Validation of the Polish version of the Hand Function Scoring system.

BACKGROUND: The Hand Function Scoring (HFS) system was created to assess the results of rehabilitation treatment after hand injuries. A perceived hand function improvement in patients who underwent carpal tunnel syndrome surgery prompted us to use the Watts HFS questionnaire in our study. OBJECTIVES: The study aimed to: 1) translate and validate the new questionnaire into Polish; 2) analyze the usefulness of the scale in the preand post-operative assessment of patients with carpal tunnel syndrome; and 3) compare the results with other questionnaires recognized as the gold standard in carpal tunnel treatment evaluation. MATERIAL AND METHODS: Patients with electromyographically confirmed carpal tunnel syndrome (n = 317) were enrolled in the study. Participants completed the HFS, Boston Carpal Tunnel Questionnaire (BCTQ), Michigan Hand Outcomes Questionnaire (MHQ), and the Quality-of-Life Scale (QoLS) on their first visit to our clinic. Two weeks later, 84 patients completed the same questionnaires again, and 6-12 months after the operation, we received 90 additional responses. RESULTS: The analysis showed that the HFS questionnaire met the validation criteria and had a strong correlation with the BCTQ questionnaire for the Symptoms Severity Scale (SSS) (Rho = 0.70, p < 0.001) and the Functional Status Scale (FSS) (Rho = 0.89, p < 0.001). CONCLUSIONS: The HFS questionnaire was successfully employed in the subjective assessment of carpal tunnel symptom syndrome severity and the analysis of treatment results, and would complement the clinical assessment of patients during treatment. The questionnaire could also be used in future scientific research.

Optoelectronic and photocatalytic behaviour of a type-II GaAlS2/HfS2heterostructure:ab initiostudy.

Theoretical examination based on first principle computation has been conducted for van der Waals heterostructure (vdwHS) GaAlS2/HfS2including structural, optoelectronic and photocatalytic characteristics. From the adhesion energy calculation, the AB configuration of GaAlS2/HfS2vdwHS is the most stable. A type-II GaAlS2/HfS2vdwHS is a dynamically and thermally stable structure. The band edge position, projected band, and projected charge densities verify the type-II alignment of GaAlS2/HfS2vdwHS. For GaAlS2/HfS2, GaAlS2is acting as a donor and HfS2is acting as an acceptor ensured by the charge density difference plot. The electron localized function validates the weak van der Waals interaction between GaAlS2and HfS2. The GaAlS2/HfS2vdwHS possess an indirect bandgap of 1.54 eV with notable absorption in the visible range. The findings assure that the GaAlS2/HfS2vdwHS is an efficient photocatalyst for pH 4-8. The band alignment of GaAlS2/HfS2is suitable for Z-scheme charge transfer. The strain influenced band edge suggests that the GaAlS2/HfS2vdwHS remains photocatalytic for strain-4%to+6%in both cases of uniaxial and biaxial strains.

Impact of Botulinum Toxin Injections on Quality of Life of Patients with Long-Standing Peripheral Facial Palsy.

(1) Background: Sequels of facial palsy lead to major psychosocial repercussions, disrupting patients' quality of life (QoL). Botulinum toxin (BoNT) injections can permit us to treat long-standing facial palsy, improving facial symmetry and functional signs including synkinesis and contractures. (2) Methods: The main aim of this study was to assess the evolution of the QoL for patients with long-standing facial palsy before, at 1 month, and at 4 months after BoNT injections by using three questionnaires (HFS-30, FaCE, and HAD). The other goals were to find clinical factors associated with the improvement in the QoL and to assess the HFS-30 questionnaire for patients with unilateral facial palsy (3) Results: Eighty-eight patients were included in this study. There was a statistically significant improvement in QoL at 1 month after injections, assessed using the three questionnaires. This improvement was sustained at 4 months after the injections, with a statistically significant difference for the HFS-30 and FaCE questionnaires. (4) Conclusions: This study showed that the BoNT injections lead to a significant increase in the QoL of patients with unilateral facial palsy. This improvement is sustained 4 months after the injections.

Ganglionated Plexus Ablation Procedures to Treat Vasovagal Syncope.

Vasovagal syncope (VVS) refers to a heterogeneous group of conditions whereby the cardiovascular reflexes normally controlling the circulation are interrupted irregularly in response to a trigger, resulting in vasodilation, bradycardia, or both. VVS affects one-third of the population at least once in their lifetime or by the age of 60, reduces the quality of life, and may cause disability affecting certain routines. It poses a considerable economic burden on society, and, despite its prevalence, there is currently no proven pharmacological treatment for preventing VVS. The novel procedure of ganglionated plexus (GP) ablation has emerged rapidly in the past two decades, and has been proven successful in treating syncope. Several parameters influence the success rate of GP ablation, including specific ablation sites, localization and surgical techniques, method of access, and the integration of other interventions. This review aims to provide an overview of the existing literature on the physiological aspects and clinical effectiveness of GP ablation in the treatment of VVS. Specifically, we explore the association between GPs and VVS and examine the impact of GP ablation procedures as reported in human clinical trials. Our objective is to shed light on the therapeutic significance of GP ablation in eliminating VVS and restoring normal sinus rhythm, particularly among young adults affected by this condition.

Translation and Validation Study of the Hypoglycemia Fear Survey in a Greek Population of Children and Adolescents with Type 1 Diabetes Mellitus and their Parents.

The present study attempted to translate and culturally adapt an established research instrument, the Hypoglycemia Fear Survey (HFS) questionnaire, to the Greek population and evaluate its validity and internal consistency so that it can be used for the assessment of hypoglycemia fear in Greek children and adolescents with T1DM and their parents. One hundred Greek children and adolescents with T1DM, 54 males, 6-18 years old, and one of their parents participated in this validation study. The participants completed the translated Greek HFS, which includes one version for children (CHFS) and one for parents (PHFS). Exploratory Factor Analysis (EFA) was used to assess construct validity. Internal consistency was assessed using Cronbach's alpha, and convergent validity was established by estimating the correlation coefficients between the scores of the HFS scales/subscales and the different constructs of the Pediatric Quality of Life Inventory. The CHFS and PHFS exhibited adequate internal consistency for the total score and the Worry subscale, but lower consistency for the Behavior subscale. High test-retest reliability was also shown. We conclude that the Greek version of the HFS is a valid and reliable instrument to assess the fear of hypoglycemia in Greek children and adolescents with T1DM and their parents.

Evaluation of the treatment options for COVID-19 patients using generalized hesitant fuzzy- multi criteria decision making techniques.

The breakout of the pandemic COVID-19 has affected numerous countries and territories worldwide. As COVID-19 specific medicines yet to be invented, at present the treatment is case specific, hence identification and evaluation of different prevalent treatment options based on various criteria and attributes are very important not only from the point of view of present pandemic but also for futuristic pandemic preparedness. The present study focuses on identifying, evaluation and ranking of treatment options using Multi Criteria Decision Making (MCDM). In this regard, the existing literature, doctors and scientist were interviewed to know the current treatment options in vogue and the scale of their importance with respect to the criteria. The criteria taken are side effect, regime cost, treatment duration, plasma stability, plasma turnover, time of suppression, ease of application, drug-drug interaction, compliance, fever, pneumonia, intensive care, organ failure, macrophage activation syndrome, hemophagocytic syndrome, pregnancy, kidney problem, age. This study extended Hesitant Fuzzy Set (HFS) to Generalized Hesitant Fuzzy Sets (GHFS). Generalized Hesitant Pentagonal Fuzzy Number (GHPFN) is developed. The properties of GHPFN are demonstrated. Two types of GHPFN has been described. The GHPFN (2nd type) along with MCDM tool Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) has been applied to rank the treatment options. The result of the study ranked 'Hydroxychloroquine' as the first alternative followed by, 'Plasma Exchange', 'Tocilizumab', 'Remdesivir' and 'Favipravir'. To check the robustness and steadiness of the proposed methodology, comparative analysis and sensitivity analysis has been conducted.

Intraoperative endoscope view classification of neurovascular compression in hemifacial spasm condition: a single neurosurgeon prospective cross-sectional study.

Hemifacial spasm is a neurological disorder that causes involuntary contractions of facial muscles on one side of the face. This study aims to analyze the intraoperative pattern of neurovascular compression (NVC) and discuss relevant decompression techniques for 29 patients with hemifacial spasm who underwent endoscopy-assisted microvascular decompression (EAMVD). Patients and Methods: This was a prospective, single center, single neurosurgeon, cross-sectional study conducted from November 2020 to August 2022. All patients received EAMVD, and the NVC culprit vessel, compression site, severity, and type were analyzed using a 30-degree endoscope. Results: All 29 patients had successful interposition EAMVD without postoperative symptoms. The most common NVC site was REX (18 in 29 cases), the most common vessel to compress the seventh nerve was AICA (23 in 29 cases), while the most common type of NVC was loop (22 in 29 cases). NVC severity: 17 cases of mild compression, 4 cases of moderate compression, and 8 cases of severe compression. Without an angled telescope, we will miss the NVC in 12 cases (41.3%). Conclusion: EAMVD using an angled endoscope is a promising technique for treating hemifacial spasm. Intraoperative analysis of NVC can lead to a better understanding of the patterns of compression and may help in selecting appropriate decompression techniques.

Sensory gating functions of the auditory thalamus: Adaptation and modulations through noise-exposure and high-frequency stimulation in rats.

The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.

Capecitabine and Hand-foot Syndrome: A Case Report.

Capecitabine, a prodrug of 5-fluorouracil, is an FDA-approved drug for adjuvant treatment of colon, metastatic colorectal, and breast cancer. A variety of mucocutaneous adverse effects has been recognized with capecitabine. The pathogenesis of such manifestations still remains an enigma though various theories have been proposed. Here, we report two such cases. A 59-year-old female with carcinoma of the sigmoid colon on palliative therapy developed localized cutaneous hyperpigmentation of the palms and soles secondary to capecitabine in her 2nd cycle. Another case was of a 42-year-old female with stomach adenocarcinoma, who developed similar adverse effects after administration of capecitabine in her 4th cycle. Since these drugs have been widely used in recent years due to their relative ease in administration, the relative unawareness of Hand-foot syndrome (HFS) caused due to this drug makes it a prudent topic to be reported.

Hyaline Fibromatosis Syndrome Presenting with Nasal Mass: A Case Report.

Hyaline fibromatosis syndrome (HFS) is a rare, autosomally-recesfvsive disease characterized by papulonodular skin lesions, soft tissue masses, joint contractures, gingival overgrowth, and osteolytic bone lesions. Mutations in capillary morphogenesis gene 2 are responsible for both these conditions. Generally, an autosomal recessive pattern is assumed to be the most common mode of inheritance. Here, we report an unusual case of a twenty-three-year-old female patient with HFS who reported with a chief complaint of growing nasal mass for three months. There was no history of pain or bleeding associated with the nasal mass. Due to the growing mass, she experienced right nasal obstruction, which compromised her quality of life. There was an unremarkable family history. Her physical examination revealed multiple asymptomatic pinkish-white papulonodular lesions located at multiple sites. Intra orally, she had generalized gingival enlargement. Her nasal examination revealed a right sided nasal mass, bright red in color. The lesion was soft on palpation. All the results of hematological and biochemical tests were normal. However, skeletal radiographic examination showed the joint contractures on her knees and elbows without the presence of osteolytic bone lesions. The nasal lesion was surgically excised and histopathological examination revealed features suggestive of HFS.

Simultaneous microvascular decompression for trigeminal neuralgia and hemifacial spasm involving a dolichoectatic vertebral artery in an elderly patient: illustrative case.

BACKGROUND: Hyperactive cranial neuropathies refractory to medical management can often be debilitating to patients. While microvascular decompression (MVD) surgery can provide relief to such patients when an aberrant vessel is compressing the root entry zone (REZ) of the nerve, the arteries of elderly patients over 65 years of age can be less amenable to manipulation because of calcifications and other morphological changes. A dolichoectatic vertebral artery (DVA), in fact, can lead to multiple cranial neuropathies; therefore, a strategy for MVDs in elderly patients is useful. OBSERVATIONS: A 76-year-old man presented with medically refractory trigeminal neuralgia (TN) and hemifacial spasm (HFS). A DVA was the conflicting vessel at the left REZs of the trigeminal and facial nerves. The authors performed a retrosigmoid craniotomy for MVD of the DVA with Teflon padding at both REZs in approximately 1 hour of operative time. The patient was free of facial pain and spasm immediately after surgery and at follow-up. LESSONS: The authors described the case of an elderly patient with both TN and HFS caused by compression of a DVA. Simultaneous MVD with Teflon padding at both REZs provided symptomatic relief with limited surgical time. This can be a particularly useful and straightforward surgical strategy in the elderly population.

Self-assembled complete hair follicle organoids by coculture of neonatal mouse epidermal cells and dermal cells in Matrigel.

Background: 3D organoid cultures of hair follicles (HFs) are powerful models that mimic native HF for both in-depth study of HF disease and precision therapy. However, few studies have investigated the complete structure and properties of HF organoids. To investigate and characterize the complete HF organoids self-assembled by coculture of neonatal mouse epidermal cells (MECs) and dermal cells in Matrigel. Methods: Fresh epidermal and dermal cells from newborn mice (n=4) were isolated, and cocultured (1:1 ratio) in Matrigel using DMEM/F12 medium for 1 week. During the culture, an inverted microscope was used to observe the morphology of the 3D constructs. After 1 week, hematoxylin-eosin (HE) and immunofluorescence (IF) staining of HF-related markers (K5, K73, AE13, and K10), HF stem cell markers (K15, CD34, CD49f), skin-derived precursor-related marker (Nestin), and dermal papillae (DP)-specific markers (SOX2 and ALP) was performed in the harvested constructs to identify the HF organoids. Results: Epidermal and dermal cells self-assembled into HF organoids comprising an infundibular cyst-like structure, a lower segment-like structure, and a bulb-like structure from tail to root. The HF organoid had multiple, well-defined compartments similar to native anagen HF. Of the three segments, K73 was expressed in the inner root sheath-like layer, AE13 was localized in the hair shaft-like structure, K5, K15, CD34, and CD49f were present in the outer root sheath-like layer, Nestin labeled the connective tissue sheath-like layer, and SOX2 and ALP were expressed in the DP-like structure. Furthermore, K10 and K73 were expressed in the infundibular cyst-like structure. The expression of these molecular proteins was consistent with native anagen HF. Conclusions: The complete HF organoid regenerated in Matrigel has specific compartments and is an excellent model to study HF disease and precision therapy.

Laser Irradiation Effect on the p-GaSe/n-HfS2 PN-Heterojunction for High-Performance Phototransistors.

Two-dimensional (2D)-based PN-heterojunction revealed a promising future of atomically thin optoelectronics with diverse functionalities in different environments. Herein, we reported a p-GaSe/n-HfS2 van der Waals (vdW) heterostructure for high-performance photodetectors and investigated the laser irradiation effect on the fabricated device. The fabricated 2D vdW heterostructure revealed a high photoresponsivity of 1 × 104 A W-1 with a photocurrent value of 377 nA due to unique type-II band alignment and enhanced surface potential under light illumination, which is further confirmed by density functional theory (DFT) calculations. Before laser irradiation, the device showed high field-effect mobility (µEF) of 26.37 cm2 V-1 s-1, ON/OFF ratio of ∼105, and threshold voltage swing (SS) of ∼463 mV dec-1. With the exposure of 690 mW cm-2 laser power density, µEF reached 204 cm2 V-1 s-1, although ∼2 V ΔVth shifts are observed along with the SS decreased to 175 mV dec-1. Interestingly, the reduced SS shows better channel control of the fabricated device with laser power. Similarly, the ON/OFF ratio decreased to ∼1.29 × 103. The results indicate that the creation of oxide trap charges at the interface of SiO2 and PN-heterojunction layers was observed with voltage biasing and high laser power density. The degradation of electrical parameters is attributed to fewer interface trap charges per surface area of the device rather than direct damage in PN-heterojunction layers. Considering the excellent 2D electronic properties, these materials are better candidates for future high-radiation environments.

Retrieval and Ranking of Combining Ontology and Content Attributes for Scientific Document.

Traditional mathematical search models retrieve scientific documents only by mathematical expressions and their contexts and do not consider the ontological attributes of scientific documents, which result in gaps between the queries and the retrieval results. To solve this problem, a retrieval and ranking model is constructed that synthesizes the information of mathematical expressions with related texts, and the ontology attributes of scientific documents are extracted to further sort the retrieval results. First, the hesitant fuzzy set of mathematical expressions is constructed by using the characteristics of the hesitant fuzzy set to address the multi-attribute problem of mathematical expression matching; then, the similarity of the mathematical expression context sentence is calculated by using the BiLSTM two-way coding feature, and the retrieval result is obtained by synthesizing the similarity between the mathematical expression and the sentence; finally, considering the ontological attributes of scientific documents, the retrieval results are ranked to obtain the final search results. The MAP_10 value of the mathematical expression retrieval results on the Ntcir-Mathir-Wikipedia-Corpus dataset is 0.815, and the average value of the NDCG@10 of the scientific document ranking results is 0.9; these results prove the effectiveness of the scientific document retrieval and ranking method.

Intermediate nerve neuralgia developed during hemifacial spasm follow-up: illustrative case.

BACKGROUND: Intermediate nerve neuralgia (INN) is a rare condition believed to be caused by vascular compression, with external auditory canal pain as the chief symptom. The authors reported a rare case of a 78-year-old woman who developed INN during follow-up for hemifacial spasm (HFS). OBSERVATIONS: The patient had been receiving Botox treatment for right HFS for 20 years when she developed paroxysmal electric shock pain in the right external auditory canal and tinnitus induced by opening her mouth. A three-dimensional magnetic resonance fusion image showed the cisternal portion of the facial-vestibulocochlear nerve complex to be compressed by the meatal loop of the anterior inferior cerebellar artery (AICA), which was pressed against by the posterior inferior cerebellar artery. The authors diagnosed INN, and microvascular decompression (MVD) was performed. Surgical findings were consistent with preoperative neuroimaging. In addition, the proximal portion of the meatal loop of the AICA had passed between the facial and vestibulocochlear nerves, compressing both. The AICA was moved and the nerve completely decompressed. All symptoms improved immediately following surgery. LESSONS: When INN occurs during HFS follow-up, aggressive MVD should be considered based on detailed neuroimaging. This treatment is a very effective single-stage cure for INN, HFS, and vestibulocochlear symptoms.

A First-Principles Study on the Electronic, Thermodynamic and Dielectric Properties of Monolayer Ca(OH)2 and Mg(OH)2.

We perform first-principles calculations to explore the electronic, thermodynamic and dielectric properties of two-dimensional (2D) layered, alkaline-earth hydroxides Ca(OH)2 and Mg(OH)2. We calculate the lattice parameters, exfoliation energies and phonon spectra of monolayers and also investigate the thermal properties of these monolayers, such as the Helmholtz free energy, heat capacity at constant volume and entropy as a function of temperature. We employ Density Functional Perturbation Theory (DFPT) to calculate the in-plane and out-of-plane static dielectric constant of the bulk and monolayer samples. We compute the bandgap and electron affinity values using the HSE06 functional and estimate the leakage current density of transistors with monolayer Ca(OH)2 and Mg(OH)2 as dielectrics when combined with HfS2 and WS2, respectively. Our results show that bilayer Mg(OH)2 (EOT∼0.60 nm) with a lower solubility in water offers higher out-of-plane dielectric constants and lower leakage currents than does bilayer Ca(OH)2 (EOT∼0.56 nm). Additionally, the out-of-plane dielectric constant, leakage current and EOT of Mg(OH)2 outperform bilayer h-BN. We verify the applicability of Anderson's rule and conclude that bilayers of Ca(OH)2 and Mg(OH)2, respectively, paired with lattice-matched monolayer HfS2 and WS2, are effective structural combinations that could lead to the development of innovative multi-functional Field Effect Transistors (FETs).

Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression.

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 3'UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

A retrieval and ranking method of mathematical documents based on CA-YOLOv5 and HFS.

In a retrieval system for mathematical documents based on mathematical expressions, the input and matching of mathematical expressions are key steps that affect the system's usability, accessibility and efficiency because of their special attributes. Therefore, this paper mainly focuses on improving the input efficiency and matching accuracy of mathematical expressions. This paper proposes a method for retrieval and ranking of mathematical documents based on CA-YOLOv5 and HFS (hesitation fuzzy set) by utilizing the advantages of CA (coordinate attention) model and YOLOv5 in target detection and the superiority of HFS in multiattribute decision-making. By embedding the CA model into the YOLOv5 network, the mathematical expressions in layout images are extracted and recognized to form mathematical query expressions. These expressions are then analyzed to obtain similarity evaluation features and matched with the candidate mathematical expressions indexed with the same features in a library of mathematical documents by employing the HFS as the similarity evaluation measure. Experiments were performed based on the TFD-ICDAR2019v2 dataset and the NTCIR dataset. The F1-score of the mathematical expression detection result was 76.54%, the MAP (mean average precision) of the mathematical documents retrieval result was 71.73%, and the average nDCG of mathematical documents ranking was 80.89%.

First-Principles Calculations of Two-Dimensional CdO/HfS2 Van der Waals Heterostructure: Direct Z-Scheme Photocatalytic Water Splitting.

Using two-dimensional (2D) heterostructure as photocatalyst for water splitting is a popular strategy for the generation of hydrogen. In this investigation, the first-principles calculations are explored to address the electronic performances of the 2D CdO/HfS2 heterostructure formed by van der Waals (vdW) forces. The CdO/HfS2 vdW heterostructure has a 1.19 eV indirect bandgap with type-II band alignment. Importantly, the CdO/HfS2 vdW heterostructure possesses an intrinsic Z-scheme photocatalytic characteristic for water splitting by obtaining decent band edge positions. CdO donates 0.017 electrons to the HfS2 layer in the heterostructure, inducing a potential drop to further separate the photogenerated electrons and holes across the interface. The CdO/HfS2 vdW heterostructure also has excellent optical absorption capacity, showing a promising role as a photocatalyst to decompose the water.