Miracle-dz/UniFAR-FTUs huggingface dataset:
To Use or Not to Use a COVID-19 Contact Tracing App: Mixed Methods Survey in Wales

Background Many countries remain in the grip of the COVID-19 global pandemic, with a considerable journey still ahead toward normalcy and free mobility. Contact tracing smartphone apps are among a raft of measures introduced to reduce spread of the virus, but their uptake depends on public choice. Objective The objective of this study was to ascertain the views of citizens in Wales on their intended use of a COVID-19 contact tracing smartphone app, including self-proposed reasons for or against use and what could lead to a change of decision. Methods We distributed an anonymous survey among 4000 HealthWise Wales participants in May 2020. We adopted a mixed methods approach: responses to closed questions were analyzed using descriptive and inferential statistics; open question responses were analyzed and grouped into categories. Results A total of 976 (24.4%) people completed the survey. Smartphone usage was 91.5% overall, but this varied among age groups. In total, 97.1% were aware of contact tracing apps, but only 67.2% felt sufficiently informed. Furthermore, 55.7% intended to use an app, 23.3% refused, and 21.0% were unsure. The top reasons for app use were as follows: controlling the spread of the virus, mitigating risks for others and for oneself, and increasing freedoms. The top reasons against app use were as follows: mistrusting the government, concerns about data security and privacy, and doubts about efficacy. The top response for changing one’s mind about app use from being willing to being unwilling was that nothing would; that is, they felt that nothing would cause them to become unwilling to use a contact tracing app. This was also the top response for changing one’s mind from being unwilling to being willing to use contact tracing apps. Among those who were unsure of using contact tracing apps, the top response was the need for more information. Conclusions Respondents demonstrated a keenness to help themselves, others, society, and the government to avoid contracting the virus and to control its spread. However, digital inclusion varied among age groups, precluding participation for some people. Nonetheless, unwillingness was significant, and considering the nature of the concerns raised and the perceived lack of information, policy and decision-makers need to do more to act openly, increase communication, and demonstrate trustworthiness if members of the public are to be confident in using an app.
Harmonic Cancellation—A Fundamental of Auditory Scene Analysis

This paper reviews the hypothesis of harmonic cancellation according to which an interfering sound is suppressed or canceled on the basis of its harmonicity (or periodicity in the time domain) for the purpose of Auditory Scene Analysis. It defines the concept, discusses theoretical arguments in its favor, and reviews experimental results that support it, or not. If correct, the hypothesis may draw on time-domain processing of temporally accurate neural representations within the brainstem, as required also by the classic equalization-cancellation model of binaural unmasking. The hypothesis predicts that a target sound corrupted by interference will be easier to hear if the interference is harmonic than inharmonic, all else being equal. This prediction is borne out in a number of behavioral studies, but not all. The paper reviews those results, with the aim to understand the inconsistencies and come up with a reliable conclusion for, or against, the hypothesis of harmonic cancellation within the auditory system.
Modulation of the Physical Properties of 3D Spheroids Derived from Human Scleral Stroma Fibroblasts (HSSFs) with Different Axial Lengths Obtained from Surgical Patients

In the current study, to elucidate the pathological characteristics of myopic scleral stroma, three-dimensional (3D) cultures of human scleral stroma fibroblasts (HSSFs) with several axial lengths (AL, 22.80–30.63 mm) that were obtained from patients (n = 7) were examined. Among the three groups of ALs, <25 mm (n = 2), 25–30 mm (n = 2), and >30 mm (n = 3), the physical properties of the 3D HSSFs spheroids with respect to size and stiffness, the expressions of extracellular matrix (ECM) molecules, including collagen (COL) 1, 4, and 6 and fibronectin (FN) by qPCR and immunohistochemistry (IHC), and the mRNA expression of ECM metabolism modulators including hypoxia-inducible factor 1A (HIF 1A), HIF 2A, lysyl oxidase (LOX), tissue inhibitor of metalloproteinase (TIMP) 1–4, and matrix metalloproteinase (MMP) 2, 9, and 14 as well as several endoplasmic reticulum (ER) stress-related factors were compared. In the largest AL group (>30 mm), the 3D HSSFs spheroids were (1) significantly down-sized and less stiff compared to the other groups, and (2) significant changes were detected in the expression of some ECMs (qPCR; the up-regulation of COL1 and COL4, and the down-regulation of FN, IHC; the up-regulation of COL1 and FN, and down-regulation of COL4). The mRNA expressions of ECM modulators and ER stress-related genes were also altered with increasing AL length (up-regulation of HIF2A, MMP2, XBP1, and MMP14, down-regulation of LOX, TIMP 2 and 3, GRP78, GRP94, IRE1, and ATF6). In addition, a substantial down-regulation of some ER stress-related genes (ATF4, sXPB1 and CHOP) was observed in the 25–30 mm AL group. The findings presented herein suggest that small and stiffer 3D HSSFs spheroids in the largest AL group may accurately replicate the pathological significance of scleral thinning and weakening in myopic eyes. In addition, the modulation of several related factors among the different AL groups may also provide significant insights into our understanding of the molecular mechanisms responsible for causing myopic changes in the sclera.
Rapid 8‐Zone Lung Ultrasound Protocol is Comparable to a Full 12‐Zone Protocol for Outcome Prediction in Hospitalized COVID‐19 Patients

Safety precautions limit the clinical assessment of hospitalized Coronavirus disease 2019 (COVID‐19) patients. The minimal exposure required to perform lung ultrasound (LUS) paired with its high accuracy, reproducibility, and availability make it an attractive solution for initial assessment of COVID‐19 patients. We aim to evaluate whether the association between sonographic findings and clinical outcomes among COVID 19 patients is comparable between the validated 12‐zone protocol and a shorter, 8‐zone protocol, in which the posterior lung regions are omitted.
Environmental conditions drive zooplankton community structure in the epipelagic oceanic water of the southern Gulf of Mexico: A molecular approach

Zooplankton plays a pivotal role in sustaining the majority of marine ecosystems. The distribution patterns and diversity of zooplankton provide key information for understanding the functioning of these ecosystems. Nevertheless, due to the numerous cryptic and sibling species and the lack of diagnostic characteristics for early developmental stages, the identification of the global‐to‐local patterns of zooplankton biodiversity and biogeography remains challenging in different research fields. The spatial and temporal changes in the zooplankton community in the open waters of the southern Gulf of Mexico were assessed using metabarcoding analysis of the V9 region of 18S rRNA and mitochondrial cytochrome oxidase c subunit I (COI). Additionally, a multiscale analysis was implemented to evaluate which environmental predictors may explain the variability in the structure of the zooplankton community. Our findings suggest that the synergistic effects of dissolved oxygen concentration, temperature, and longitude (intended as a proxy for still unidentified predictors) may explain both spatial and temporal zooplankton variability even with low contribution. Furthermore, the zooplankton distribution probably reflects the coexistence of three heterogeneous ecoregions and a bio‐physical partitioning of the studied area. Finally, some taxa were either exclusive or predominant with either 18S or COI markers. This may suggest that comprehensive assessments of the zooplankton community may be more accurately met by the use of multilocus approaches.
Antisense Oligonucleotide-Mediated Silencing of Mitochondrial Fusion and Fission Factors Modulates Mitochondrial Dynamics and Rescues Mitochondrial Dysfunction

Mitochondria are highly dynamic organelles that produce ATP and maintain metabolic, catabolic, and redox homeostasis. Mitochondria owe this dynamic nature to their constant fission and fusion—processes that are regulated, in part, by fusion factors (MFN1 and MFN2) and fission factors (DRP1, FIS1, MFF, MIEF1, MIEF2) located on the outer mitochondrial membrane. While mitochondrial fusion and fission are known to influence mitochondrial morphology and function, a key question is whether rebalancing mitochondrial morphology can ameliorate mitochondrial dysfunction in the context of mitochondrial pathology. In this study, we used antisense oligonucleotides (ASOs) to systematically evaluate the effects of fusion and fission factors in vitro. Free uptake by cells of fusion or fission factor ASOs caused robust decreases in target gene expression and altered a variety of mitochondrial parameters, including mitochondrial size and respiration, which were dose dependent. In Mfn1 knockout mouse embryonic fibroblasts (MEFs) and MFN2-R94Q (Charcot-Marie-Tooth Type 2 Disease-associated mutation) MEFs, two cellular models of mitochondrial dysfunction, we found that ASO-mediated silencing of only Drp1 restored mitochondrial morphology and enhanced mitochondrial respiration. Together, these data demonstrate in vitro proof-of-concept for rebalancing mitochondrial morphology to rescue function using ASOs and suggest that ASO-mediated modulation of mitochondrial dynamics may be a viable therapeutic approach to restore mitochondrial homeostasis in diseases driven by mitochondrial dysfunction.
Differential expression of circulating microRNAs in serum: Potential biomarkers to track Japanese encephalitis virus infection

Japanese encephalitis is one of the serious vector‐borne viral encephalitis diseases found worldwide and poses a major threat to public health. Most Japanese encephalitis virus (JEV) infections are subclinical; only 1: 250 to 1:1000 infected persons develop clinical presentations. Delay in proper diagnosis of JE affects the timeliness of treatment initiation and increases the mortality rate in patients. Therefore, there is an extreme need to develop potential biomarkers, which might improve the diagnosis and can become the basis for development of new therapeutics. The microRNAs (miRNAs/or miRs) are small noncoding RNAs of 17–24 nucleotides that are known to regulate about 60% of human genes. Although miRNAs have been found to regulate various aspects of innate and adaptive immune responses, less information on circulating miRNAs in JE is known. The study of JEV infected human serum miRNAs will provide novel information for the diagnosis of JE as well as for the improvement of disease outcome.
PD‐1 inhibitors for cutaneous squamous cell carcinoma: A meta‐analysis

PD‐1 inhibitors are immunotherapeutic agents used in the treatment of advanced cutaneous squamous cell carcinoma (cSCC). This study aimed to determine the pooled objective response and disease control rates of patients with advanced cSCC treated with PD‐1 inhibitors. Pubmed, Cochrane Library and EMBASE databases were searched up to 1 January 2021 to include eligible articles. Objective response rate (ORR) and disease control rate (DCR) were pooled and analysed. Subgroup analysis of the odds ratio (OR) for ORR for patients by PD‐L1 tumour proportion score (TPS) was performed. Seven articles including a total of 453 patients were identified and included. Pooled estimate of ORR was 44% (95% CI: 39‐49%, I2 = 23.7%) and of DCR was 66% (95% CI: 57‐74%, I2 = 68.2%). Pooled odds ratio of ORR for patients by PD‐L1 TPS was 2.81 (95% CI: 1.22‐6.51, I2 = 0.0%). These results were derived from single‐arm studies, some of which were retrospective. No head‐to‐head trials comparing PD‐1 inhibitors have been reported. We present aggregate estimates of ORR and DCR for patients with advanced cSCC treated with PD‐1 inhibitors, as well as subgroup analysis for ORR for patients by PD‐L1 TPS.
“What I couldn’t do before, I can do now”: Narrations of agentic shifts and psychological growth by young adults reporting discontinuation of self-injury since adolescence

ABSTRACT Purpose We explore young adults’ narrations of life events in association with nonsuicidal self-injury (NSSI) discontinuation, psychological growth, and agency. Methods Transcripts from eleven face-to-face interviews with individuals who quantitatively reported injuring themselves in adolescence (2007–2008) but not in young adulthood (2017) were narratively analysed. Results We found that at starting points, a period preceding an agentic shift in the narrative, participants endured stressful living conditions and mental illness. During this period, participants perceived no point in trying to initiate change because they did not perceive themselves as having the capacity to do so and nor could they adequately utilize any formal or informal support. After a turning point that enabled agency due to gaining a sense of belongingness, liberation, or perspective, participants underwent a process of attaining psychological well-being. However, narrating psychological growth also required momentum points, encompassing the management of and moving on from stressful contexts, along with the recognition of milestones marking improvement relative to the starting points. Conclusions NSSI discontinuation was narrated in conjunction with psychological growth when participants also experienced themselves as situated within an agentic context, because agency is understood as necessary to react to and manage current and future life circumstances.
Outcomes of staged reconstruction of Zone 2 flexor tendon injuries in recent wide-awake surgical settings and an earlier case series

We report outcomes of patients who were managed with two-stage tendon grafting for neglected Zone 2 flexor tendon injuries from 2012 until 2019. The patients were divided into two cohorts: recent series (Series 1) included patients treated with local anaesthesia and epinephrine (16 fingers, from 2015), and earlier series (Series 2) included patients treated with either general or local intravenous anaesthesia and tourniquet (12 fingers, before 2015). The patients in Series 1 achieved statistically better mean total active motion of the operated fingers and grip compared with the contralateral hand than the earlier series (p = 0.03, p = 0.01, respectively). With the Tang grading system, excellent and good results were achieved in 13 and six fingers of the patients in Series 1 and Series 2, respectively. We conclude that wide-awake second stage of staged flexor tendon grafting provides fine-tuned adjustment of length and tension of the graft, but we cannot conclude about comparative outcomes between two series because the sample size is small and the earlier series was operated by the same surgeons with lower expertise level. Level of evidence: IV
Pathogenic mechanisms of preeclampsia with severe features implied by the plasma exosomal mirna profile

ABSTRACT Preeclampsia is a complication of pregnancy characterized by high blood pressure and organ damage after 20 gestational weeks. It is associated with high maternal and fetal morbidity and mortality. However, at present, there is no effective prevention or treatment for this condition. Previous studies have revealed that plasma exosomal mirnas from pregnant women with preeclampsia could serve as biomarkers of pathogenic factors. However, the roles of plasma exosomal mirnas in preeclampsia with severe features (sPE), which is associated with poorer pregnancy outcomes, remain unknown. Thus, the aims of this study were to characterize plasma exosomal miRNAs in sPE and explore the related pathogenic mechanisms using bioinformatic analysis. Plasma exosomes were isolated using a mirVana RNA isolation kit. the exosomal miRNAs were detected using high-throughput sequencing and the mirnas related to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) terms were analyzed using the clusterprofiler package of R. Fifteen miRNAs exhibited increased expression and fourteen miRNAs exhibited reduced expression in plasma exosomes from women with sPE as compared to normal pregnant women. Further, gene set enrichment analysis revealed that the differentially expressed plasma exosomal miRNAs were related to the stress response and cell junction regulation, among others. In summary, this study is the first to identify the differentially expressed plasma exosomal miRNAs in sPE. These findings highlight promising pathogenesis mechanisms underlying preeclampsia.
Visual pursuit behavior in mice maintains the pursued prey on the retinal region with least optic flow

Mice have a large visual field that is constantly stabilized by vestibular ocular reflex (VOR) driven eye rotations that counter head-rotations. While maintaining their extensive visual coverage is advantageous for predator detection, mice also track and capture prey using vision. However, in the freely moving animal quantifying object location in the field of view is challenging. Here, we developed a method to digitally reconstruct and quantify the visual scene of freely moving mice performing a visually based prey capture task. By isolating the visual sense and combining a mouse eye optic model with the head and eye rotations, the detailed reconstruction of the digital environment and retinal features were projected onto the corneal surface for comparison, and updated throughout the behavior. By quantifying the spatial location of objects in the visual scene and their motion throughout the behavior, we show that the prey image consistently falls within a small area of the VOR-stabilized visual field. This functional focus coincides with the region of minimal optic flow within the visual field and consequently area of minimal motion-induced image-blur, as during pursuit mice ran directly toward the prey. The functional focus lies in the upper-temporal part of the retina and coincides with the reported high density-region of Alpha-ON sustained retinal ganglion cells.
Transcription profiling of cadmium-exposed livers reveals alteration of lipid metabolism and predisposition to hepatic steatosis

Abstract 1. Cadmium (Cd) is a ubiquitous environmental toxicant that can cause liver steatosis and nonalcoholic fatty liver disease (NAFLD) on long-term exposure. 2. Sixteen Sprague Dawley rats were randomly divided into two groups, and were administered normal saline and 5 mg/(kg·d) cadmium chloride by gavage. In vitro, BRL3A cells, a rat normal liver cell line, were treated with different concentrations of Cd to verify the sequencing results. 3. The RNA-seq revealed 146 upregulated genes and 127 downregulated genes in the Cd intervention group. The key genes of lipid metabolism were significantly overexpressed, such as Cyp1a1 and Pla2g2d. The GO enrichment analysis showed that the ‘sterol biosynthetic process’ was the most obvious difference. The KEGG analysis showed that six of the top 10 differential pathways were related to lipid metabolism. The expression of the essential genes in BRL3A was consistent with the sequencing results. The protein–protein interaction (PPI) yielded that Cyp1a1 is in the central region of the differentially expressed gene network. 4. The chronic Cd exposure is still an important environmental health problem with a probable tendency to cause NAFLD. It may possibly act by affecting the lipid metabolism in the liver, especially the synthesis and decomposition of unsaturated fatty acids.
Antitumorigenic effect of combination treatment with ONC201 and TRAIL in endometrial cancer in vitro and in vivo

ABSTRACT ONC201 demonstrated promising activity in patients with advanced endometrial cancer in a Phase I clinical trial. ONC201 activates the integrated stress response (ISR) and upregulates TRAIL and its receptor DR5. We hypothesized ONC201 upregulation of DR5 could sensitize tumors to TRAIL and combination of ONC201 and TRAIL would lead to enhanced cell death in endometrial cancer models. Five endometrial cancer cell lines AN3CA, HEC1A, Ishikawa, RL952, and KLE as well as a murine xenograft model were treated with ONC201 alone or in combination with TRAIL. ONC201 decreased the cell viability of all five endometrial cancer cell lines at clinically achievable low micro-molar concentrations (2–4 μM). ONC201 activated the ISR and induced protein expression of TRAIL and DR5 at the cell surface. Pretreatment with ONC201 sensitized endometrial cancer cell lines to TRAIL, leading to increased cell death induction compared to either agent alone. Tumor growth was reduced in vivo by the ONC201/TRAIL combination treatment in the xenograft model of endometrial cancer (p = .014). Mice treated with combination treatment survived significantly longer than mice from the three control groups (p = .018). ONC201 decreased cell viability in endometrial cancer cells lines primarily through growth arrest while the combination of ONC201 and TRAIL promoted cell death in vitro and in vivo. Our results suggest a novel cancer therapeutic strategy that can be further investigated in the clinic.
Evaluation of the Neuroprotective Effects of Methylprednisolone and Surgical Decompression in a Rodent Model of Traumatic Optic Neuropathy

ABSTRACT Purpose of the study Traumatic optic neuropathy (TON) is a rare but serious consequence of head injuries. The optimal therapy for TON remains controversial, and standardized recommendations are lacking. The most common therapies used are steroid administration and surgical decompression procedures. The aim of the present study was to compare two common conservative and surgical therapies in a rodent model with a standardized traumatic optic nerve lesion. Materials and Methods This study employed 59 male Wistar rats. After exposing the optic nerve, defined trauma was exerted on the optic nerve using a micromanipulator to trigger TON. Rats received either “megadose” methylprednisolone applied perioperatively or decompression via nerve sheath fenestration. The number of neurons was histologically evaluated in retinae explanted as whole mounts. Neuronal size was determined histomorphometrically. Results Neuronal loss was significantly lower following perioperative “megadose” steroid therapy (p = .017), especially in the central retinal area (p = .025). Compared to the control group without therapy, on average more than 400 neurons/mm2 were saved. In the central retinal area, more than 600 neurons/mm2 were rescued. In contrast, neuronal loss was not significantly affected by surgical decompression; however, this procedure was associated with a reduction in neuron size (p = .003). Conclusions The present model revealed significant neuroprotective effects following administration of methylprednisolone for TON treatment. Mitigation of neuronal loss may result in functional benefits. Neuroprotective effects were not observed following surgical therapy, suggesting that this approach should be reserved for individual cases such as hematomas in the area of nerve envelopes.