Miracle-dz/UniFAR-FTUs huggingface dataset:
Human DLG1 and SCRIB Are Distinctly Regulated Independently of HPV-16 during the Progression of Oropharyngeal Squamous Cell Carcinomas: A Preliminary Analysis

Simple Summary The process of HPV-mediated oncogenesis in HNSCCs is not fully understood. DLG1 and SCRIB protein expression levels and localization changes were evaluated in a number of HPV16-positive and HPV-negative OPSCCs and seem to be associated with malignant transformation. Moreover, loss of SCRIB expression inversely correlates with higher grade tumors, and this is much more evident in the presence of HPV16 E6. This could serve as a potential marker in predicting development of OPSCCs. Abstract The major causative agents of head and neck squamous cell carcinomas (HNSCCs) are either environmental factors, such as tobacco and alcohol consumption, or infection with oncogenic human papillomaviruses (HPVs). An important aspect of HPV-induced oncogenesis is the targeting by the E6 oncoprotein of PDZ domain-containing substrates for proteasomal destruction. Tumor suppressors DLG1 and SCRIB are two of the principal PDZ domain-containing E6 targets. Both have been shown to play critical roles in the regulation of cell growth and polarity and in maintaining the structural integrity of the epithelia. We investigated how modifications in the cellular localization and protein expression of DLG1 and SCRIB in HPV16-positive and HPV-negative histologic oropharyngeal squamous cell carcinomas (OPSCC) might reflect disease progression. HPV presence was determined by p16 staining and HPV genotyping. Whilst DLG1 expression levels did not differ markedly between HPV-negative and HPV16-positive OPSCCs, it appeared to be relocated from cell–cell contacts to the cytoplasm in most samples, regardless of HPV16 positivity. This indicates that alterations in DLG1 distribution could contribute to malignant progression in OPSCCs. Interestingly, SCRIB was also relocated from cell–cell contacts to the cytoplasm in the tumor samples in comparison with normal tissue, regardless of HPV16 status, but in addition there was an obvious reduction in SCRIB expression in higher grade tumors. Strikingly, loss of SCRIB was even more pronounced in HPV16-positive OPSCCs. These alterations in SCRIB levels may contribute to transformation and loss of tissue architecture in the process of carcinogenesis and could potentially serve as markers in the development of OPSCCs.
Impairment in renal medulla development underlies salt wasting in Clc-k2 channel deficiency

The prevailing view is that the ClC-Ka chloride channel (mouse Clc-k1) functions in the thin ascending limb to control urine concentration, whereas the ClC-Kb channel (mouse Clc-k2) functions in the thick ascending limb (TAL) to control salt reabsorption. Mutations of ClC-Kb cause classic Bartter syndrome, characterized by renal salt wasting, with perinatal to adolescent onset. We studied the roles of Clc-k channels in perinatal mouse kidneys using constitutive or inducible kidney-specific gene ablation and 2D and advanced 3D imaging of optically cleared kidneys. We show that Clc-k1 and Clc-k2 were broadly expressed and colocalized in perinatal kidneys. Deletion of Clc-k1 and Clc-k2 revealed that both participated in NKCC2- and NCC-mediated NaCl reabsorption in neonatal kidneys. Embryonic deletion of Clc-k2 caused tubular injury and impaired renal medulla and TAL development. Inducible deletion of Clc-k2 beginning after medulla maturation produced mild salt wasting resulting from reduced NCC activity. Thus, both Clc-k1 and Clc-k2 contributed to salt reabsorption in TAL and distal convoluted tubule (DCT) in neonates, potentially explaining the less-severe phenotypes in classic Bartter syndrome. As opposed to the current understanding that salt wasting in adult patients with Bartter syndrome is due to Clc-k2 deficiency in adult TAL, our results suggest that it originates mainly from defects occurring in the medulla and TAL during development.
The Impact of an Authoritarian Personality on Pro-Environmental Behaviour for Air Pollution Mitigation through Interactions with Social Norms

This study examines how risk perception and authoritarian personality affect public engagement in mitigating air pollution. Data were collected (n = 2010) from 13 Chinese cities with varying air pollution gradients using questionnaires. The results demonstrated that air pollution was significantly correlated with people’s risk perception and concern about air pollution, which significantly affected their pro-environmental behaviour (PEB). However, high-risk perceptions undermine the public’s self-efficacy and reduce people’s PEB in the private sphere. People with high scores of the authoritarian personality type were reluctant to engage in PEB in the private sphere; interestingly, it can also be transformed into a stronger PEB in the public sphere via social norms. Thus, this study suggests that educational activities can break the negative link between authoritarianism and environmentalism, leading to behavioural change. Hence, it is essential for education programs to harvest positive outcomes via adaptive approaches for varying authoritarian personalities.
Quantification of the Psychoacoustic Effect of Noise from Small Unmanned Aerial Vehicles

This paper presents the results of a study evaluating the human perception of the noise produced by four different small quadcopter unmanned aerial vehicles (UAVs). This study utilised measurements and recordings of the noise produced by the quadcopter UAVs in hover and in constant-speed flight at a fixed altitude. Measurements made using a ½″ microphone were used to calculate a range of different noise metrics for each noise event. Noise recordings were also made using a spherical microphone array (an Eigenmike system). The recordings were reproduced using a 3D sound reproduction system installed in a large anechoic chamber located at The University of Auckland. Thirty-seven participants were subjected to the recordings and asked to rate their levels of annoyance in response to the noise, and asked to perform a simple cognitive task in order to assess the level of distraction caused by the noise. This study discusses the noise levels measured during the test and how the various noise metrics relate to the annoyance ratings. It was found that annoyance strongly correlates with the sound pressure level and loudness metrics, and that there is a very strong correlation between the annoyance caused by a UAV in hover and in flyby at the same height. While some significant differences between the distraction caused by the UAV noise for different cases were observed in the cognitive distraction test, the results were inconclusive. This was likely due to a ceiling effect observed in the participants’ test scores.
Feasibility of a Smoking Cessation Smartphone App (Quit with US) for Young Adult Smokers: A Single Arm, Pre-Post Study

While smartphone applications (apps) have been shown to enhance success with smoking cessation, no study has been conducted among young adult smokers aged 18–24 years in Thailand. Quit with US was developed based on the 5 A’s model and self-efficacy theory. This single arm, pre-post study was conducted aiming to assess results after using Quit with US for 4 weeks. The primary outcome was a biochemically verified 7-day point prevalence of smoking abstinence. The secondary outcomes included smoking behaviors, knowledge and attitudes toward smoking and smoking cessation, and satisfaction and confidence in the smartphone app. A total number of 19 young adult smokers were included; most participants were males (68.4%) with the mean (SD) age of 20.42 (1.46) years. After 4 weeks of study, the primary outcome demonstrated a smoking cessation rate of 31.6%. All 19 participants expressed better smoking behaviors and better knowledge and attitudes toward smoking and smoking cessation. Further, they were satisfied with the smartphone app design and content and expressed confidence in using it. These findings provided preliminary evidence that Quit with US was found to be a potentially effective smoking cessation smartphone app for young adult smokers.
Oral Microbiota Features in Subjects with Down Syndrome and Periodontal Diseases: A Systematic Review

Down syndrome (DS) is a genetic disorder associated with early-onset periodontitis and other periodontal diseases (PDs). The present work aimed to systematically review the scientific literature reporting studies in vivo on oral microbiota features in subjects with DS and related periodontal health and to highlight any correlation and difference with subjects not affected by DS, with and without PDs. PubMed, Web of Science, Scopus and Cochrane were searched for relevant studies in May 2021. The participants were subjects affected by Down syndrome (DS) with and without periodontal diseases; the study compared subjects with periodontal diseases but not affected by DS, and DS without periodontal diseases; the outcomes were the differences in oral microbiota/periodontopathogen bacterial composition among subjects considered; the study design was a systematic review. Study quality was assessed with risk of bias in non-randomized studies of interventions (ROBINS-I). Of the 954 references retrieved, 26 studies were considered. The conclusions from the qualitative assessment of the papers revealed an increasing knowledge over the last years of the microbiota associated with DS and their periodontal diseases, in comparison with healthy subjects and subjects with other kinds of mental disabilities. Few data have emerged on the mycobiome and virobiome of DS, hence, further investigations are still necessary.
Intravitreal Dexamethasone Implants for Refractory Macular Edema in Eyes with Noninfectious Uveitis

Macular edema (ME) is a common cause of visual loss among eyes with uveitis, and its management can be challenging. Steroids are an effective treatment for ME, and intravitreal dexamethasone (DEX) implants provide sustained steroid release. The purpose of this study is to evaluate intravitreal DEX implant on refractory ME in eyes with noninfectious uveitis. A retrospective study including 52 eyes of 37 patients with refractory uveitic ME was conducted from January 2011 through August 2017 at Linkou Chang Gung Memorial Hospital in Taiwan. Patients’ demographic characteristics were collected. In addition, clinical information, including corrected visual acuity (VA), intraocular pressure (IOP), and central retinal thickness (CRT) on optical coherence tomography, was recorded and analyzed. During the study period, affected eyes received a total of 110 intravitreal DEX implants (range, one to six in each eye). After the first DEX implant injection in all eyes, VA significantly improved at one and two months. CRT significantly decreased one month after a single DEX implant, and the effect lasted for six months and waned over time. Patients receiving multiple DEX implants still showed significant decreases in CRT one month after the first implant. Increases in IOP were noted one month after the DEX implant, but the IOP could be medically controlled. Intravitreal DEX implants can effectively treat refractory uveitic ME, improving both VA and CRT with an acceptable safety profile. Further studies are necessary to evaluate the effect of multiple implants and long-term outcomes.
Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis

Background and Objectives To investigate the potential of serum neurofilament light (NfL) to reflect or predict progression mostly independent of acute inflammatory disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab. Methods Patients were selected from a prospective observational cohort study initiated in 2006 at the VU University Medical Center Amsterdam, the Netherlands, including patients with RRMS treated with natalizumab. Selection criteria included an age of 18 years or older and a minimum follow-up of 3 years from natalizumab initiation. Clinical and MRI assessments were performed on a yearly basis, and serum NfL was measured at 5 time points during the follow-up, including on the day of natalizumab initiation (baseline), 3 months, 1 year, and 2 years after natalizumab initiation, and on last follow-up visit. Using general linear regression models, we compared the longitudinal dynamics of NfL between patients with and without confirmed Expanded Disability Status Scale (EDSS) progression between year 1 visit and last follow-up, and between individuals with and without EDSS+ progression, a composite endpoint including the EDSS, 9-hole peg test, and timed 25-foot walk. Results Eighty-nine natalizumab-treated patients with RRMS were included. Median follow-up time was 5.2 years (interquartile range [IQR] 4.3–6.7, range 3.0–11.0) after natalizumab initiation, mean age at time of natalizumab initiation was 36.9 years (SD 8.5), and median disease duration was 7.4 years (IQR 3.8–12.1). Between year 1 and the last follow-up, 28/89 (31.5%) individuals showed confirmed EDSS progression. Data for the EDSS+ endpoint was available for 73 out of the 89 patients and 35/73 (47.9%) showed confirmed EDSS+ progression. We observed a significant reduction in NfL levels 3 months after natalizumab initiation, which reached its nadir of close to 50% of baseline levels 1 year after treatment initiation. We found no difference in the longitudinal dynamics of NfL in progressors vs nonprogressors. NfL levels at baseline and 1 year after natalizumab initiation did not predict progression at last follow-up. Conclusion In our cohort of natalizumab-treated patients with RRMS, NfL fails to capture or predict progression that occurs largely independently of clinical or radiologic signs of acute focal inflammatory disease activity. Additional biomarkers may thus be needed to monitor progression in these patients. Classification of Evidence This study provides Class II evidence that serum NfL levels are not associated with disease progression in natalizumab-treated patients with RRMS.
Characterization of Protocatechuate 4,5-Dioxygenase from Pseudarthrobacter phenanthrenivorans Sphe3 and In Situ Reaction Monitoring in the NMR Tube

The current study aims at the functional and kinetic characterization of protocatechuate (PCA) 4,5-dioxygenase (PcaA) from Pseudarthrobacter phenanthrenivorans Sphe3. This is the first single subunit Type II dioxygenase characterized in Actinobacteria. RT-PCR analysis demonstrated that pcaA and the adjacent putative genes implicated in the PCA meta-cleavage pathway comprise a single transcriptional unit. The recombinant PcaA is highly specific for PCA and exhibits Michaelis–Menten kinetics with Km and Vmax values of 21 ± 1.6 μM and 44.8 ± 4.0 U × mg−1, respectively, in pH 9.5 and at 20 °C. PcaA also converted gallate from a broad range of substrates tested. The enzymatic reaction products were identified and characterized, for the first time, through in situ biotransformation monitoring inside an NMR tube. The PCA reaction product demonstrated a keto-enol tautomerization, whereas the gallate reaction product was present only in the keto form. Moreover, the transcriptional levels of pcaA and pcaR (gene encoding a LysR-type regulator of the pathway) were also determined, showing an induction when cells were grown on PCA and phenanthrene. Studying key enzymes in biodegradation pathways is significant for bioremediation and for efficient biocatalysts development.
First-Trimester Screening for Gestational Diabetes Mellitus in Twin Pregnancies

We previously reported a logistic regression model for prediction of GDM from maternal characteristics and medical history in 75,161 singleton pregnancies. In this study of 1376 twin and 13,760 singleton pregnancies recruited at 11–13 weeks’ gestation, we extend the model to include terms for twin pregnancies. We found the respective odds of GDM in dichorionic and monochorionic twin pregnancies to be 1.36 (95% CI: 1.02–1.81) and 2.78 (95% CI: 1.72–4.48) times higher than in singleton pregnancies. In both singleton and twin pregnancies, the risk for GDM increased with maternal age and weight and birth weight z-score of a baby in a previous pregnancy and is higher in women with a previous pregnancy complicated by GDM; in those with a first- or second-degree relative with diabetes mellitus; in women of Black, East Asian, and South Asian racial origin; and in pregnancies conceived through the use of ovulation-induction drugs. In singleton pregnancies, at 10% and 20% false-positive rate, the detection rate was 43% and 58%, respectively. In twin pregnancies, using risk cut-offs corresponding to 10% and 20% false-positive rates in singletons, the respective false-positive rates were 27% and 47%, and the detection rates were 63% and 81%.
Germline CDH1 G212E Missense Variant: Combining Clinical, In Vitro and In Vivo Strategies to Unravel Disease Burden

Simple Summary Hereditary diffuse gastric cancer (HDGC) is an inherited cancer syndrome associated with CDH1 germline mutations. The increasing detection of CDH1 genetic variants due to multigene panel testing poses a serious clinical challenge and urges the development of effective classification strategies. In this study, we describe the identification of the novel CDH1 G212E variant in a large family strongly affected by diffuse gastric cancer. Through a comprehensive characterization pipeline, we provide evidence of the damaging nature of this genetic alteration, thus impacting patient management and family screening. Abstract E-cadherin, encoded by CDH1, is an essential molecule for epithelial homeostasis, whose loss or aberrant expression results in disturbed cell–cell adhesion, increased cell invasion and metastasis. Carriers of CDH1 germline mutations have a high risk of developing diffuse gastric cancer and lobular breast cancer, associated with the cancer syndrome Hereditary Diffuse Gastric Cancer (HDGC). The ubiquitous availability of cancer panels has led to the identification of an increasing amount of “incidental” CDH1 genetic variants that pose a serious clinical challenge. This has sparked intensive research aiming at an accurate classification of the variants and consequent validation of their clinical relevance. The present study addressed the significance of a novel CDH1 variant, G212E, identified in an unusually large pedigree displaying strong aggregation of diffuse gastric cancer. We undertook a comprehensive pipeline encompassing family data, in silico predictions, in vitro assays and in vivo strategies, which validated the deleterious phenotype induced by this genetic alteration. In particular, we demonstrated that the G212E variant affects the stability and localization, as well as the adhesive and anti-invasive functions of E-cadherin, triggering epithelial disruption and disorganization. Our findings illustrate the clinical implication of a complementary approach for effective variant categorization and patient management.
Rituximab Induction and Maintenance in ANCA-Associated Vasculitis: State of the Art and Future Perspectives

Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the vascular wall. The pathogenesis of AAV is strongly associated with B cell-derived ANCAs; thus, Rituximab (RTX) has become a promising drug in the induction and maintenance treatment of AAV. The purpose of this review is to describe the efficacy and safety of RTX in the induction of remission and maintenance therapy of AAV. Herein, we summarize the randomized controlled trials that have contributed to the refinement of the use of RTX in AAV in the past decades. RTX has been proven to be effective both in new-onset disease and in relapsing disease. Although the optimal duration of AAV maintenance therapy remains unknown, the ANCAs and the B-cell repopulation may offer support for the administration of further RTX cycles (or not). The safety of RTX is comparable with cyclophosphamide, with the advantage of a low risk of malignancy and no concern for fertility. In conclusion, RTX now plays an important role in the induction and maintenance therapy of AAV. Optimizing RTX-based treatment strategies in AAV is one of the main goals of the current research in AAV.
Psychological States and Training Habits during the COVID-19 Pandemic Lockdown in Spanish Basketball Athletes

The outbreak of the COVID-19 pandemic and the resulting restrictions designed to slow the spread of infection greatly disrupted people’s lives. The present study aimed to investigate the impact of lockdown on the psychology, training, and sleep habits of a cohort of basketball players. An online survey involving 169 professional and amateur athletes was conducted using four validated psychological questionnaires (WLEIS-S, POMS, BRS, SMS-II) and a Likert scale to measure the rating of perceived exertion (RPE) and training variables. Gender differences in fatigue (p = 0.022); friendships (p = 0.017); others’ emotional appraisal (p < 0.001); and resilience (p = 0.031) were apparent, with higher values for women in all categories bar resilience. Comparisons before and during the lockdown revealed that all participants reduced their RPE (p < 0.001); training days (p = 0.004); and training hours (p < 0.001), and experienced a decline in the quality of sleep (p < 0.001). Sleep hours (p < 0.001) increased during lockdown. The professionals and females maintained their training days (p > 0.05), while the non-professionals and males did not. Psychological states during lockdown were a predictor of the differences in training and recovery variables. In situations where training and competition are limited, it is important to develop plans to maintain physical activity, good quality sleep, and promote greater emotional management and understanding to control negative moods.
Fabrication of Vertical-Standing Co-MOF Nanoarrays with 2D Parallelogram-like Morphology for Aqueous Asymmetric Electrochemical Capacitors

Metal organic frameworks (MOFs) have been considered as one of the most promising electrode materials for electrochemical capacitors due to their large specific surface area and abundant pore structure. Herein, we report a Co-MOF electrode with a vertical-standing 2D parallelogram-like nanoarray structure on a Ni foam substrate via a one-step solvothermal method. The as-prepared Co-MOF on a Ni foam electrode delivered a high area-specific capacitance of 582.0 mC cm−2 at a current density of 2 mA cm−2 and a good performance rate of 350.0 mC cm−2 at 50 mA cm−2. Moreover, an asymmetric electrochemical capacitor (AEC) device (Co-MOF on Ni foam//AC) was assembled by using the as-prepared Co-MOF on a Ni foam as the cathode and a active carbon-coated Ni foam as the anode to achieve a maximum energy density of 0.082 mW cm−2 at a power density of 0.8 mW cm−2, which still maintained 0.065 mW cm−2 at a high power density of 11.94 mW cm−2. Meanwhile, our assembled device exhibited an excellent cycling stability with a capacitance retention of nearly 100% after 1000 cycles. Therefore, this work provides a simple method to prepare MOF-based material for the application of energy storage and conversion.