Miracle-dz/UniFAR-FTUs huggingface dataset:
A Depletion of Stop Codons in lincRNA is Owing to Transfer of Selective Constraint from Coding Sequences

Abstract Although the constraints on a gene’s sequence are often assumed to reflect the functioning of that gene, here we propose transfer selection, a constraint operating on one class of genes transferred to another, mediated by shared binding factors. We show that such transfer can explain an otherwise paradoxical depletion of stop codons in long intergenic noncoding RNAs (lincRNAs). Serine/arginine-rich proteins direct the splicing machinery by binding exonic splice enhancers (ESEs) in immature mRNA. As coding exons cannot contain stop codons in one reading frame, stop codons should be rare within ESEs. We confirm that the stop codon density (SCD) in ESE motifs is low, even accounting for nucleotide biases. Given that serine/arginine-rich proteins binding ESEs also facilitate lincRNA splicing, a low SCD could transfer to lincRNAs. As predicted, multiexon lincRNA exons are depleted in stop codons, a result not explained by open reading frame (ORF) contamination. Consistent with transfer selection, stop codon depletion in lincRNAs is most acute in exonic regions with the highest ESE density, disappears when ESEs are masked, is consistent with stop codon usage skews in ESEs, and is diminished in both single-exon lincRNAs and introns. Owing to low SCD, the maximum lengths of pseudo-ORFs frequently exceed null expectations. This has implications for ORF annotation and the evolution of de novo protein-coding genes from lincRNAs. We conclude that not all constraints operating on genes need be explained by the functioning of the gene but may instead be transferred owing to shared binding factors.
The relationship between mental disorders and actual and desired subjective social status

Abstract Aims Mental disorders are associated with lower subjective social status (SSS), but a more nuanced understanding of this relationship is needed. We examined the influence of disorder age of onset and recency on SSS and studied whether mental disorders are also associated with the discrepancy between actual and desired SSS. Method Data are from the baseline and second wave of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Mental disorders were assessed with the Composite International Diagnostic Interview (CIDI 3.0), while both actual and desired SSS were assessed with a ten-rung ladder. Linear regression was used to examine the association between mental disorders and SSS. Results Of 5303 participants, 2237 had a lifetime mental disorder at baseline. These participants reported significantly lower actual SSS (6.28) at follow-up than healthy participants (6.66, B = −0.38 [95% CI −0.48 to −0.27], p < 0.001) and a significantly greater actual-desired SSS discrepancy (1.14 v. 1.05 after controlling for actual SSS, B = 0.09 [0.01–0.17], p = 0.024). Lower age of onset of the first mental disorder was marginally significantly associated with lower actual SSS (B = 0.006 [0.000–0.012], p = 0.046). More recent disorders were also associated with lower actual SSS (B = 0.015 [0.005–0.026], p = 0.005), such that participants whose disorder remitted ⩾6 years before baseline were statistically indistinguishable from healthy participants. Conclusions Lifetime mental disorders are associated with lower actual SSS and a slightly greater discrepancy between actual and desired SSS. However, people with mental disorders in (long-term) remission have a similar social status as healthy participants.
Dual blockade of IL‐4 and IL‐13 with dupilumab, an IL‐4Rα antibody, is required to broadly inhibit type 2 inflammation

Dupilumab, a fully human monoclonal antibody that binds IL‐4Rα and inhibits signaling of both IL‐4 and IL‐13, has shown efficacy across multiple diseases with underlying type 2 signatures and is approved for treatment of asthma, atopic dermatitis, and chronic sinusitis with nasal polyposis. We sought to provide a comprehensive analysis of the redundant and distinct roles of IL‐4 and IL‐13 in type 2 inflammation and report dupilumab mechanisms of action.
The case for trauma‐informed aged care

Up to 70% of older people have experienced at least one potentially traumatic event in their lives. Distress and psychological damage (including challenges in functioning or coping) can occur where the event threatens the person's safety or overwhelms their ability to integrate their emotional experience (eg, understand and make sense of the event). However, the extent of distress will vary. Between 20 and 40% of survivors will develop clinically significant posttraumatic stress disorder (PTSD), a syndrome characterised by intrusive reliving of the trauma, avoidance of thoughts and feelings associated with the trauma, mood disturbance, hyperarousal, and dissociation. The impact of exposure to psychological trauma can be pervasive and continue for many years. Core difficulties tend to persist or are at least present intermittently over the life course. Reemergence in older age is common. “Complex” or developmental trauma, caused by prolonged relational neglect or abuse, is increasingly recognised to fundamentally impede core regulation and interpersonal skills. Trauma-informed care is a framework that prioritises assessment of trauma and its current effects, amends procedures to account for triggers, and creates an environment that maximises control for the survivor. It is applied across mental health systems and is wellestablished to promote staff and care recipient safety and satisfaction, reduce the risk of re-traumatisation, and minimise adverse events. However, trauma-informed care is not widely implemented in generalist aged care settings. The aim of this discussion is to make a case for widespread implementation of trauma-informed models of care in generalist aged care settings. Similar cases have previously been made for hospice and palliative care and generalist health services based on the potential mutual benefits for both service users and providers. We will also discuss the research, policy, and clinical advancements that would be required to achieve widespread systems change.
LncRNA LOXL1-AS1 inhibited cell proliferation, migration and invasion as well as induced apoptosis in breast cancer via regulating miR-143-3p.

OBJECTIVE In recent years, studies have shown that lncRNA plays an essential regulatory role in biological life activities. In disease and cancer research, the function of lncRNA is closely related to inflammatory response, tumor formation and cellular metabolism. Breast cancer is one of the most common malignant tumors in women. The research on the pathogenesis of breast cancer is the focus of current research. Although the regulatory mechanisms of some lncRNAs have been proven, the complexity of cancer regulation has led to incomplete research. MATERIALS AND METHODS The expression of LOXL1-AS1 and miR-143-3p was measured using qRT-PCR. Western blot was used to detect CDK, Cyclin D1, MMP-2, MMP-9, Bcl-2, Bax and Cleaved caspase-3 protein expression. MTT assay and transwell assay were applied to analyze cell proliferation, migration and invasion, respectively. Cell apoptosis rate of transfected cells was measured with flow cytometry. Luciferase reporter assay was applied to verify the relationship between LOXL1-AS1 and miR-143-3p. RESULTS In this study, we found that LOXL1-AS1 expression was induced while miR-142-3p expression was decreased in breast cancer tissues and cells, implying that LOXL1-AS1 and miR-143-3p play an important role in cell progression of breast cancer. Further investigation showed that silencing LOXL1-AS1 inhibited proliferation, promoted cell apoptosis and decreased the capacity of cell migrated and invasive in breast cancer cells. The analysis of luciferase reporter assay determined that LOXL1-AS1 directly targeted miR-143-3p in breast cancer cells. The rescue experiments further proved that miR-143-3p reversed the inhibited effects of si- LOXL1-AS1 on breast cancer cells. CONCLUSIONS In this study, we verified that LncRNA LOXL1-AS1 inhibited cell proliferation, migration and invasion as well as induced apoptosis in breast cancer via regulating miR-143-3p, providing a novel therapeutic target and improving understanding of the regulatory mechanism of cell progression in breast cancer.
Perfusion dynamics of the medial sural artery perforator (MSAP) flap in lower extremity reconstruction using laser Doppler perfusion imaging (LDPI): a clinical study

Abstract Perforator flaps are a mainstay in reconstructive surgical practice but are limited by complications, including flap failure, resulting from flap hypoperfusion. This study aimed to characterize the early post-operative perfusion dynamics of the medial sural artery perforator (MSAP) flap in lower extremity reconstruction using laser Doppler perfusion imaging (LDPI). 12 patients, recruited between 2014 and 2015, with lower extremity reconstructions using free MSAP flaps were assessed for perfusion using a hand-held colour Doppler ultrasound device on days 1, 3, and 5 post-operatively. Perfusion at four distinct zones was assessed; whole flap, control zone, perforator zone, and distal zone, by a single operator using a standardized technique. The perforator zone was noted to have the highest relative perfusion of all zones measured across all post-operative days, and this was correlated with whole flap perfusion (r = 0.82, p = 0.002). No significant perfusion differences were found within any of the zones over the 5-day period. The perfusion at the distal zone was not found to correlate with either the perforator zone perfusion, flap length, flap length to width ratio or smoking status (p > 0.05). Perfusion of the MSAP flap can adequately be monitored using LDPI at any point throughout the flap, though is highest at the perforator zone, and remains constant in the early post-operative period.
Antibody Fragment F(ab')2 Targeting Caveolae-Associated Protein PV1 for Selective Kidney Targeting and Retention.

Targeted strategies to deliver and retain drugs to kidneys are needed to improve drug accumulation and efficacy in a myriad of kidney diseases. These drug delivery systems show potential for improving the therapeutic windows of drugs acting in the kidney. Biodistribution of antibody-based therapeutics in vivo is governed by several factors including binding affinity, size and valency. Investigations of how the biophysical and biochemical properties of biologics enable them to overcome biological barriers and reach kidneys are therefore of interest. Although renal accumulation of antibody fragments in cancer diagnostics and treatment has been observed, reports on effective delivery of antibody fragments to the kidneys remain scarce. Previously we demonstrate that targeting plasmalemma vesicle-associated protein (PV1), a caveolae-associated protein, can promote accumulation of antibody in both the lungs and the kidneys. Here, by fine-tuning the binding affinity of an antibody toward PV1, we observe that the anti-PV1 antibody with reduced binding affinity lost the capability for kidney targeting while retaining the lung targeting activity, suggesting binding affinity is a critical factor for kidney targeting of the anti-PV1 antibody. We next use the antibody fragment F(ab')2 targeting PV1 to assess the dual effects of rapid kidney filtration and PV1 targeting on kidney selective targeting. Ex vivo fluorescence imaging results demonstrated that, after rapidly accumulating in kidneys at 4 hours, PV1-targeted F(ab')2 was continually retained in kidney at 24 hours, whereas the isotype control F(ab')2 underwent urinary elimination with significantly reduced signaling in kidney. Confocal imaging studies confirmed the localization of PV1 targeted F(ab')2 in kidney. In addition, monovalent antibody fragment (Fab-C4) lost the capability for kidney homing, indicating that the binding avidity of anti-PV1 F(ab')2 is important for kidney targeting. Our findings suggest that PV1-targeted F(ab')2 might be useful as a drug carrier for renal targeting and highlight the importance of affinity optimization for tissue targeting antibodies.
Functional losses in ground spider communities due to habitat-structure degradation under tropical land-use change.

Deforestation and land-use change in tropical regions result in habitat loss and extinction of species that are unable to adapt to the conditions in agricultural landscapes. If the associated loss of functional diversity is not compensated by species colonizing the converted habitats, extinctions might be followed by a reduction or loss of ecosystem functions including biological control. To date, little is known on how land-use change in the tropics alters the functional diversity of invertebrate predators and which key environmental factors may mitigate the decline in functional diversity and predation in litter and soil communities. We applied litter sieving and heat extraction to study ground spider communities and assessed structural characteristics of vegetation and parameters of litter in rainforest and agricultural land-use systems (jungle rubber, rubber and oil palm monocultures) in a Southeast Asian hotspot of rainforest conversion: Sumatra, Indonesia. We found that (1) spider density, species richness, functional diversity and community predation (energy flux to spiders) were reduced by 57-98% from rainforest to oil palm monoculture; (2) jungle rubber and rubber monoculture sustained relatively high diversity and predation in ground spiders, but small cryptic spider species strongly declined; (3) high species turnover compensated losses of some functional trait combinations, but did not compensate for the overall loss of functional diversity and predation per unit area; (4) spider diversity was related to habitat structure such as amount of litter, understory density and understory height, while spider predation was better explained by plant diversity. Management practices that increase habitat structural complexity and plant diversity such as mulching, reduced weeding, and intercropping monocultures with other plants may contribute to maintaining functional diversity of and predation services provided by ground invertebrate communities in plantations.
Why a grassroots Summer Institutes model failed: Exploring obstacles to evidence‐based teaching awareness in low‐awareness, low‐support contexts

As a global phenomenon, the spread of evidence‐based teaching (EBT) in STEM education has been very uneven. Outside of the United States, parts of Europe, and Oceania, EBT awareness is generally regarded as being extremely low. In the United States, programs like the Summer Institutes (SI) have been used to help disseminate awareness and train faculty, precipitating efforts to understand EBT implementation barriers. Such studies have implied a distinction between awareness (the process in which instructors become cognizant of EBT) and enactment (the application of EBT practices in teaching) while generally focusing on the latter in contexts already endowed with high awareness or high support. As a result, very little is known about obstacles to EBT awareness in low‐awareness, low‐support contexts (LALSCs). The present study explores these through interviews and surveys of higher education STEM instructors in South Korea. Our interest was prompted by the failed attempt to implement a nationally accessible, grassroots EBT awareness program modeled off the SI. Several reasons for disinterest in EBT are revealed while faculty with and without research obligations were found to hold significantly different views about the utility of new teaching methods. Potential solutions for improving awareness are explored, revealing institutional supports and mandates through authority as the two options most likely to be effective. It is hoped this work may be used to inform the design of more effective EBT awareness programs, especially those in LALSCs.
The effectiveness of Nurture and Play: a mentalisation-based parenting group intervention for prenatally depressed mothers

Abstract Aim: This randomised control trial (RCT) study examined the effectiveness of a mentalisation-based perinatal group intervention, Nurture and Play (NaP), in improving mother–infant interaction quality and maternal reflective functioning and in decreasing depressive symptoms. Background: Few preventive prenatal interventions have been developed for primary health care settings for mothers with depressive symptoms. Furthermore, previous prenatal intervention studies have only concentrated on reducing depressive symptoms and have not directly addressed enhancing optimal parenting qualities. Methods: The participants were 45 pregnant women with depressive symptoms. Women in the randomly assigned intervention group (n = 24) participated in the manualised, short-term NaP intervention group from pregnancy until the baby’s age of seven months, whereas control group women received treatment as usual (TAU). Maternal emotional availability (EA), reflective functioning (RF) and depressive symptoms were measured before the intervention and at the infants’ 12 months of age, and changes were evaluated using repeated measure analyses of variances (ANOVAs). Findings: The results showed that the intervention group displayed higher maternal sensitivity and RF and more reduction in depressive symptoms than the control group when babies were 12 months old. These findings provide preliminary support for the effectiveness of the NaP intervention.
Exploring the role of elongation Factor-Like 1 (EFL1) in Shwachman-Diamond syndrome through molecular dynamics

Abstract Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder whose patients present mutations in two ribosome assembly proteins, the Shwachman-Bodian-Diamond Syndrome protein (SBDS) and the Elongation Factor-Like 1 (EFL1). Due to the lack of knowledge of the molecular mechanisms responsible for SDS pathogenesis, current therapy is nonspecific and focuses only at alleviating the symptoms. Building on the recent observation that EFL1 single-point mutations clinically manifest as SDS-like phenotype, we carried out comparative Molecular Dynamics (MD) simulations on three mutants, T127A, M882K and R1095Q and wild type EFL1. As supported by small angle X-ray scattering experiments, the obtained data improve the static EFL1 model resulting from the Cryo-electron microscopy and clearly show that all the mutants experience a peculiar rotation, around the hinge region, of domain IV with respect to domains I and II leading to a different conformation respect to that of wild type protein. This study supports the notion that EFL1 function is governed by an allosteric mechanism involving the concerted action of GTPase domain (domain I) and the domain IV and can help point towards new approaches to SDS treatment. Communicated by Ramaswamy H. Sarma
In vitro effects of myo-inositol on normokinetic human semen samples with nonlinear motility.

OBJECTIVE As myo-inositol (MI) deficiency has been associated with impaired sperm quality, we aimed to assess its effects on sperm kinetics objectively, using a computer-aided sperm analysis (CASA) system. PATIENTS AND METHODS We evaluated 59 normokinetic semen samples with nonlinear progressive motility before and after incubation with a solution of MI. The samples were collected from healthy subjects aged 20-40 years who were attending our Laboratory of Seminology for fertility screening. RESULTS We found a significant increase in linear progressive motility (28.2% ± 10.8 vs. 30.9% ± 11.0, T0 vs. T1 respectively; p <0.001) and a significant reduction in nonlinear progressive motility (21.0% ± 9.9 vs. 18.1% ± 10.2, T0 vs. T1 respectively; p <0.001) after incubation with MI. CASA analysis revealed a significant increase in curvilinear velocity (VCL) (65.0 ± 19.0 vs. 67.9 ± 20.4 µm/s, T0 vs. T1 respectively; p = 0.049). Overall, there was an increase in VCL in 42/59 samples (about 70%), mainly from non-smokers. CONCLUSIONS These results suggest that MI has a positive in vitro effect on semen samples, but confirmation is needed through further studies taking into account factors capable of modulating MI response, such as smoking and obesity.
Investigation of Antituberculosis from Medicinal Plant of Community Ethnis in South Sulawesi.

AIMS The aim of this research was to know the species of plant that is used as anti-hematemesis medicine that has the activity of antituberculosis and antituberculosis-MDR and then investigate the phytochemistry characteristics of the compound from every parts of the plant extract that show the activity of antituberculosis and antituberculosis-MDR which is indicated by the value of Minimum Inhibitory Concentration (MIC) of the exctracts. BACKGROUND Tuberculosis is one of the transmitted disease that has been claimed as one of the serious health problem in the world that can cause death as reported in WHO in Global Tuberculosis Report 2014. It has been predicted that 9 million of people suffers tuberculosis disease and 1.5 - 2 million people has dead by this disease. OBJECTIVE Discovery of antituberculosis and antituberculosis MDR agent from medicinal plant of communtity ethnis in south sulawesimethodThe extraction method used in this research was maceration method. The antituberculosis activity test was investigated using MODS and LJ methods. The isolation of the active compound was carried out using Bioassay Guided Fractination and then the compound characteristics were identified using spectroscopy data. RESULT The results showed that extracts from Talas and Kariango plants were active against M. tuberculosis. The FTIR data showed that three isolates obtained from Talas plants contained aliphatic OH and C-O and CH groups. The MIC values of kariango and Talas extracts using the MODS method were 45 mg / ml and 40 mg / ml, respectively. CONCLUSION Talas (Collocasia esculenta) tuber and Kariango rhizome ethanolic extract have a potency for antituberculosis and anti-MDR tuberculosis drug.
Cadaveric Assessment of the Efficacy of Sinus Irrigation After Staged Clearance of the Medial Maxillary Wall

Background Nasal irrigation is a significant component of effective medical management in patients with chronic rhinosinusitis (CRS). Irrigations facilitate distribution of topical medical therapies to affected mucosal surfaces and lavage of hypersecretory mucin and inflammatory products. Objective To compare the effectiveness of cadaveric nasal irrigation distribution and force following different surgical techniques commonly used to open the maxillary sinus. Methods Fresh human cadaver heads were dissected sequentially with uncinectomy, maxillary antrostomy, endoscopic maxillary mega-antrostomy, and modified endoscopic medial maxillectomy. After each surgical technique was performed, the corresponding nasal cavity was irrigated with 240 mL irrigation bottles containing 1/1000 10% fluroscein-labeled free water. A nasal endoscope passed through the canine fossa into a fixed position in the maxillary sinus recorded the extent of sinus irrigation. These videos then underwent blinded assessment by 2 observers assessing for irrigation sinus penetration (scored as 0–4) and force (0–2). Ordinal correlation scores were assessed using Kendall’s tau-B. Results A total of 17 sinuses (age 53.4 ± 12.6, 36.4% female) were assessed. There was a statistically significant positive correlation between increasing extent of maxillary sinus dissection and both sinus penetration and force as assessed by both observers (Kendall’s tau-B P < .0001). Conclusion Increasing the extent of surgical dissection appears to improve penetration and force of the nasal irrigation into the maxillary sinus. This study suggests that while a standard maxillary antrostomy may be sufficient to achieve good topical therapy distribution, more extensive surgery such as a modified medial maxillectomy may be required for sufficient force of sinus lavage.