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The incidence of cancer of unknown primary site with metastases to neck lymph nodes is low, according to literature it varies between 2% and 9%, and is further declining due to more precise diagnostics. Histologically, squamous cell carcinomas are most common. In addition to general physical examination with special focus on the head and neck region, endoscopic examination with visualization of nasopharynx, oropharynx, larynx and hypopharynx, and radiological imaging (CT and/or MRI, and in case of indication PET/CT) is necessary. Surgical treatment is the oldest but still very important method of treating these patients and is the preferred option for initial treatment. On the other hand, primary radiotherapyis an important treatment option for head and neck tumors, especially in patients who are not candidates for surgical treatment, and it is recommended to combine it with chemotherapy in patients with advanced disease (N2-3). After initial surgical treatment and pathohistological findings of N2 or N3 disease, radiotherapy with or without chemotherapy is indicated in all patients, and may also be considered in those with N1 status. For both primary and adjuvant radiotherapy the volume of radiation fields remains a controversial topic. Treatment options range from surgical treatment of the ipsilateral side of the neck without adjuvant treatment, surgical treatment with adjuvant (chemo)radiotherapy, to primary treatment – irradiation of both sides of the neck with all the sites from which the primary tumor could originate. Earlier, the guidelines advocated a more aggressive approach that included radiotherapy of the entire volume of the pharynx (nasopharynx, oropharynx, and hypopharynx) and larynx and both sides of the neck. Over time, there has been a noticeable shift towards more conservative treatment, most often in terms of surgical treatment of neck metastases with the use of adjuvant ipsilateral radiotherapy, without irradiating all pharyngeal and laryngeal mucosa. The most important parameters in the decision regarding concomitant chemotherapy are lymph node capsule perforation and R1 / 2 resection.

Inglese et al. develop a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted magnetic resonance imaging scans. Their model reliably discriminates people with Alzheimer’s disease-related pathologies from those without.

Gorham–Stout disease (GSD) is a rare bone disease characterized by massive osteolysis and lymphatic proliferation. The origin of the condition is unknown, and no established treatment protocol exists. Massive pleural effusion is a frequent complication of GSD in the thoracic region. We present the case of a 23-year-old male with thoracic GSD, subsequent paraparesis, and life-threatening pleural effusion. The patient was managed by a multidisciplinary team with a good recovery. The pleural effusion was successfully treated with a pleuro-peritoneal shunt. This is the first report of the use of this mini-invasive technique in the management of pleural effusion related to GSD. Further, we present the potential role of interleukin-6 and bone resorption markers in the measurement of the disease activity.

This study aimed to examine the effect of corporate governance and capital structure on the performance of family and non-family firms. Corporate governance is measured by independent boards of directors and commissioners. Capital structure was measured by debt-to-equity ratio and performance as proxied by return on equity. The data in this research was secondary data. The sampling method used the purposive sampling method. The samples were 11 family firms and 30 non-family firms. The data analysis used multiple regression to identify the effect of the dependent variable on the independent variable. The results of the research showed that the capital structure has a significant impact on the performance of family and non-family firms.

Modern society presents a problem where it is increasingly common for minority groups/cultural groups/indigenous groups to show their identity to fulfill their collective right to vote in politics. This study aims to describe the form of democracy that is still hampered because the fulfillment of the voting rights of the Mandailing community is still limited. This research is qualitative descriptive research conducted in the Mandailing community in Kecamataan Sungai Kanan. Data was collected through interviews, observation, and documentation. The collected data is then analyzed using Creswell's techniques which consist of organizing and preparing the data, reading the data, the coding process or general analysis, the coding categorization process that has been made, and describing the themes into qualitative explanations and analysis. The results of this study prove that the level of understanding of the Mandailing community on the importance of the right to vote is still shallow; this is related because the KPU, as the organizer, does not seriously socialize the political rights of citizens. In this case, the right to vote and be elected. Meanwhile, monotonous activities are always represented by the Mandailing community by representing their voting rights to traditional leaders or elders in the area.

The aetiology of the TDP-43 aggregation manifest itself in the muscle and neuronal cells. Here authors show cell-type characteristic functions of TDP43, reflected in aberrant splicing, likely contributing to disease development.

Recently, village-based tourism has been discussed by practitioners and academics after considering the importance of the criteria before destination development. However, there are limited studies concerning these criteria, specifically village-based tourism. Therefore, this study aims to develop the village-based tourism criteria. The literature review showed that thirteen criteria are being suggested, and the experts from the government agency and academics from the tourism department were surveyed using questioners. The twenty-seven experts who participated in this study were analyzed using nonparametric statistics, such as the Mann Whitney and Kruskal Wallis tests, to gain agreement among samples. Therefore, the exploratory factor analysis was conducted to classify the criteria into several factors, also this study was developed using the measurement model. The result showed two types of village-based tourism criteria: (ii) Attractive condition, and parking factor, and (ii) Appealing activity, essential condition, and mitigation factor. Practically, this finding can be considered while developing the village-based tourism criteria and literature.

This paper is the result of the collective work undertaken by a group of Psychological Contract (PC) and Sustainability scholars from around the world, following the 2023 Bi-Annual PC Small Group Conference (Kedge Business School, Bordeaux, France). As part of the conference, scholars engaged in a workshop designed to generate expert guidance on how to aid the PC field to be better aligned with the needs of practice, and thus, impact the creation and maintenance of high-quality and sustainable exchange processes at work. In accordance with accreditation bodies for higher education, research impact is not limited to academic papers alone but also includes practitioners, policymakers, and students in its scope. This paper therefore incorporates elements from an impact measurement tool for higher education in management so as to explore how PC scholars can bolster the beneficial influence of PC knowledge on employment relationships through different stakeholders and means. Accordingly, our proposals for the pursuit of PC impact are organized in three parts: (1) research, (2) practice and society, and (3) students. Further, this paper contributes to the emerging debate on sustainable PCs by developing a construct definition and integrating PCs with an 'ethics of care' perspective. [ABSTRACT FROM AUTHOR]

Insulin secretion increases progressively during pregnancy to maintain normal maternal blood glucose levels. The placenta plays a crucial role in this process by releasing hormones and extracellular vesicles into the maternal circulation, which drive significant changes in pregnancy physiology. Placental extracellular vesicles, which are detectable in the plasma of pregnant women, have been shown to signal peripheral tissues and contribute to pregnancy-related conditions. While studies using murine models have demonstrated that extracellular vesicles can modulate insulin secretion in pancreatic islets, it remains unclear whether these effects translate to human biology. Understanding how placental signals enhance insulin synthesis and secretion from β cells could be pivotal in developing new therapies for diabetes. In our study, we isolated placental small extracellular vesicles from human placentae and utilised the human β cell line, EndoC-βH3, to investigate their effects on β-cell function in vitro. Our results indicate that human β cells internalise placental small extracellular vesicles, leading to enhanced insulin gene expression and increased insulin content within the β cells. Moreover, these vesicles up-regulated the expression of Annexin A1, a protein known to increase insulin content. This up-regulation of Annexin A1 holds promise as a potential mechanism by which placental small extracellular vesicles enhance insulin biosynthesis. [ABSTRACT FROM AUTHOR]

Background: Pro- and anti-inflammatory cytokines help regulate the inflammatory response. A cytokine storm is a dysregulated cytokine response associated with sepsis and other conditions that result in a hyper-inflammatory state. Extracorporeal cytokine adsorption has the potential to restore a balanced inflammatory response. Hemoperfusion with CytoSorb® (CS) appears to be a short-term mode of treatment of sepsis in both adults and children. Objective: We present a case series of eight critically ill children involving the use of hemoperfusion with CS at the University Medical Center Ljubljana to treat clinically manifested cytokine storm. Results: In our preliminary experience, it was applied without complication in five children weighing more than 10 kg, who all survived. The effect of age on complications regarding CS treatment is unclear, yet in our case series, all three patients weighing less than 10 kg died of their disease. Conclusions: In our preliminary experience, cytokine adsorption with CS remains a potential adjunctive treatment for cytokine storm in critically ill children. [ABSTRACT FROM AUTHOR]

Hand-Eye Coordination (HEC) and Hand Grip Strength (HGS) are among the most important skills in Taekwondo. On a technical level, HEC reflects neuromuscular coordination ability which enables quick responses, and HGS reflects muscle strength which indicates the strength and overall health of the athletes. Combined together, HEC and HGS likely allow Taekwondo athletes to perform better. The aim of this study was to identify if there is a relationship between HEC and HGS in elite Taekwondo athletes. 166 elite Taekwondo athletes (141 males, 25 females) voluntarily participated in this study and were divided into two categories: seniors (age >17 years) and juniors (age =17 years). HEC was assessed by hand-eye coordination manual dexterity test (Lafayette, IN, US) and HGS was measured using a hand dynamometer (Takei, Niigata, Japan). The results revealed that no significant relationship was observed between HEC and HGS (p>0.05) in elite Taekwondo athletes. Despite the several strength and neuromuscular adaptations acquired during Taekwondo practice, HEC and HGS are not significantly correlated, and hence there is no relationship between HEC and HGS in elite Taekwondo athletes. The results obtained may benefit Taekwondo coaches and athletes in improving their training strategies. [ABSTRACT FROM AUTHOR]

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12–16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Tribally employed, Community Health Representatives (CHRs) serving Indigenous and American Indian and Alaskan Native (AIAN) peoples are culturally and linguistically embedded community leaders, with the unique ability to serve as the link and intermediary between community members and systems. Unique to the CHR workforce scope of practice is the expectation for high level integration within the medical and social service care team. This explicit role outlined in the scope of work sets an expectation for both CHR and care teams to deliver integrated patient, family, and systems level care coordination and case management. This paper aims to build from our previous manuscript published in Volume 1 of the special issue Community Health Workers Practice from Recruitment to Integration. In that Volume, we explored through a Community Case Study CHR Managers' perspectives on the challenges and opportunities for full CHR integration into health systems and teams serving AIAN. In this paper, we offer new information about the current CHR and CHR Managers' involvements and perceived level of integration within health care teams and the broader public health systems addressing the social and structural determinants of health. We approach this topic considering the COVID-19 pandemic and how CHRs and CHR Programs were included and not included in tribal pandemic response efforts.

Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably (>95% accuracy) detect SARS-CoV-2 at a concentration of 84 genome equivalents per milliliter (GE/mL). The vast majority of diagnostic methods meeting our analytical criteria that are currently authorized for use by the United States Food and Drug Administration with the Coronavirus Disease 2019 (COVID-19) Emergency Use Authorization require higher concentrations of the virus to achieve this degree of sensitivity and specificity. In addition, we can reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy given sufficient viral load. The genotypic data in these genome assemblies enable the more effective analysis of disease spread than is possible with an ordinary binary diagnostic. These data can also help identify vaccine and drug targets. Finally, we show that the diagnoses obtained using POLAR of positive and negative clinical nasal mid-turbinate swab samples 100% match those obtained in a clinical diagnostic lab using the Center for Disease Control's 2019-Novel Coronavirus test. Using POLAR, a single person can manually process 192 samples over an 8-hour experiment at the cost of ~$36 per patient (as of December 7th, 2022), enabling a 24-hour turnaround with sequencing and data analysis time. We anticipate that further testing and refinement will allow greater sensitivity using this approach.

INTRODUZIONE: Gli infermieri utilizzano il ragionamento clinico per guidare le azioni da porre in essere al fine di garantire alla persona un’assistenza adeguata. Il ragionamento clinico richiede tempo per instaurarsi nell’operato di un professionista sanitario e per tale ragione è necessario che questa competenza venga acquisita sin dall’inizio del percorso di formazione di base. Sono esigue le indagini che valutano il grado di acquisizione delle abilità di ragionamento clinico degli studenti infermieri. OBIETTIVI: Obiettivo primario è stato quello di valutare la capacità di ragionamento clinico degli studenti infermieri. Obiettivo secondario è stato analizzare i fattori correlati alle capacità di ragionamento clinico. METODI: La raccolta dati ha previsto la somministrazione della versione italiana dello strumento Nurse Clinical Reasoning Scale. Il Test di Pearson e il Test Anova sono stati utilizzati per esplorare i fattori connessi al ragionamento clinico. RISULTATI: 205 studenti hanno risposto al questionario. Gli studenti hanno dichiarato difficoltà nel porre in essere alcune abilità utili allo sviluppo del ragionamento clinico. L’anno di corso (p

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression.

Programmed ribosomal frameshifting (PRF) occurs in many viruses including SARS-CoV-2 to allow the translation of multiple proteins from a single transcript. Here, the authors identify the human short isoform of the zinc-finger antiviral protein (ZAP-S) as a direct regulator of PRF in SARS-CoV-2 that severely impairs SARS-CoV-2 frameshifting in cells and directly interacts with the SARS-CoV-2 RNA; interfering with the folding of the frameshift RNA element.

Many RNA viruses employ programmed –1 ribosomal frameshifting (PRF) to expand their coding capacity and optimize production of viral proteins. Here, the authors report structural and biophysical analysis of protein 2A from a cardiovirus, with insights into the mechanism of its PRF-stimulatory function.

Uvod: O kronični pooperativni bolečini govorimo, kadar ne najdemo drugega vzroka za njen nastanek in ko traja dlje kot 2 meseca po operaciji. Pojavi se pri 10-50 % bolnikov po velikih abdominalnih operacijah. Podskupina kronične bolečine, ki jo je najtežje zdraviti, je kronična nevropatska bolečina. Medoperativna epiduralna analgezija in infuzija deksmedetomidina lahko vplivata na incidenco kronične pooperativne bolečine in na incidenco nevropatske bolečine. Metode: V prospektivno raziskavo smo vključili odrasle kirurške bolnike, sprejete na KO za abdominalno kirurgijo, pri katerih je bila načrtovana operacija želodca, operacija trebušne slinavke ali operacija črevesja. Vsi bolniki so imeli epiduralno analgezijo in medoperativno infuzijo deksmedetomidina. Tri mesece po operaciji smo bolnikom poslali vprašalnike. Ocenjevali smo jakost in vrsto bolečine. Za oceno smo uporabili DN4 (Douleur Neuropathique 4) in vprašalnik painDetect. Rezultati: Prejeli smo 42 (50 %) pravilno izpolnjenih vprašalnikov DN4 in 45 (53 %) vprašalnikov painDetect. V naši raziskavi je bila incidenca kronične bolečine 25 %, nevropatske bolečine 7,1 % (3 bolniki so izpolnjevali merila za nevropatsko bolečino po vprašalniku DN4). Zaključek: Rezultati naše prospektivne raziskave nakazujejo, da bi lahko medoperativna uporaba epiduralne analgezije in infuzije deksmedetomidina zmanjšala pojav pooperativne kronične bolečine.

Background and purpose — Lumbar disc herniation is a common surgically treated condition in the working-age population. We assessed health-related risk factors for return to work (RTW) after excision of lumbar disc herniation. Previous studies on the subject have had partly contradictory findings. Patients and methods — RTW of 389 (n = 111 male, n = 278 female; mean age 46 years, SD 8.9) employees who underwent excision of lumbar disc herniation was assessed based on the Finnish Public Sector Study (FPS). Baseline information on occupation, preceding health, and health-risk behaviors was derived from linkage to national health registers and FPS surveys before the operation. The likelihood of RTW was analyzed using Cox proportional hazard univariable and multivariable modelling. Results — 95% of the patients had returned to work at 12 months after surgery, after on average 78 days of sickness absence. Faster RTW in the univariable Cox model was associated with a small number of sick leave days (< 30 days) before operation (HR 1.3, 95% CI 1.1–1.6); high occupational position (HR 1.6, CI 1.2–2.1); and age under 40 years (HR 1.5, CI 1.1–1.9). RTW was not associated with sex or the health-related risk factors obesity, physical inactivity, smoking, heavy alcohol consumption, poor self-rated health, psychological distress, comorbid conditions, or purchases of pain or antidepressant medications in either the univariable or multivariable model. Interpretation — Almost all employees returned to work after excision of lumbar disc herniation. Older age, manual job, and prolonged sick leave before the excision of lumbar disc herniation were risk factors for delayed return to work after the surgery.

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Longitudinal studies provide the unique opportunity to test whether early language provides a scaffolding for the acquisition of the ability to read. This study tests the hypothesis that parental language input during the first 2 years of life predicts emergent literacy skills at 5 years of age, and that white matter development observed early in the 3rd year (at 26 months) may help to account for these effects. We collected naturalistic recordings of parent and child language at 6, 10, 14, 18, and 24 months using the Language ENvironment Analysis system (LENA) in a group of typically developing infants. We then examined the relationship between language measures during infancy and follow-up measures of reading related skills at age 5 years, in the same group of participants (N = 53). A subset of these children also completed diffusion and quantitative MRI scans at age 2 years (N = 20). Within this subgroup, diffusion tractography was used to identify white matter pathways that are considered critical to language and reading development, namely, the arcuate fasciculus (AF), superior and inferior longitudinal fasciculi, and inferior occipital-frontal fasciculus. Quantitative macromolecular proton fraction (MPF) mapping was used to characterize myelin density within these separately defined regions of interest. The longitudinal data were then used to test correlations between early language input and output, white matter measures at age 2 years, and pre-literacy skills at age 5 years. Parental language input, child speech output, and parent-child conversational turns correlated with pre-literacy skills, as well as myelin density estimates within the left arcuate and superior longitudinal fasciculus. Mediation analyses indicated that the left AF accounted for longitudinal relationships between infant home language measures and 5-year letter identification and letter-sound knowledge, suggesting that the left AF myelination at 2 years may serve as a mechanism by which early language experience supports emergent literacy.

Between 6 and 12 months of age there are dramatic changes in infants’ processing of language. The neurostructural underpinnings of these changes are virtually unknown. The objectives of this study were to (1) examine changes in brain myelination during this developmental period and (2) examine the relationship between myelination during this period and later language development. Macromolecular proton fraction (MPF) was used as a marker of myelination. Whole-brain MPF maps were obtained with 1.25 mm3 isotropic spatial resolution from typically developing children at 7 and 11 months of age. Effective myelin density was calculated from MPF based on a linear relationship known from the literature. Voxel-based analyses were used to identify longitudinal changes in myelin density and to calculate correlations between myelin density at these ages and later language development. Increases in myelin density were more predominant in white matter than in gray matter. A strong predictive relationship was found between myelin density at 7 months of age, language production at 24 and 30 months of age, and rate of language growth. No relationships were found between myelin density at 11 months, or change in myelin density between 7 and 11 months of age, and later language measures. Our findings suggest that critical changes in brain structure may precede periods of pronounced change in early language skills.