Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of a Paradigm Switch in Diagnosis and Treatment of HPV-Driven Head and Neck Cancer—Striking the Balance Between Toxicity and Cure

More than a decade after the discovery of p16 immunohistochemistry (IHC) as a surrogate for human papilloma virus (HPV)-driven head and neck squamous cell carcinoma (HNSCC), p16-IHC has become a routinely evaluated biomarker to stratify oropharyngeal squamous cell carcinoma (OPSCC) into a molecularly distinct subtype with favorable clinical prognosis. Clinical trials of treatment de-escalation frequently use combinations of biomarkers (p16-IHC, HPV-RNA in situ hybridization, and amplification of HPV-DNA by PCR) to further improve molecular stratification. Implementation of these methods into clinical routine may be limited in the case of RNA by the low RNA quality of formalin-fixed paraffin-embedded tissue blocks (FFPE) or in the case of DNA by cross contamination with HPV-DNA and false PCR amplification errors. Advanced technological developments such as investigation of tumor mutational landscape (NGS), liquid-biopsies (LBx and cell-free cfDNA), and other blood-based HPV immunity surrogates (antibodies in serum) may provide novel venues to further improve diagnostic uncertainties. Moreover, the value of HPV/p16-IHC outside the oropharynx in HNSCC patients needs to be clarified. With regards to therapy, postoperative (adjuvant) or definitive (primary) radiochemotherapy constitutes cornerstones for curative treatment of HNSCC. Side effects of chemotherapy such as bone-marrow suppression could lead to radiotherapy interruption and may compromise the therapy outcome. Therefore, reduction of chemotherapy or its replacement with targeted anticancer agents holds the promise to further optimize the toxicity profile of systemic treatment. Modern radiotherapy gradually adapts the dose. Higher doses are administered to the visible tumor bulk and positive lymph nodes, while a lower dose is prescribed to locoregional volumes empirically suspected to be invaded by tumor cells. Further attempts for radiotherapy de-escalation may improve acute toxicities, for example, the rates for dysphagia and feeding tube requirement, or ameliorate late toxicities like tissue scars (fibrosis) or dry mouth. The main objective of current de-intensification trials is therefore to reduce acute and/or late treatment-associated toxicity while preserving the favorable clinical outcomes. Deep molecular characterization of HPV-driven HNSCC and radiotherapy interactions with the tumor immune microenvironment may be instructive for the development of next-generation de-escalation strategies.
Screening and Identification of Survival-Associated Splicing Factors in Lung Squamous Cell Carcinoma

Lung squamous cell carcinoma (LUSC) is a disease with high morbidity and mortality. Many studies have shown that aberrant alternative splicing (AS) can lead to tumorigenesis, and splicing factors (SFs) serve as an important function during AS. In this research, we propose an analysis method based on synergy to screen key factors that regulate the initiation and progression of LUSC. We first screened alternative splicing events (ASEs) associated with survival in LUSC patients by bivariate Cox regression analysis. Then an association network consisting of OS-ASEs, SFs, and their targeting relationship was constructed to identify key SFs. Finally, 10 key SFs were selected in terms of degree centrality. The validation on TCGA and cross-platform GEO datasets showed that some SFs were significantly differentially expressed in cancer and paracancer tissues, and some of them were associated with prognosis, indicating that our method is valid and accurate. It is expected that our method would be applied to a wide range of research fields and provide new insights in the future.
Increased Pain Symptomatology Among Females vs. Males With Fragile X-Associated Tremor/Ataxia Syndrome

Individuals with the fragile X premutation report symptoms of chronic pain from multiple systems, have increased incidence of comorbid conditions where pain is a prominent feature, and pathophysiology that supports disrupted pain regulation, inflammation, and energy imbalance. Less is known about how pain manifests for the subpopulation of carriers that develop the motor and cognitive changes of fragile X-associated tremor and ataxia syndrome (FXTAS), and how pain may differ between men and women. We gathered data collected from 104 males and females with FXTAS related to chronic pain, comorbid conditions related to pain, and medications used for pain control to further explore the types of pain experienced and to better characterize how individuals with the fragile X premutation experience pain sensation across genders. We found that women experience significantly more pain symptoms than men, particularly allodynia (20 vs. 2.0%, p = 0.008), peripheral neuropathy pain (43.9 vs. 25.4%, p = 0.0488), migraine (43.9 vs. 14.5%, p = 0.0008), fibromyalgia (26.8 vs. 0%, p = 0.0071) and back pain (48.5 vs. 23.4%, p = 0.008). We found onset of peripheral neuropathy predicts the onset of ataxia (β = 0.63 ± 0.25, p = 0.019) and tremor (β = 0.56 ± 0.17, p = 0.004) across gender. Women also report significantly more anxiety (82.9 vs. 39.7%, p < 0.001), which has implications for ideal pain treatment. These pain symptoms need to be recognized in the medical history and treated appropriately, with consideration for overlapping comorbidities.
Design of miniaturized single band‐notch micro strip antenna with enhanced UWB performance

In the present paper, design of a novel miniaturized single band‐notch microstrip antenna with enhanced ultra wide band performance is presented. To enhance bandwidth, rectangular shape radiator patch and modified ground plane are fed with a tapered microstrip feed line. The proposed antenna posses extended ultra wide bandwidth of 20.5 GHz (from 5.0 ‐ 25.5 GHz). Further, a L‐shaped slot is etched in the radiator to restrict electromagnetic interference at WLAN band. The antenna shows a 8 dB less gain in the stop‐band, while the gain at frequencies other than the stop band remains unchanged. The band‐notch antenna posses a bandwidth of 20.9 GHz (from 4.6‐ 25.5 GHz). The proposed antennas provide a wide usable fractional bandwidth of more than 134% with simple and ultra compact sizes of 11 × 16× 0.8 mm3. Time‐domain analysis of the proposed UWB antenna shows that it has good pulse handling capability along with stable group delay. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:1494–1499, 2016
The impact of the customer order decoupling point on type and level of supply chain integration

Literature suggests that more supply chain (SC) integration increases of SC performance. However, recent research shows that contextual factors affect the effectiveness of SC integration efforts. Specifically, the location of the customer order decoupling point (CODP) might be such a factor, but there is limited empirical evidence. This study explores the impact of the location of the CODP on SC integration. It empirically investigates upstream, internal and downstream SC integration efforts in twelve metal parts producing Dutch companies to offer a comprehensive view of the effects of the location of the CODP on SC integration. Our results show a clear relationship between SC integration and the location of the CODP. Specifically, make-to-order (MTO), assemble-to-order (ATO) and make-to-stock (MTS) companies show relatively high levels in upstream, internal and downstream SC integration, respectively. Moreover, MTO companies mainly share forecast information and engage in joint R&D with their suppliers, ATO companies focus on internal SC integration using information systems and planning, while MTS companies interact with their customers intensively to exchange forecast information. Our study adds to the insight on the application of SC integration in different situations and offers initial evidence for the effects of the location of the CODP on SC integration.
Changes in Mid-Depth Water Mass Ventilation in the Japan Sea Deduced From Long-Term Spatiotemporal Variations of Warming Trends

The influence of global warming on mid-depth water mass ventilation in the Japan Sea was investigated using both Argo-based and ship-based hydrographic datasets. The Argo-based dataset of the entire Japan Sea area revealed a warming trend during the past two decades in the upper portion of the Japan Sea Proper Water (UJSPW), which lies at intermediate depths from just under the main thermocline to approximately 1000 m. The warming rates in the southern Japan Sea are generally greater than those in the northern sea by a factor of 2–3. Long-term hydrographic data obtained over the last five decades in the northeast and southeast of the sea revealed that higher warming rates in the southern sea began from 2008, although a significant warming in both northern and southern seas was initiated from the late 1980s. A stagnation in the UJSPW formation from the late 1980s was suggested by a positive shift in the winter sea surface temperature in its formation region and a decreasing trend in dissolved oxygen concentration during the 1990s. In addition, a vertical multi-box model demonstrated that an imbalance between the heating from the upper layer and the cold water supply from its source region induces a warming in the UJSPW. We conclude that a significant change in the mid-depth water mass ventilation occurred in the entire Japan Sea in the late 1980s due to a stagnation in the UJSPW formation. Subsequently, a modest event in the mid-depth water mass ventilation have occurred since 2008. The higher warming rates in the southern sea than those in the northern sea in the event suggest a reduction in cold UJSPW supply to the southern sea from its formation region.
Outcomes of Liver Resection for Metabolic Dysfunction-Associated Fatty Liver Disease or Chronic Hepatitis B-Related HCC

Aims This study aims to determine differences in severity of background liver disease at hepatocellular carcinoma (HCC) diagnosis and long-term survival outcomes among patients undergoing liver resection for HCC in the background of metabolic dysfunction-associated fatty liver disease (MAFLD) compared to chronic hepatitis B (CHB) alone or concurrent CHB (CHB/MAFLD). Methods Patient demographics and comorbidities, clinicopathologic data, perioperative and long-term outcomes among patients who underwent liver resection for HCC were reviewed. Overall and recurrence-free survival were calculated with the Kaplan-Meier method, with the values compared using the log-rank test. Results From January 2014 to December 2018, 1325 patients underwent potential curative liver resection of HCC; 67 (5.0%), 176 (13.3%), and 1082 (81.7%) patients had MAFLD alone, CHB concurrent with MAFLD, and CHB alone, respectively. At HCC diagnosis, fewer MAFLD patients had cirrhosis, alpha fetoprotein concentration ≥ 400 ng/mL, tumor size ≥ 5 cm, mulinodular, microvascular invasion, receiving major hepatectomy, and receiving adjuvant transarterial chemoembolization. After a median follow-up of 47 months after liver resection, MAFLD (or MAFLD plus CHB/MAFLD) patients had significantly higher overall and recurrence-free survival than CHB patients before or after propensity score analysis (all P<0.05). Conclusion Patients with HCC in the setting of MAFLD have less-severe background liver disease at HCC diagnosis and better long-term survival after curative liver resection compared to counterparts with CHB/MAFLD or CHB.
Well-Being, PTSD, College Adjustment in Student Veterans With and Without Disabilities

We examined mediating effects of the pillars of well-being (i.e., positive emotion, engagement, relationships, meaning, and accomplishment) on the relationship between PTSD symptoms and college life adjustment for student veterans. We recruited 205 student veterans. Mediation analysis was conducted to test whether the pillars of well-being mediate the relationship between PTSD and college life adjustment. The results showed that positive emotion and accomplishment had mediating effects on the relationship between PTSD symptoms and college adjustment.
The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

In recent years, the ubiquitin-proteasome system (UPS) has emerged as an important regulator of stem cell function. Here we review recent findings indicating that UPS also plays critical roles in the biology of satellite cells, the muscle stem cell responsible for its maintenance and regeneration. While we focus our attention on the control of key transcriptional regulators of satellite cell function, we briefly discuss early studies suggesting the UPS participates more broadly in the regulation of satellite cell stemness and regenerative capacity.
Effects of Propofol Versus Sevoflurane on Postoperative Breast Cancer Prognosis: A Narrative Review

Perioperative interventions produce substantial biologic perturbations which are associated with the risk of recurrence after cancer surgery. The changes of tumor microenvironment caused by anesthetic drugs received increasing attention. Till now, it’s still unclear whether or not anesthetic drugs may exert positive or negative impact on cancer outcomes after surgery. Breast cancer is the most common tumor and the leading cause of cancer deaths in women. Propofol and sevoflurane are respectively the most commonly used intravenous and inhaled anesthetics. Debates regarding which of the two most commonly used anesthetics may relatively contribute to the recurrence and metastasis vulnerability of breast cancer postoperatively remain. This review aimed to provide a comprehensive view about the effect of propofol versus sevoflurane on the prognosis of breast cancer obtained from pre-clinical studies and clinical studies. Laboratory and animal studies have demonstrated that sevoflurane may enhance the recurrence and metastasis of breast cancer, while propofol is more likely to reduce the activity of breast cancer cells by attenuating the suppression of the immune system, promoting tumor cells apoptosis, and through other direct anti-tumor effects. However, retrospective clinical studies have shown contradictory results about the effects of propofol and sevoflurane on long-term survival in breast cancer patients. Furthermore, recent prospective studies did not identify significant differences between propofol and sevoflurane in breast cancer metastasis and recurrence. Therefore, more preclinical studies and randomized controlled studies are needed to guide the choice of anesthetics for breast cancer patients.
Aberrant Resting-State Functional Brain Connectivity of Insular Subregions in Obstructive Sleep Apnea

The insular cortex is a cortical regulatory area involved in dyspnea, cognition, emotion, and sensorimotor function. Previous studies reported that obstructive sleep apnea (OSA) shows insular tissue damage and abnormal functional connections for the whole insula. The insula can be divided into different subregions with distinct functional profiles, including the ventral anterior insula (vAI) participating in affective processing, dorsal anterior insula (dAI) involved in cognitive processing, and posterior insula (PI) involved in the processing of sensorimotor information. However, the functional connectivity (FC) of these insular subregions in OSA has yet to be established. Hence, the purpose of this study was to explore the resting-state FC of the insular subregions with other brain areas and its relationship with clinical symptoms of OSA. Resting-state functional magnetic resonance imaging data from 83 male OSA patients and 84 healthy controls were analyzed by whole-brain voxel-based FC using spherical seeds from six insular subregions, namely, the bilateral vAI, dAI, and PI, to identify abnormalities in the insular subregions network and related brain regions. Ultimately, the Pearson correlation analysis was carried out between the dysfunction results and the neuropsychological tests. Compared with the healthy control group, the OSA patients exhibited disturbed FC from the dAI to areas relevant to cognition, such as the bilateral cerebellum posterior lobe, superior frontal gyrus, right middle frontal gyrus and middle temporal gyrus; decreased FC from the vAI to areas linked with emotion, such as the bilateral fusiform gyrus, superior parietal lobule, precuneus and cerebellum posterior lobe; and abnormal FC from the PI to the brain regions involved in sensorimotor such as the bilateral precentral gyrus, right superior/middle temporal gyrus and left superior frontal gyrus. The linear regression result showed that the apnea-hypopnea index was positively correlated with the increased FC between the right PI and the right precuneus (after Bonferroni correlation, P < 0.001) In conclusion, the abnormal FC between insular subregions and other brain regions were related to cognitive, emotional and sensorimotor networks in OSA patients. These results may provide a new imaging perspective for further understanding of OSA-related cognitive and affective disorders.
Boosting Electrochemical Carbon Dioxide Reduction on Atomically Dispersed Nickel Catalyst

Single-atom catalysts (SACs) with metal–nitrogen (M–N) sites are one of the most promising electrocatalysts for electrochemical carbon dioxide reduction (ECO2R). However, challenges in simultaneously enhancing the activity and selectivity greatly limit the efficiency of ECO2R due to the improper interaction of reactants/intermediates on these catalytic sites. Herein, we report a carbon-based nickel (Ni) cluster catalyst containing both single-atom and cluster sites (NiNx-T, T = 500–800) through a ligand-mediated method and realize a highly active and selective electrocatalytic CO2R process. The catalytic performance can be regulated by the dispersion of Ni–N species via controlling the pyrolysis condition. Benefitting from the synergistic effect of pyrrolic-nitrogen coordinated Ni single-atom and cluster sites, NiNx-600 exhibits a satisfying catalytic performance, including a high partial current density of 61.85 mA cm−2 and a high turnover frequency (TOF) of 7,291 h−1 at −1.2 V vs. RHE, and almost 100% selectivity toward carbon monoxide (CO) production, as well as good stability under 10 h of continuous electrolysis. This work discloses the significant role of regulating the coordination environment of the transition metal sites and the synergistic effect between the isolated single-site and cluster site in enhancing the ECO2R performance.
A Novel Modified Ant Colony Optimization Algorithm by Resetting and Updating Pheromone for Vehicle Routing Problem with Time Windows

Ant Colony Optimization (ACO) algorithm is used for solving combinational optimization problem. Vehicle routing problem with time windows (VRPTW) is a well-known combinatorial problem. Many researchers apply ACO to solve VRPTW. However, Applying ACO with VRPTW encounters the problem of trapping in local optimum. The effect of trapping in local optimum originates from the pheromone of ants. This paper proposes improving ACO by resetting pheromone when trapping in local optimum occurs. The resetting pheromone is similar to run again. The results from the previous round searching are useless. Hence, this paper proposes the result from the previous round searching apply with the pheromone to guide the searching next round. The proposed algorithm was tested on fifty-six maps from a series of Solomon and provided more satisfactory results in comparison with other ACO algorithms.
Sleep Duration/Quality With Health Outcomes: An Umbrella Review of Meta-Analyses of Prospective Studies

Background To quantitatively evaluate the evidence of duration and quality of sleep as measured by multiple health outcomes. Methods This review is registered with PROSPERO, number CRD42021235587. We systematically searched three databases from inception until November 15, 2020. For each meta-analysis, the summary effect size using fixed and random effects models, the 95% confidence interval, and the 95% prediction interval were assessed; heterogeneity, evidence of small-study effects, and excess significance bias were also estimated. According to the above metrics, we evaluated the credibility of each association. Results A total of 85 meta-analyses with 36 health outcomes were included in the study. We observed highly suggestive evidence for an association between long sleep and an increased risk of all-cause mortality. Moreover, suggestive evidence supported the associations between long sleep and 5 increased risk of health outcomes (stroke, dyslipidaemia, mortality of coronary heart disease, stroke mortality, and the development or death of stroke); short sleep and increased risk of overweight and/or obesity; poor sleep quality and increased risk of diabetes mellitus and gestational diabetes mellitus. Conclusions Only the evidence of the association of long sleep with an increased risk of all-cause mortality was graded as highly suggestive. Additional studies are needed to be conducted. Systematic Review Registration: https://www.crd. york.ac. uk/PROSPERO/, identifier: CRD42021235587
Virological and Serological Characterisation of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination Between December 2020 and March 2021

Background Vaccines for coronavirus disease 2019 (COVID-19) are proving to be very effective in preventing severe illness; however, although rare, post-vaccine infections have been reported. The present study focuses on virological and serological features of 94 infections that occurred in Lazio Region (Central Italy) between 27 December 2020, and 30 March 2021, after one or two doses of mRNA BNT162b2 vaccine. Methods We evaluated clinical features, virological (viral load; viral infectiousness; genomic characterisation), and serological (anti-nucleoprotein Ig; anti-Spike RBD IgG; neutralising antibodies, nAb) characteristics of 94 post-vaccine infections at the time of diagnosis. Nasopharyngeal swabs (NPSs) and serum samples were collected in the framework of the surveillance activities on SARS-CoV-2 variants established in Lazio Region (Central Italy) and analysed at the National Institute for Infectious Diseases “L. Spallanzani” in Rome. Results The majority (92.6%) of the post-vaccine infections showed pauci/asymptomatic or mild clinical course, with symptoms and hospitalisation rate significantly less frequent in patients infected after full vaccination course as compared to patients who received a single dose vaccine. Although differences were not statistically significant, viral loads and isolation rates were lower in NPSs from patients infected after receiving two vaccine doses as compared to patients with one dose. Most cases (84%) had nAb in serum at the time of infection diagnosis, which is a sub-group of vaccinees, were found similarly able to neutralise Alpha and Gamma variants. Asymptomatic individuals showed higher nAb titres as compared to symptomatic cases (median titre: 1:120 vs. 1:40, respectively). Finally, the proportion of post-vaccine infections attributed either to Alpha and Gamma variants was similar to the proportion observed in the contemporary unvaccinated population in the Lazio region, and mutational analysis did not reveal enrichment of a defined set of Spike protein substitutions depending on the vaccination status. Conclusion Our study conducted using real-life data, emphasised the importance of monitoring vaccine breakthrough infections, through the characterisation of virological, immunological, and clinical features associated with these events, in order to tune prevention measures in the next phase of the COVID-19 pandemic.