoms may have a more adverse cardiometabolic profile than those without symptoms. We reviewed the latest evidence on the cardiovascular management of perimenopausal or postmenopausal women. Clinicians should aim for cardiovascular risk stratification, followed by dietary and lifestyle advice as required based on individual needs. The medical management of cardiometabolic risk factors at midlife should always be individualized, focusing on hypertension, diabetes and dyslipidemia. Menopausal hormone therapy, when prescribed for the management of bothersome menopausal symptoms or for the prevention of osteoporosis, has also a beneficial effect on cardiometabolic risk factors. This narrative review aims to summarize the cardiometabolic alternations occurring during the menopausal transition and to outline the appropriate prevention strategies to prevent future cardiovascular adverse outcomes.
Character sums with exponential functions

Let be an integer of multiplicative order t ≥ 1 modulo a prime p. Sums of the form S * (p,t,a)= exp (2πia zs /p) are introduced and estimated, with F=(z 1 ,.,z T ) a sequence such that kz 1 ,. , kz T is a permutation of z 1 ,. , Z T , both sequences taken modulo t, for sufficiently many distinct modulo t values of k. Such sequences include x n for x = 1,. , t with an integer n ≥ 1; x n for x = 1,. , t and gcd (x, t) = 1 with an integer n ≥ 1; e x for x = 1,. , T with an integer e, where T is the period of the sequence e x modulo t. Some of the results can be extended to composite moduli and to sums of multiplicative characters as well. Character sums with the above sequences have some cryptographic motivation and applications and have been considered in several papers by J. B. Friedlander, D. Lieman and I. E. Shparlinski. In particular several previous bounds are generalized and improved.
Longitudinal modifiable risk and protective factors of internet gaming disorder: A systematic review and meta-analysis

Abstract Background and aims The study aims to thoroughly understand the causal and precedent modifiable risk or protective factors for Internet Gaming Disorder (IGD), a newly defined and prevalent mental disorder. Methods We performed a systematic review on quality-designed longitudinal studies based on five online databases: MEDLINE, PsycINFO, Embase, PubMed, and Web of Science. Studies were included in the meta-analysis if they addressed IGD, adopted longitudinal, prospective, or cohort study designs, presented modifiable factors of IGD, and reported the effect sizes for correlations. Pooled Pearson's correlations were calculated using the random effects model. Results Thirty-nine studies with 37,042 subjects were included. We identified 34 modifiable factors, including 23 intrapersonal factors (e.g., gaming time, loneliness, etc.), 10 interpersonal factors (e.g., peer relationship, social support, etc.), and 1 environmental factor (i.e., school engagement). Age, the male ratio, study region, and study years were significant moderators. Discussion and conclusions Intrapersonal factors were stronger predictors than interpersonal and environmental factors. It may imply that individual-based theories are more powerful to explain the development of IGD. Longitudinal research on the environmental factors of IGD was lacking; more studies are warranted. The identified modifiable factors would help to guide effective interventions for IGD reduction and prevention.
Euro-Burn I: Assessment of burnout syndrome in health workers in a mediterranean country during the SARS-CoV-2 pandemic

Background: Burnout syndrome (BS) has a negative impact among health professionals. Aims: Our research objective is to quantify the level of burnout in health workers of the Spanish National Health System during the COVID-19 pandemic using and comparing two independent measurement instruments. Methods: Cross-sectional, descriptive and multicenter study conducted through an anonymous online survey among health workers of the National Health System, measuring the level of burnout using the Maslach Burnout Inventory (MBI) and the Copenhagen Burnout Inventory (CBI). Results: A total of 448 questionnaires were analyzed, the mean age of the participants was 43.53 years (range: 20–64), 365 (81.5%) women. 161 (35.9%) participants presented BS measured with the MBI and 304 (67.9%) measured with the CBI. Regarding work contract, those who had greater job stability presented a higher degree of cynicism with respect to the eventual ones (p = .010), the eventual ones presenting higher mean scores in professional efficacy (p = .034). Urban workers had higher scores of exhaustion (p < .001) and cynicism (p < .001) than those living in rural areas. When comparing both tests, a high predictive value for exhaustion and cynicism was found to measure BS through the CBI (AUC = 0.92 and 0.84, respectively) and a low AUC with respect to the predictive value for efficacy (AUC = 0, 59). Conclusions: The results obtained show a high level of BS among the health workers who participated in our study. Both tests have an excellent correlation in the degree of exhaustion and cynicism, but not in efficacy. The BS measurement must be performed with at least two validated instruments to increase its reliability.
Long read genome assemblers struggle with small plasmids

Whole-genome sequencing has become a preferred method for studying bacterial plasmids, as it is generally assumed to capture the entire genome. However, long-read genome assemblers have been shown to sometimes miss plasmid sequences – an issue that has been associated with plasmid size. The purpose of this study was to investigate the relationship between plasmid size and plasmid recovery by the long-read-only assemblers, Flye, Raven, Miniasm, and Canu. This was accomplished by determining the number of times each assembler successfully recovered 33 plasmids, ranging from 1919 to 194 062 bp in size and belonging to 14 bacterial isolates from six bacterial genera, using Oxford Nanopore long reads. These results were additionally compared to plasmid recovery rates by the short-read-first assembler, Unicycler, using both Oxford Nanopore long reads and Illumina short reads. Results from this study indicate that Canu, Flye, Miniasm, and Raven are prone to missing plasmid sequences, whereas Unicycler was successful at recovering 100 % of plasmid sequences. Excluding Canu, most plasmid loss by long-read-only assemblers was due to failure to recover plasmids smaller than 10 kb. As such, it is recommended that Unicycler be used to increase the likelihood of plasmid recovery during bacterial genome assembly.
Psychiatric nurses’ experience of moral distress: Its relationship with empowerment and coping

Background Research has shown that moral distress negatively impacts nurses, patients, and organizations; however, several scholars have argued that it can be an opportunity for positive outcomes. Thus, factors that may mitigate moral distress and catalyze positive change need to be explored. Research aim The purpose of this study was to explore the relationships among structural and psychological empowerment, psychiatric staff nurses’ experience of moral distress, and strategies for coping with moral distress. Research design A descriptive cross-sectional correlational study. Participants and research context A total of 180 registered nurses working in psychiatric hospitals in Japan participated. This study examined relationships among key variables using four questionnaires to assess structural and psychological empowerment, moral distress for psychiatric nurses, and coping strategies. Statistical analyses of correlations and multiple regressions were conducted. Ethical considerations The study was approved by the institutional review board at the author’s affiliated university. Findings Psychiatric nurses perceived moderate levels of structural and psychological empowerment, and their experiences of moral distress were related to low staffing. Structural empowerment was negatively related to the frequency of moral distress but not the intensity. Contrary to expectations, psychological empowerment was not found to mitigate nurses’ moral distress. Multivariate regression analyses revealed that the significant predictors of moral distress were the leaving issues unresolved coping style, the problem-solving coping style, and a lack of formal power, which explained 35% and 22% of the variance in the frequency and intensity of moral distress, respectively. Conclusions In psychiatric hospitals in Japan, nurses experience moral distress that compromises the quality of care they provide. Therefore, formal support for nurses in voicing and investigating their moral concerns is required to bestow formal power by establishing a ward culture that includes shared governance.
Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine

Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 μg/ml; n = 40), dexmedetomidine (1.5 ng/ml; n = 40), sevoflurane (0.9% end-tidal; n = 40), S-ketamine (0.75 μg/ml; n = 20), or saline placebo (n = 20) for 60 min using target-controlled infusions or vaporizer with end-tidal monitoring. Disconnectedness was defined as unresponsiveness to verbal commands probed at 2.5-min intervals and unawareness of external events in a postanesthesia interview. High-resolution positron emission tomography (PET) was used to quantify regional cerebral metabolic rates of glucose (CMRglu) utilization. Contrasting scans where the subjects were classified as connected and responsive versus disconnected and unresponsive revealed that for all anesthetics, except S-ketamine, the level of thalamic activity differed between these states. A conjunction analysis across the propofol, dexmedetomidine and sevoflurane groups confirmed the thalamus as the primary structure where reduced metabolic activity was related to disconnectedness. Widespread cortical metabolic suppression was observed when these subjects, classified as either connected or disconnected, were compared with the placebo group, suggesting that these findings may represent necessary but alone insufficient mechanisms for the change in the state of consciousness. SIGNIFICANCE STATEMENT Experimental anesthesia is commonly used in the search for measures of brain function which could distinguish between global states of consciousness. However, most previous studies have not been designed to separate effects related to consciousness from other effects related to drug exposure. We employed a novel study design to disentangle these effects by exposing subjects to predefined EC50 doses of four commonly used anesthetics or saline placebo. We demonstrate that state-related effects are remarkably limited compared with the widespread cortical effects related to drug exposure. In particular, decreased thalamic activity was associated with disconnectedness with all used anesthetics except for S-ketamine.
Mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signaling is involved in phagocytosis activation during THP-1 cell differentiation

Mechanistic/mammalian target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase that plays a major role in cell metabolism. Although mTORC1 inhibitors are known to exert immunosuppressive effects, their effects on immune cells are not fully understood. In the present study, we examined the involvement of mTORC1 in the differentiation and functions of macrophages using THP-1 cells, which are derived from human monocytic leukemia and differentiate into macrophage-like cells upon treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We also examined the effects of two mTOR inhibitors, Torin 1 and rapamycin, on TPA-stimulated THP-1 cells. Although mTORC1 activation was observed upon TPA stimulation, mTOR inhibitors did not affect TPA-induced morphological changes or expression of the general macrophage marker, CD11b. In contrast, phagocytosis and fluid endocytosis were significantly impaired by the mTOR inhibitors. Endocytosis suppression was observed when mTOR inhibitors were added during differentiation, but not before or after differentiation, suggesting that endocytosis suppression altered the direction of differentiation. Furthermore, mTOR inhibitors altered the expression of M1/M2 polarization markers. These results suggest that the immunosuppressive effects of mTOR inhibitors may involve the suppression of macrophage endocytosis caused by abnormal cell differentiation.