Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive allometry of sexually selected traits: Do metabolic maintenance costs play an important role?

Sexual selection drives the evolution of some of the most exaggerated traits in nature. Studies on sexual selection often focus on the size of these traits relative to body size, but few focus on energetic maintenance costs of the tissues that compose them, and the ways in which these costs vary with body size. The relationships between energy use and body size have consequences that may allow large individuals to invest disproportionally more in sexually selected structures, or lead to the reduced per‐gram maintenance cost of enlarged structures. Although sexually selected traits can incur energetic maintenance costs, these costs are not universally high; they are dependent on the relative mass and metabolic activity of tissues associated with them. Energetic costs of maintenance may play a pervasive yet little‐explored role in shaping the relative scaling of sexually selected traits across diverse taxa. Also see the video abstract here: https://youtu.be/JyuoQIeA33Q
Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial–mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface liquid layer facilitating microbial colonization and inflammation. The SERPINA1 gene, encoding alpha1-antitrypsin (AAT) protein, is one of the genes implicated in CF, however it remains unknown whether AAT has any influence on CFTR levels. In this study we assessed CFTR protein levels in primary human lung epithelial cells grown at the air-liquid-interface (ALI) alone or pre-incubated with AAT by Western blots and immunohistochemistry. Histological analysis of ALI inserts revealed CFTR- and AAT-positive cells but no AAT-CFTR co-localization. When 0.5 mg/mL of AAT was added to apical or basolateral compartments of pro-inflammatory activated ALI cultures, CFTR levels increased relative to activated ALIs. This finding suggests that AAT is CFTR-modulating protein, albeit its effects may depend on the concentration and the route of administration. Human lung epithelial ALI cultures provide a useful tool for studies in detail how AAT or other pharmaceuticals affect the levels and activity of CFTR.
Development and validation of the maternal blues scale through bonding attachments in predicting postpartum blues.

Background Postpartum blues in Indonesia has a high prevalence at 37% to 67%. Postpartum blues syndrome has been described as varying changes in the affective domain, such as feelings, behavior, or thoughts, that can be influenced by the roles and tasks of women, along with their social, cultural, and economic support. Instruments that measure maternal blues through bonding attachment behavior have never before been developed in Indonesia. Objective This study aimed to develop a maternal blues scale through bonding attachments to predict postpartum blues. Method The research design consisted of three stages: 1) phenomenology design and focus group discussion; 2) development and construction of the maternal blues scale, and 3) a cross-sectional study to measure validation of the scales. Respondents were postpartum mothers in the first week after birth. The sample comprised 501 participants. Sampling was done by consecutive sampling at the Public Health Center (PUSKESMAS) in the South Jakarta area. Data analysis used exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), correlation, and a diagnostic testing . Results Item analysis produced 32 items consisting of 24 items regarding the mother's role and duties as internal factors and eight factors involving social, cultural, and economic support as external factors. Both factors were valid and reliable in predicting postpartum blues with indicators (t loading factors ≥ 1.96, standardized loading factor (SLF) ≥. 50, internal factors: construct reliability (CR) ≥ . 70 and extraction variants (VE) ≥ . 50 and external factors: CR ≥ . 74 to . 83 VE ≥ . 50 to . 63). The relationship with Kennerley's maternity blues as a gold standard was significant. Internal factors had a score of 53, with a sensitivity of 60.2%. The external factors score was 19, with a sensitivity of 77.3%. Conclusion The new scale for postpartum blues prediction developed displayed internal consistency and validity of each indicator (internal and external factors) that was good (CR ≥ .70; VE ≥ .50). This scale provides a feasible tool to predict postpartum blues.
PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Simple Summary Colorectal cancer (CRC) represents a heterogeneous population of tumor cells and cancer stem cells (CSCs) where CSCs are postulated to resist the chemotherapy, and support cancer malignancy. Eliminating CSC can therefore improve CRC therapy and patient survival; however, such strategies have not yielded the desired outcome. Inhibiting autophagy has shown promise in suppressing therapy resistance; however, current autophagy inhibitors have failed in the clinical trials. In the current study, we provided data supporting the efficacy of 36-077, a potent inhibitor of PIK3C3/VPS34, in inhibiting autophagy to kill the CSC to promote the efficacy of colon cancer therapy. Abstract Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.
Deep Learning for Fully Automated Prediction of Overall Survival in Patients with Oropharyngeal Cancer Using FDG-PET Imaging

Purpose: Accurate prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is crucial. We developed an objective and robust deep learning–based fully-automated tool called the DeepPET-OPSCC biomarker for predicting overall survival (OS) in OPSCC using [18F]fluorodeoxyglucose (FDG)-PET imaging. Experimental Design: The DeepPET-OPSCC prediction model was built and tested internally on a discovery cohort (n = 268) by integrating five convolutional neural network models for volumetric segmentation and ten models for OS prognostication. Two external test cohorts were enrolled—the first based on the Cancer Imaging Archive (TCIA) database (n = 353) and the second being a clinical deployment cohort (n = 31)—to assess the DeepPET-OPSCC performance and goodness of fit. Results: After adjustment for potential confounders, DeepPET-OPSCC was found to be an independent predictor of OS in both discovery and TCIA test cohorts [HR = 2.07; 95% confidence interval (CI), 1.31–3.28 and HR = 2.39; 95% CI, 1.38–4.16; both P = 0.002]. The tool also revealed good predictive performance, with a c-index of 0.707 (95% CI, 0.658–0.757) in the discovery cohort, 0.689 (95% CI, 0.621–0.757) in the TCIA test cohort, and 0.787 (95% CI, 0.675–0.899) in the clinical deployment test cohort; the average time taken was 2 minutes for calculation per exam. The integrated nomogram of DeepPET-OPSCC and clinical risk factors significantly outperformed the clinical model [AUC at 5 years: 0.801 (95% CI, 0.727–0.874) vs. 0.749 (95% CI, 0.649–0.842); P = 0.031] in the TCIA test cohort. Conclusions: DeepPET-OPSCC achieved an accurate OS prediction in patients with OPSCC and enabled an objective, unbiased, and rapid assessment for OPSCC prognostication.
The moderating effects of social support and depressive symptoms on pain among elderly multimorbid patients—data from the multicentre, prospective, observational cohort study MultiCare

Abstract Objectives Depressive symptoms and chronic pain are common among patients with multimorbidity creating a complex medical condition for both the patient and the general practitioner. Perceived social support may function as a protective measure. To examine the impact of perceived social support as a potential moderator between depressive symptoms and pain intensity and pain disability in daily activities in multimorbid patients aged 75+. Method Data from 3,189 patients of the German longitudinal cohort study MultiCare were obtained at baseline and follow-ups during 5 years. Multilevel linear mixed-effects analyses were conducted for pain intensity (model 1) and pain disability in daily activities (model 2). The interaction term social support by depression score was included to test for moderation. Results The interaction between social support and depressive symptoms was significantly associated with the pain intensity score 0.41 (SE=.17; 95-CI[.08;.74]) but not with the pain disability score 0.35 (SE=.19; 95-CI[-.01;.72]). Additionally, men and individuals with medium or higher educational level showed reduced pain intensity and disability scores. Pain disability scores increased with age and depressive symptoms. Increased pain scores were also found for body mass index and burden of multimorbidity. Conclusion Perceived social support amplified the association of depressive symptoms on pain intensity and did not show a protective function. The high scores of perceived social support among the participants may point to the practice of secondary gain due to the patients immense health burden.
Validity and Reliability of the German Version of the Locomotor Capabilities Index-5 (LCI-5)

Abstract Background Before foreign language questionnaires, such as patient reported outcome measures (PROMs), can be scientifically used in the national language, guideline-based translation, cultural adaptation and comprehensive verification of their validity and reliability are needed. The aim of this study was to assess the psychometric properties of the German version of the LCI-5 (LCI-5-D) on a sample of people with lower limb amputation (LLA). Methods The LCI-5 was translated into German (LCI-5-D) based on the ISPOR guidelines for cross-cultural adaptation following pilot testing. The final LCI-5-D was administered to n = 52 lower limb amputees in order to determine the validity and reliability of both the total score and the subscores (“basic items” and “advanced items”). Internal consistency (Cronbachʼs alpha), test-retest reliability (ICC2,1), standard error of the mean (SEM), minimal detectable change (MDC), item-to-total correlation, and item-to-subscale correlation were calculated. Floor and ceiling effects were checked. For construct validity, the Rivermead Mobility Index (RMI) and timed up and go (TUG) test were correlated, and differences of defined subgroups (amputation height and prosthesis user type) were calculated. Results On average, the score of the LCI-5-D was 40.13 ± 16.64 points. High ceiling effects were present for the subscale “basic items” (57.7% maximum score). Internal consistency showed excellent results (Cronbachʼs α = 0.97). A strong correlation to the RMI (r = 0.863; p < 0.001) and to the TUG (r = − 0.714; p < 0.001) demonstrated construct validity. Test-rest reliability was measured after an averaged time span of 5.3 ± 2.47 days and resulted in very high reliability [ICC (2,1) = 0.97; p < 0.001]. MDC was 7.57 points for the total score. Conclusion The LCI-5-D is a valid and reliable PROM for measuring mobility with prostheses in German-speaking lower limb amputees, which is rather suitable for people with low to moderate mobility abilities. It can be used in a German-speaking population.
Algal Toxic Compounds and Their Aeroterrestrial, Airborne and other Extremophilic Producers with Attention to Soil and Plant Contamination: A Review

The review summarizes the available knowledge on toxins and their producers from rather disparate algal assemblages of aeroterrestrial, airborne and other versatile extreme environments (hot springs, deserts, ice, snow, caves, etc.) and on phycotoxins as contaminants of emergent concern in soil and plants. There is a growing body of evidence that algal toxins and their producers occur in all general types of extreme habitats, and cyanobacteria/cyanoprokaryotes dominate in most of them. Altogether, 55 toxigenic algal genera (47 cyanoprokaryotes) were enlisted, and our analysis showed that besides the “standard” toxins, routinely known from different waterbodies (microcystins, nodularins, anatoxins, saxitoxins, cylindrospermopsins, BMAA, etc.), they can produce some specific toxic compounds. Whether the toxic biomolecules are related with the harsh conditions on which algae have to thrive and what is their functional role may be answered by future studies. Therefore, we outline the gaps in knowledge and provide ideas for further research, considering, from one side, the health risk from phycotoxins on the background of the global warming and eutrophication and, from the other side, the current surge of interest which phycotoxins provoke due to their potential as novel compounds in medicine, pharmacy, cosmetics, bioremediation, agriculture and all aspects of biotechnological implications in human life.
Stand Out in Class: Investigating the Potential Impact of a Sit–Stand Desk Intervention on Children’s Sitting and Physical Activity during Class Time and after School

Sedentary behaviour (sitting) is a risk factor for adverse health outcomes. The classroom environment has traditionally been associated with prolonged periods of sitting in children. The aim of this study was to examine the potential impact of an environmental intervention, the addition of sit–stand desks in the classroom, on school children’s sitting and physical activity during class time and after school. The ‘Stand Out in Class’ pilot trial was a two-arm cluster randomised controlled trial conducted in eight primary schools with children from a mixed socioeconomic background. The 4.5 month environmental intervention modified the physical (six sit–stand desks replaced standard desks) and social (e.g., teachers’ support) environment. All children wore activPAL and ActiGraph accelerometers for 7 days at baseline and follow-up. In total 176 children (mean age = 9.3 years) took part in the trial. At baseline, control and intervention groups spent more than 65% of class time sitting, this changed to 71.7% and 59.1% at follow-up, respectively (group effect p < 0.001). The proportion of class time spent standing and stepping, along with the proportion of time in light activity increased in the intervention group and decreased in the control group. There was no evidence of any compensatory effects from the intervention after school. Incorporating sit–stand desks to change the classroom environment at primary school appears to be an acceptable strategy for reducing children’s sedentary behaviour and increasing light activity especially during class time. Trial registration: ISRCTN12915848 (registered: 09/11/16).
Mycotoxins Biocontrol Methods for Healthier Crops and Stored Products

Contamination of crops with phytopathogenic genera such as Fusarium, Aspergillus, Alternaria, and Penicillium usually results in mycotoxins in the stored crops or the final products (bread, beer, etc.). To reduce the damage and suppress the fungal growth, it is common to add antifungal substances during growth in the field or storage. Many of these antifungal substances are also harmful to human health and the reduction of their concentration would be of immense importance to food safety. Many eminent researchers are seeking a way to reduce the use of synthetic antifungal compounds and to implement more eco-friendly and healthier bioweapons against fungal proliferation and mycotoxin synthesis. This paper aims to address the recent advances in the effectiveness of biological antifungal compounds application against the aforementioned fungal genera and their species to enhance the protection of ecological and environmental systems involved in crop growing (water, soil, air) and to reduce fungicide contamination of food derived from these commodities.
Connecting With Trauma Patients After Discharge: A Phone Call Follow-Up Study

Background: Traumatic injury is sudden and unexpected. It may lead to long-standing physical and physiological consequences. Approximately 10% of the world's disease burden is attributable to traumatic injuries. At the commencement of the study, there was limited information regarding civilian trauma patients' recovery following discharge from the hospital. There are several reasons for this including lack of available resources for follow-up by clinical staff and often trauma patients have multiple injuries, which can result in fragmented care. This limits the ability to assess a patient's recovery following discharge from the hospital. Objective: This phone call follow-up study was conducted to assess the number of trauma patients who may be showing symptoms of physical and psychological distress after traumatic injury. Methods: The study was carried out in New South Wales (Australia) Metropolitan major (Level 1) trauma center. Consented patients were contacted at 72 hr, 1 month, and 3 months after discharge from the hospital. Results: Many patients at all time points had difficulty coping with activities of daily living from pain (183 patients [64%], 121 patients [43%], and 58 patients [23%]), fatigue and sleep disturbance (110 patients [38%], 79 patients [28%], and 49 patients [20%]), as well as anxiety and frustration (38 patients [13%], 79 patients [28%], and 98 patients [39%]) regarding their recovery and returning to their preinjury activities. Conclusion: The research indicates that some trauma patients do not recover quickly physically or emotionally. These patients require identification and appropriate management of the consequences of trauma to enable them to return to their preinjury quality of life.
Mesoporous Silica-Bioglass Composite Pellets as Bone Drug Delivery System with Mineralization Potential

For decades, local bone drug delivery systems have been investigated in terms of their application in regenerative medicine. Among them, inorganic polymers based on amorphous silica have been widely explored. In this work, we combined two types of amorphous silica: bioglass and doxycycline-loaded mesoporous silica MCM-41 into the form of spherical granules (pellets) as a bifunctional bone drug delivery system. Both types of silica were obtained in a sol-gel method. The drug adsorption onto the MCM-41 was performed via adsorption from concentrated doxycycline hydrochloride solution. Pellets were obtained on a laboratory scale using the wet granulation-extrusion-spheronization method and investigated in terms of physical properties, drug release, antimicrobial activity against Staphylococcus aureus, mineralization properties in simulated body fluid, and cytotoxicity towards human osteoblasts. The obtained pellets were characterized by satisfactory mechanical properties which eliminated the risk of pellets cracking during further investigations. The biphasic drug release from pellets was observed: burst stage (44% of adsorbed drug released within the first day) followed by prolonged release with zero-order kinetics (estimated time of complete drug release was 19 days) with maintained antimicrobial activity. The progressive biomimetic apatite formation on the surface of the pellets was observed. No cytotoxic effect of pellets towards human osteoblasts was noticed.
Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options

Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15–40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.
Non-Penetrance for Ocular Phenotype in Two Individuals Carrying Heterozygous Loss-of-Function ZEB1 Alleles

ZEB1 loss-of-function (LoF) alleles are known to cause a rare autosomal dominant disorder—posterior polymorphous corneal dystrophy type 3 (PPCD3). To date, 50 pathogenic LoF variants have been identified as disease-causing and familial studies have indicated that the PPCD3 phenotype is penetrant in approximately 95% of carriers. In this study, we interrogated in-house exomes (n = 3616) and genomes (n = 88) for the presence of putative heterozygous LoF variants in ZEB1. Next, we performed detailed phenotyping in a father and his son who carried a novel LoF c.1279C>T; p.(Glu427*) variant in ZEB1 (NM_030751.6) absent from the gnomAD v.2. 1.1 dataset. Ocular examination of the two subjects did not show any abnormalities characteristic of PPCD3. GnomAD (n = 141,456 subjects) was also interrogated for LoF ZEB1 variants, notably 8 distinct heterozygous changes presumed to lead to ZEB1 haploinsufficiency, not reported to be associated with PPCD3, have been identified. The NM_030751. 6 transcript has a pLI score ≥ 0.99, indicating extreme intolerance to haploinsufficiency. In conclusion, ZEB1 LoF variants are present in a general population at an extremely low frequency. As PPCD3 can be asymptomatic, the true penetrance of ZEB1 LoF variants remains currently unknown but is likely to be lower than estimated by the familial led approaches adopted to date.