Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of salvage surgery for recurrent or residual head and neck squamous cell carcinoma.

OBJECTIVE Concomitant chemoradiation therapy is a standard treatment for head and neck cancer. Thus, salvage surgery has become a necessary treatment. The aim of the study was to evaluate the results of salvage surgery by each site of the head and neck, especially the oropharynx, hypopharynx and larynx. METHODS This was a retrospective, single-institute study. The primary endpoint was overall survival. Secondary endpoints were disease-free survival, the locoregional control rate after salvage surgery, the indication rate for salvage surgery, the reasons for contraindications to salvage surgery, the post-operative complication rate and the predictors of survival. RESULTS Three-year overall survival after salvage surgery was 58.8% in the salvage surgery group and 8.59% in the other treatment group (P < 0.0001). Regarding overall survival and disease-free survival after salvage surgery, there was no difference among sites. Regarding locoregional control rate among sites, there was no significant difference. The oropharyngeal cancer group had the lowest rate of salvage primary resection. Surgical margin and local and regional recurrence or residual disease were predictors on univariate and multivariate analyses. CONCLUSIONS Salvage surgery is effective for recurrent or residual cases after concomitant chemoradiation therapy. For oropharyngeal cancer, local control is important, and for oropharyngeal cancer and hypopharyngeal cancer, distant metastasis is important.
Error Augmentation in Immersive Virtual Reality for Bimanual Upper-Limb Rehabilitation in Individuals With and Without Hemiplegic Cerebral Palsy

With more readily available commercial immersive virtual reality (VR) technologies, the potential of new feedback strategies as tools to facilitate motor rehabilitation should be investigated. Augmented feedback or error augmentation (EA) can easily be shown in a virtual environment. Here, visual EA provided via immersive VR was tested for its effectiveness to improve bimanual symmetry in a reaching task. A single-session crossover design was used to test two training cases, with or without EA. With EA, the distance between hands in the forward direction was augmented. Participants were recruited from typically developing (TD) populations (n = 12, ages 13–21) and performed in an adapted environment with an initial asymmetry between limbs. Also, five participants with hemiplegic cerebral palsy (CP) (ages 14–21, MACS I-III) completed the study. Among TD participants, a significantly larger change in symmetry in the adapted environment was shown after EA than training without EA (F (1, 10) = 9.64, p = 0.01). Each participant in the CP group also improved more after EA training (8.8–103.7)%, such that they achieved lower symmetry error after training with EA. As participants in both groups adapted more symmetrically with EA, beneficial changes from this training method could be evaluated in future studies for longer-term functional changes.
JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression

Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates almost all immune regulatory processes, including those that are involved in tumor cell recognition and tumor-driven immune escape. Antitumor immune responses are largely driven by STAT1 and STAT2 induction of type I and II interferons (IFNs) and the downstream programs IFNs potentiate. Conversely, STAT3 has been widely linked to cancer cell survival, immunosuppression, and sustained inflammation in the tumor microenvironment. The discovery of JAK-STAT cross-regulatory mechanisms, post-translational control, and non-canonical signal transduction has added a new level of complexity to JAK-STAT governance over tumor initiation and progression. Endeavors to better understand the vast effects of JAK-STAT signaling on antitumor immunity have unearthed a wide range of targets, including oncogenes, miRNAs, and other co-regulatory factors, which direct specific phenotypical outcomes subsequent to JAK-STAT stimulation. Yet, the rapidly expanding field of therapeutic developments aimed to resolve JAK-STAT aberrations commonly reported in a multitude of cancers has been marred by off-target effects. Here, we discuss JAK-STAT biology in the context of immunity and cancer, the consequences of pathway perturbations and current therapeutic interventions, to provide insight and consideration for future targeting innovations.
Calcitriol Elevation is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors.

BACKGROUND Hypercalcemia of malignancy (HCM) is a common complication of advanced cancer. Parathyroid hormone (PTH)-independent HCM may be mediated through different mechanisms: 1) humoral HCM, caused by the secretion of parathyroid hormone-related peptide (PTHrP), 2) local osteolysis due to metastatic lesions, and, 3) calcitriol-mediated hypercalcemia. Calcitriol-mediated HCM in patients with non-lymphomatous solid tumors is thought to be rare. METHODS We performed a retrospective chart review from 2008-2017 to characterize further patients at our institution with solid tumors who had HCM with concomitant elevations in calcitriol. Patients with PTH dependent hypercalcemia and patients with evidence of granulomatous disease were excluded as were patients with hematologic malignancies. We hypothesized that patients with HCM and elevated calcitriol levels would respond less favorably to treatment with antiresorptive therapy compared to patients with HCM but without calcitriol elevation. We also aimed to assess mortality and determine if PTHrP and phosphorus levels correlate with calcitriol, as both factors may alter calcitriol levels. RESULTS Of 101 eligible patients, calcitriol was elevated in 45 (45%). PTHrP was elevated in 76% of patients with elevated calcitriol compared to 52% of patients without calcitriol elevation. The mean PTHrP value did not differ between patients with HCM and elevated calcitriol (36.3 ± 22 pg/mL) and those without calcitriol elevation (37.4 ± 19 pg/mL). Those with elevated calcitriol levels generally did not respond completely to antiresorptive treatment (80% incomplete response rate) while most patients without an elevation in calcitriol responded well to antiresorptive treatment (78% response rate: p <0.001). There was no significant difference in the percentage of patients with metastatic bone disease among the 2 groups (49% vs. 55%, respectively). There was no difference in mortality between the 2 groups (p=0.14). A weak but significant negative correlation was found between phosphorus and calcitriol (Pearson's r = -0.261, p=0.016). This correlation was only significant in patients without calcitriol elevation. (Pearson's r = -0.4, p=0.0082). Also, a significant negative correlation was found between PTHrP and phosphorus, again only in patients without calcitriol elevation. DISCUSSION In the setting of HCM, patients with calcitriol elevation are much less likely to respond to antiresorptive therapy than patients without calcitriol elevation. Since calcitriol elevation did not appear to be correlated with hypophosphatemia or elevated PTHrP, it would appear that calcitriol production under these conditions is autonomous, and not subject to normal physiological controls. These observations indicate that calcitriol elevations in patients with HCM have clinical significance.
High-Frequency Multipulse, Plane-Wave Acoustic Contrast Imaging

Multipulse (MP) ultrasound contrast agent (UCA) imaging is a method to increase the contrast-to-background (CBR) ratio in regions of blood flow. Plane-wave imaging allows high frame rates, and with high-frequency ultrasound, fine-spatial and temporal resolution. MP and plane-wave imaging have not been applied to high-frequency ultrasound. Here, an 18-MHz linear array was employed to implement the MP methods of pulse inversion (PI) and amplitude modulation (AM) using high-speed, multiangle, compound plane-wave imaging. A flow of the UCA DEFINITY© at a dilution ratio of 2000:1 circulating through a 2-mm-diameter flow channel in a tissue-mimicking phantom was used to characterize CBR and compared with cases of standard, multiangle compound plane-wave imaging. The relative improvement of PI and AM versus standard plane-wave imaging ranged from 5 to 10 dB. The CBR was observed to be stable over a 60-min time duration for a 2000:1 dilution ratio and a 2000:1 dilution ratio provided an optimal CBR.
Biobased Composites from Biobased-Polyethylene and Barley Thermomechanical Fibers: Micromechanics of Composites

The cultivation of cereals like rye, barley, oats, or wheat generates large quantities of agroforestry residues, which reaches values of around 2066 million metric tons/year. Barley straw alone represents 53%. In this work, barley straw is recommended for the production of composite materials in order to add value to this agricultural waste. First of all, thermomechanical (TMP) fibers from barley straw are produced and later used to reinforce bio-polyethylene (BioPE) matrix. TMP barley fibers were chemically and morphologically characterized. Later, composites with optimal amounts of coupling agent and fiber content ranging from 15 to 45 wt % were prepared. The mechanical results showed the strengthening and stiffening capacity of the TMP barley fibers. Finally, a micromechanical analysis is applied to evaluate the quality of the interface and to distinguish how the interface and the fiber morphology contributes to the final properties of these composite materials.
Relationship among Activities of Daily Living, Nutritional Status, and 90 Day Readmission in Elderly Patients with Heart Failure

Purpose: This investigation aimed to examine the relationship among activities of daily living (ADL), nutritional status and 90-day hospital readmission in elderly heart failure (HF) patients. Methods: Participants were selected from 634 HF patients consecutively hospitalized at one institution. We investigated patient characteristics, ADL (motor and cognitive items of Functional Independence Measure (FIM)) and nutritional status (Geriatric Nutritional Risk Index (GNRI)). Data were analyzed using unpaired t-test, χ2 test, Cox proportional hazard model, and Kaplan-Meier method. Results: The 169 participants that met inclusion criteria were divided into two groups based on hospital readmission within 90 days of discharge. Body mass index (BMI) (p = 0.03), hemoglobin (p = 0.047), GNRI (p = 0.02) and motor-FIM (p = 0.007) were significantly different between the readmission (n = 31) and non-readmission (n = 138) groups. After Cox proportional hazard model analysis, GNRI (HR: 0.96; p = 0.048) and motor-FIM (HR: 0.97; p = 0.03) scores remained statistically significant. Participants were then classified into four groups based on a previous study’s cut-off values of prognosis for GNRI and motor-FIM. Readmission avoidance rate was significantly lower (p = 0.002) in the group with GNRI <92 and motor FIM <75. Conclusions: This study showed that motor-FIM and GNRI scores for hospitalized elderly HF patients were predictors of readmission within 90 days of discharge.
Mechanism for antigenic peptide selection by endoplasmic reticulum aminopeptidase 1

Significance Endoplasmic reticulum aminopeptidase 1 (ERAP1), an enzyme important for regulating adaptive immune responses, is an emerging target for immunotherapy applications. One of the hallmarks of ERAP1 is that it must be able to select substrates out of hundreds of thousands of possible ones. An incomplete understanding of how it performs this selection has been a major barrier to predicting and manipulating its effects on the immune response. We solved high-resolution crystal structures of ERAP1 with substrate analogs, which, along with biochemical and computational analysis, shed light on the mechanism that ERAP1 uses to select its substrates. Our structures constitute an important framework for better predicting epitope selection and immunodominance. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that optimizes the peptide cargo of major histocompatibility class I (MHC-I) molecules and regulates adaptive immunity. It has unusual substrate selectivity for length and sequence, resulting in poorly understood effects on the cellular immunopeptidome. To understand substrate selection by ERAP1, we solved 2 crystal structures of the enzyme with bound transition-state pseudopeptide analogs at 1.68 Å and 1.72 Å. Both peptides have their N terminus bound at the active site and extend away along a large internal cavity, interacting with shallow pockets that can influence selectivity. The longer peptide is disordered through the central region of the cavity and has its C terminus bound in an allosteric pocket of domain IV that features a carboxypeptidase-like structural motif. These structures, along with enzymatic and computational analyses, explain how ERAP1 can select peptides based on length while retaining the broad sequence-specificity necessary for its biological function.
Ubiquitin C‐terminal hydrolase‐L1 has prognostic relevance and is a therapeutic target for high‐grade neuroendocrine lung cancers

High‐grade neuroendocrine lung cancer (HGNEC), which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is a rapidly proliferating, aggressive form of lung cancer. The initial standard chemotherapeutic regimens of platinum doublets are recommended for SCLC and have been frequently used for LCNEC. However, there are currently no molecularly targeted agents with proven clinical benefit for this disease. The deubiquitinating enzyme ubiquitin C‐terminal hydrolase‐L1 (UCHL1) is a neuroendocrine cell‐specific product that is known as a potential oncogene in several types of cancer, but little is known about the biological function of UCHL1 and its therapeutic potential in HGNEC. In this study, we found that preclinical efficacy evoked by targeting UCHL1 was relevant to prognosis in HGNEC. UCHL1 was found to be expressed in HGNEC, particularly in cell lines and patient samples of SCLC, and the combined use of platinum doublets with selective UCHL1 inhibitors improved its therapeutic response in vitro. Immunohistochemical expression of UCHL1 was significantly associated with postoperative survival in patients with HGNEC and contributed towards distinguishing SCLC from LCNEC. Circulating extracellular vesicles (EV), including exosomes isolated from lung cancer cell lines and serum from early‐stage HGNEC, were verified by electron microscopy and nanoparticle tracking analysis. Higher levels of UCHL1 mRNA in EV were found in the samples of patients with early‐stage HGNEC than those with early‐stage NSCLC and healthy donors’ EV. Taken together, UCHL1 may be a potential prognostic marker and a promising druggable target for HGNEC.
Towards elimination of measles and rubella in Italy: Progress and challenges

Introduction In the WHO European Region, endemic transmission of measles and rubella had been interrupted by 37 and 42 of the 53 member states (MSs), respectively, by 2018. Sixteen MSs are still endemic for measles, 11 for rubella and nine for both diseases, the latter including Italy. Elimination is documented by each country’s National Verification Committee (NVC) through an annual status update (ASU). Objective By analysing data used to produce the ASUs, we aimed to describe the advances made by Italy towards elimination of measles and rubella. Moreover, we propose a set of major interventions that could facilitate the elimination process. Methods A total of 28 indicators were identified within the six core sections of the ASU form and these were evaluated for the period 2013–2018. These indicators relate to the incidence of measles/rubella; epidemiological investigation of cases; investigation of outbreaks; performance of the surveillance system; population immunity levels; and implementation of supplemental immunization activities (SIAs). Results From 2013 to 2018, epidemiological and laboratory analyses of measles cases in Italy improved substantially, allowing timely investigation in 2017 and 2018 of most outbreak and sporadic cases and identification of the majority of genotypic variants. Moreover, since 2017, vaccination coverage has increased significantly. Despite these improvements, several areas of concern emerged, prompting the following recommendations: i) improve outbreak monitoring; ii) strengthen the MoRoNet network; iii) increase the number of SIAs; iv) reinforce vaccination services; v) maintain regional monitoring; vi) design effective communication strategies; vii) foster the role of general practitioners and family paediatricians. Conclusions The review of national ASUs is a crucial step to provide the NVC with useful insights into the elimination process and to guide the development of targeted interventions. Against this background, the seven recommendations proposed by the NVC have been shared with the Italian Ministry of Health and the Technical Advisory Group on measles and rubella elimination and have been incorporated into the new Italian Elimination Plan 2019–2023 as a technical aid to facilitate the achievement of disease elimination goals.
Evoked potentials as a biomarker of remyelination

Significance Remyelination is a critical therapeutic target in MS that will restore function and protect demyelinated axons. Clinical trials of putative remyelination-promoting drugs depend on valid, robust, and noninvasive outcome measures. To date, MRI has failed to provide outcome metrics sufficiently sensitive and specific to remyelination. Optic neuritis is a common symptom of MS and visual evoked potentials (VEPs) have been proposed to identify demyelination during acute disease and subsequent remyelination, but this is unproven. Here, we use an animal model with severe optic nerve demyelination and subsequent remyelination to show that the VEP latency truly measures these myelin sheath changes. Hence, the VEP can be used as an outcome measure in future MS trials in which remyelination is the goal. Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.
Psychiatric Distress as a Common Risk Factor for Tinnitus and Joint Pain: A National Population-Based Survey

Objectives This study aimed to investigate the relationship between tinnitus and joint pain from representative samples of Koreans. Methods The demographics and the responses to a questionnaire about tinnitus and joint pain severity and mental health status of adults aged ≥50 years in the 2010–2012 Korean National Health and Nutrition Examination Survey were analyzed. Results Among 9,032 individuals, 26.7% reported experiencing tinnitus within the past year. Participants with tinnitus were more frequently older, hearing loss, and had lower education levels, income, and body weight. Participants with regular exercise and sleep had a lower tinnitus prevalence. The incidences of stress, depressed mood, and suicidal ideation were significantly higher in the tinnitus group and participants with joint pain. The rates of participants with tinnitus according to the number of joint pain sites (zero, one, two, and three) was 22.1%, 31.4%, 33.3%, and 44.2%, and those of participants with severely annoying tinnitus according to the number of joint pain sites (zero, one, two, and three) were 3.3%, 6.8%, 7.9%, and 10.7%, respectively. Conclusion Tinnitus prevalence and severity were significantly related to joint pain, and both conditions were related to psychiatric distress. Thus, the authors suggest that psychiatric distress as a common risk factor for tinnitus and joint pain should be considered when deciding treatment strategies and in guiding public health policy.
Process and Structure: Service Satisfaction and Recommendation in a Community-based Elderly Meal Service in Shanghai

ABSTRACT Informed by Donabedian’s quality-of-care framework, this study aims to examine elderly clients’ service satisfaction and service recommendation for community-based meal services in Shanghai. We analyzed secondary survey data from randomly sampled elderly clients of a community-based meal service in the old Jing’an District in Shanghai (N= 690). Quality of food and caregivers’ attitudes were key to respondents’ service recommendation while tidiness of tableware and interactions with caregivers were positively related to their service satisfaction. Overlaps and differences between structure and process factors are discussed. We also provide tailored policy recommendations.
Health assessment of juvenile green turtles in southern São Paulo State, Brazil: a hematologic approach

We assessed the health status and hematologic and blood chemistry values of 48 juvenile green turtles (Chelonia mydas) on the southeastern coast of Brazil (25°S 48°W). We investigated the impact of size and weight, nutritional condition, and presence of epibionts and fibropapilloma tumors. Nutritional status was good for 39 animals; these animals had higher serum albumin, cholesterol, and phosphorus concentrations than 9 animals with a fair nutritional score. Reference values for hematology and biochemistry were calculated for 39 individuals without fibropapillomas (FPs). Turtles with epibionts (n = 33) had lower hemoglobin (Hb) than turtles without epibionts (n = 15; t = −2.09, p = 0.04), and the area occupied by epibionts was positively correlated with the white blood cell count (r = 0.37, p = 0.03). FP turtles had significantly lower hematocrit (Hct), Hb, and red blood cell (RBC) counts than non-FP turtles; serum albumin and cholesterol were higher in non-FP than FP turtles. A negative correlation between curved carapace length (CCL) and Hct (r = −0.51, p = 0.0002) and RBC (r = −0.47, p = 0.0007), and between serum cholesterol, sodium, and uric acid and CCL (r = −0.53, p = 0.0001; r = −0.38, p = 0.007; r = −0.35, p = 0.014, respectively) were identified. The health of turtles appears to deteriorate as they get larger, which manifests in more FPs, decreased body condition, and systemic physiologic changes consistent with chronic disease including lower Hct, RBC counts, serum cholesterol, sodium, and uric acid.