Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives

Fibromyalgia syndrome (FMS) is a chronic illness characterized by widespread pain and other clinical and emotional symptoms. The lack of objective markers of the illness has been a persistent problem in FMS research, clinical management, and social recognition of the disease. A critical historical revision of diagnostic criteria for FMS, especially those formulated by the American College of Rheumatology (ACR), was performed. This narrative review has been structured as follows: Introduction; historical background of FMS, including studies proposing and revising the diagnostic criteria; the process of development of the ACR FMS diagnostic criteria (1990 and 2010 versions); revisions of the 2010 ACR FMS diagnostic criteria; the development of scales based on the 2010 and 2011 criteria, which could help with diagnosis and evaluation of the clinical severity of the disease, such as the Polysymptomatic Distress Scale and the FMS Survey Questionnaire; relationships of prevalence and sex ratio with the different diagnostic criteria; validity and diagnostic accuracy of the ACR FMS criteria; the issues of differential diagnosis and comorbidity; the strength and main limitations of the ACR FMS criteria; new perspectives regarding FMS diagnosis; and the impact of the novel findings in the diagnosis of FMS. It is concluded that despite the official 2010 FMS diagnostic criteria and the diagnostic proposal of 2011 and 2016, complaints from health professionals and patients continue.
A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer

Squamous cell carcinoma of the anorectal canal (SCCA) is a rare HPV-related malignancy that is steadily increasing in incidence. A high unmet need exists for patients with persistent loco-regional and metastatic disease. Axalimogene filolisbac (ADXS11-001) is an investigational immunotherapy that stimulates tumor-specific responses against HPV-associated cancers, and has demonstrated benefit in metastatic cervical cancer. We conducted this single-arm, multicenter, phase 2 trial in patients with persistent/recurrent, loco-regional or metastatic SCCA. Patients received ADXS11-001, 1 × 109 colony-forming units intravenously every 3 weeks. A Simon 2-stage design was used to test primary co-endpoints of overall response rate (ORR) and 6-month progression-free survival (PFS) rate. Study would proceed to full enrollment if ORR ≥ 10% or 6-month PFS rate ≥ 20%. Thirty-six patients were treated; 29 patients were evaluable for response. One patient had a prolonged partial response (3.4% ORR). The 6-month PFS rate was 15.5%. Grade 3 adverse event were noted in 10 patients, with the majority being cytokine-release symptoms; one grade 4 adverse event was noted. No grade 5 adverse events occurred. ADXS11-001 was safe and well-tolerated in patients with SCCA. However, this study did not meet either primary endpoint. ADXS11-001 may be more beneficial when administered in combination with other cytotoxic or targeted agents.
Micropropagation of thornless trailing blackberry (Rubus sp.) by axillary bud explants.

The purpose of this study was to establish best condition for in vitro propagation of thornless trailing blackberry (Rubus sp.). Axillary buds were used as explants. After sterilization, explants were placed into MS medium supplemented with 2 mg.l{-1} BA. Two weeks after that, in shoot proliferation stage, 12 culture media containing MS supplemented with 3 concentrations of BA (0, 2 and 3 mg.l{-1}), alone or in combination with GA{3} (0, 0.2, 0.5 and 1 mg.l{-1}) were compared. The greatest number of shoots with average of 3.33 and the maximum shoot length with average of 5.87 cm were produced in medium containing 2 mg.l{-1} BA and 0.5 mg.l{-1} GA{3}. In the rooting experiment, rooting medium comprised MS medium in combination with different concentrations of IBA (0, 0.5, 1 and 2 mg.l{-1}). A concentration of 2 mg.l{-1} IBA gave a greater number of roots and maximum root length. In this medium four roots with root length average of 7.83 cm were produced.
YAP Mediates Hair Cell Regeneration in Balance Organs of Chickens, But LATS Kinases Suppress Its Activity in Mice

Loss of sensory hair cells causes permanent hearing and balance deficits in humans and other mammals, but for nonmammals such deficits are temporary. Nonmammals recover hearing and balance sensitivity after supporting cells proliferate and differentiate into replacement hair cells. Evidence of mechanical differences between those sensory epithelia and their supporting cells prompted us to investigate whether the capacity to activate YAP, an effector in the mechanosensitive Hippo pathway, correlates with regenerative capacity in acceleration-sensing utricles of chickens and mice of both sexes. After hair cell ablation, YAP accumulated in supporting cell nuclei in chicken utricles and promoted regenerative proliferation, but YAP remained cytoplasmic and little proliferation occurred in mouse utricles. YAP localization in supporting cells was also more sensitive to shape change and inhibition of MST1/2 in chicken utricles than in mouse utricles. Genetic manipulations showed that in vivo expression of the YAP-S127A variant caused robust proliferation of neonatal mouse supporting cells, which produced progeny that expressed hair cell markers, but proliferative responses declined postnatally. Expression of YAP-5SA, which more effectively evades inhibitory phosphorylation, resulted in TEAD-dependent proliferation of striolar supporting cells, even in adult utricles. Conditional deletion of LATS1/2 kinases abolished the inhibitory phosphorylation of endogenous YAP and led to striolar proliferation in adult mouse utricles. The findings suggest that damage overcomes inhibitory Hippo signaling and facilitates regenerative proliferation in nonmammalian utricles, whereas constitutive LATS1/2 kinase activity suppresses YAP-TEAD signaling in mammalian utricles and contributes to maintaining the proliferative quiescence that appears to underlie the permanence of sensory deficits. SIGNIFICANCE STATEMENT Loud sounds, ototoxic drugs, infections, and aging kill sensory hair cells in the ear, causing irreversible hearing loss and balance deficits for millions. In nonmammals, damage evokes shape changes in supporting cells, which can divide and regenerate hair cells. Such shape changes are limited in mammalian ears, where supporting cells develop E-cadherin-rich apical junctions reinforced by robust F-actin bands, and the cells fail to divide. Here, we find that damage readily activates YAP in supporting cells within balance epithelia of chickens, but not mice. Deleting LATS kinases or expressing YAP variants that evade LATS-mediated inhibitory phosphorylation induces proliferation in supporting cells of adult mice. YAP signaling eventually may be harnessed to overcome proliferative quiescence that limits regeneration in mammalian ears.
A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer

Purpose We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. Materials and Methods In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. Results The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in four and two patients, respectively, with no treatment-related deaths. Conclusion Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.
Decidual Granulomata of Unclear Significance

Granulomatous inflammation is a histologic finding with a relatively wide variety of causes. In general, considerations include infectious etiologies, autoimmune conditions, or foreign body reactions. Granulomatous inflammation is uncommonly seen in the placenta. We present a unique case of a young woman with preterm labor and rupture of membranes whose placenta demonstrated perivascular decidual granulomata in the membranes and the basal plate.
Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder

Significance Autism is a poorly understood brain disorder of childhood onset. It is characterized by social impairments and diagnosed behaviorally. Early diagnosis fosters better developmental outcomes through behavioral intervention. However, long clinic wait times to undergo behavioral evaluation contribute to delayed diagnoses and treatments. Emerging evidence indicates that low cerebrospinal fluid concentration of the “social” neuropeptide vasopressin is a marker of social impairment in children with autism. Here we report that cerebrospinal fluid vasopressin concentration is significantly lower in newborns diagnosed with autism later in childhood. These preliminary findings suggest that a biomarker of autism may be present before behavioral symptoms emerge. If replicated, this approach could be useful for assessing autism risk and facilitating early intervention in high-risk individuals. Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the “social” neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-old febrile infants (n = 913) and subsequently archived at −70 °C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.
Hierarchical Optimal Synchronization for Linear Systems via Reinforcement Learning: A Stackelberg–Nash Game Perspective

Considering the fact that in the real world, a certain agent may have some sort of advantage to act before others, a novel hierarchical optimal synchronization problem for linear systems, composed of one major agent and multiple minor agents, is formulated and studied in this article from a Stackelberg–Nash game perspective. The major agent herein makes its decision prior to others, and then, all the minor agents determine their actions simultaneously. To seek the optimal controllers, the Hamilton–Jacobi–Bellman (HJB) equations in coupled forms are established, whose solutions are further proven to be stable and constitute the Stackelberg–Nash equilibrium. Due to the introduction of the asymmetric roles for agents, the established HJB equations are more strongly coupled and more difficult to solve than that given in most existing works. Therefore, we propose a new reinforcement learning (RL) algorithm, i.e., a two-level value iteration (VI) algorithm, which does not rely on complete system matrices. Furthermore, the proposed algorithm is shown to be convergent, and the converged values are exactly the optimal ones. To implement this VI algorithm, neural networks (NNs) are employed to approximate the value functions, and the gradient descent method is used to update the weights of NNs. Finally, an illustrative example is provided to verify the effectiveness of the proposed algorithm.
Subthreshold Electrical Stimulation for Controlling Protein-Mediated Impedance Increases in Platinum Cochlear Electrode

Objective: This study evaluated subthreshold biphasic stimulation pulses as a strategy to stabilize electrode impedance via control of protein adsorption. Following implantation, cochlear electrodes undergo impedance fluctuations thought to be caused by protein adsorption and/or inflammatory responses. Impedance increases can impact device power consumption, safe charge injection limits, and long-term stability of electrodes. Methods: Protein-mediated changes in polarization impedance (Zp) were measured by voltage transient responses to biphasic current pulses and electrochemical impedance spectroscopy, with and without protein solutions. Four subthreshold stimulation regimes were studied to assess their effects on protein adsorption and impedance; (1) symmetric charge-balanced pulses delivered continuously, (2) at 10% duty cycle, (3) at 1% duty cycle, and (4) an asymmetric charge balanced pulse delivered continuously with a cathodic phase twice as long as the anodic phase. Results: The Zp of electrodes incubated in protein solutions without stimulation for 2 h increased by between ∼28% and ∼55%. Subthreshold stimulation reduced the rate at which impedance increased following exposure to all protein solutions. Decreases in Zp were dependent on the type of protein solution and the stimulation regime. Subthreshold stimulation pulses were more effective when delivered continuously compared to 1% and 10% duty cycles. Conclusion: These results support the potential of subthreshold stimulation pulses to mitigate protein-mediated increase in impedance. Significance: This research highlights the potential of clinically translatable stimulation pulses to mitigate perilymph protein adsorption on cochlear electrodes, a key phenomenon precursor of the inflammatory response.
Neural Immune Communication in the Control of Host-Bacterial Pathogen Interactions in the Gastrointestinal Tract

The orchestration of host immune responses to enteric bacterial pathogens is a complex process involving the integration of numerous signals, including from the nervous system. Despite the recent progress in understanding the contribution of neuroimmune interactions in the regulation of inflammation, the mechanisms and effects of this communication during enteric bacterial infection are only beginning to be characterized. As part of this neuroimmune communication, neurons specialized to detect painful or otherwise noxious stimuli can respond to bacterial pathogens. ABSTRACT The orchestration of host immune responses to enteric bacterial pathogens is a complex process involving the integration of numerous signals, including from the nervous system. Despite the recent progress in understanding the contribution of neuroimmune interactions in the regulation of inflammation, the mechanisms and effects of this communication during enteric bacterial infection are only beginning to be characterized. As part of this neuroimmune communication, neurons specialized to detect painful or otherwise noxious stimuli can respond to bacterial pathogens. Highlighting the complexity of these systems, the immunological consequences of sensory neuron activation can be either host adaptive or maladaptive, depending on the pathogen and organ system. These are but one of many types of neuroimmune circuits, with the vagus nerve and sympathetic innervation of numerous organs now known to modulate immune cell function and therefore dictate immunological outcomes during health and disease. Here, we review the evidence for neuroimmune communication in response to bacterial pathogens, and then discuss the consequences to host morbidity and mortality during infection of the gastrointestinal tract.
A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma

There is indication that nutritional supplements protect retinal cells from degeneration. In a previous study, we demonstrated that dietary supplementation with an association of forskolin, homotaurine, spearmint extract and B vitamins efficiently counteracts retinal dysfunction associated with retinal ganglion cell (RGC) death caused by optic nerve crush. We extended our investigation on the efficacy of dietary supplementation with the use of a mouse model in which RGC degeneration depends as closely as possible on intraocular pressure (IOP) elevation. In this model, injecting the anterior chamber of the eye with methylcellulose (MCE) causes IOP elevation leading to RGC dysfunction. The MCE model was characterized in terms of IOP elevation, retinal dysfunction as determined by electrophysiological recordings, RGC loss as determined by brain-specific homeobox/POU domain protein 3A immunoreactivity and dysregulated levels of inflammatory and apoptotic markers. Except for IOP elevation, dysfunctional retinal parameters were all recovered by dietary supplementation indicating the involvement of non-IOP-related neuroprotective mechanisms of action. Our hypothesis is that the diet supplement may be used to counteract the inflammatory processes triggered by glial cell activation, thus leading to spared RGC loss and the preservation of visual dysfunction. In this respect, the present compound may be viewed as a potential remedy to be added to the currently approved drug therapies for improving RGC protection.
Neonatal outcomes of two‐step delivery in low‐risk pregnancy: A prospective observational study

Extraction of the fetal body is typically performed immediately after delivery of the head in Western obstetric care. Reports justifying immediate extraction are few. Two‐step delivery entails waiting for the next uterine contraction after delivery of the head. The present study evaluates neonatal asphyxia and respiratory impairment in two‐step delivery using the head‐to‐body delivery interval.
A Health System Response to COVID‐19 in Long‐Term Care and Post‐Acute Care: A Three‐Phase Approach

The Seattle, WA, area was ground zero for coronavirus disease 2019 (COVID‐19). Its initial emergence in a skilled nursing facility (SNF) not only highlighted the vulnerability of its patients and residents, but also the limited clinical support that led to national headlines. Furthermore, the coronavirus pandemic heightened the need for improved collaboration among healthcare organizations and local and state public health.
Approximations to the Voice of a Cochlear Implant: Explorations With Single-Sided Deaf Listeners

Fourteen single-sided deaf listeners fit with an MED-EL cochlear implant (CI) judged the similarity of clean signals presented to their CI and modified signals presented to their normal-hearing ear. The signals to the normal-hearing ear were created by (a) filtering, (b) spectral smearing, (c) changing overall fundamental frequency (F0), (d) F0 contour flattening, (e) changing formant frequencies, (f) altering resonances and ring times to create a metallic sound quality, (g) using a noise vocoder, or (h) using a sine vocoder. The operations could be used singly or in any combination. On a scale of 1 to 10 where 10 was a complete match to the sound of the CI, the mean match score was 8.8. Over half of the matches were 9.0 or higher. The most common alterations to a clean signal were band-pass or low-pass filtering, spectral peak smearing, and F0 contour flattening. On average, 3.4 operations were used to create a match. Upshifts in formant frequencies were implemented most often for electrode insertion angles less than approximately 500°. A relatively small set of operations can produce signals that approximate the sound of the MED-EL CI. There are large individual differences in the combination of operations needed. The sound files in Supplemental Material approximate the sound of the MED-EL CI for patients fit with 28-mm electrode arrays.
Injury risk and injury incidence rates in crossfit: a brief review.

INTRODUCTION Despite completing complex movements under cardiovascular and muscular fatigued conditions, CrossFit suggested safety of participants is one of the most important factors to consider. Therefore, the aim of this brief review is to provide an overview of the injury incidence and incidence rates reported in the current literature as well as to assess the injury risks associated with CrossFit. EVIDENCE ACQUISITION Research papers were searched using the following databases: Scopus, SPORTDiscus, Web of Science, PubMed, and MEDLINE. The search identified 718 potential articles across all databases. After the application of inclusion criteria, a total of 14 articles were included in this review. EVIDENCE SYNTHESIS The shoulder, spine, and knee are the most commonly injured areas in CrossFit. Injury incidence of each study ranges from 12.8-73.5% and reported injury rates ranging from 0.27-3.3/1000 training hours. CONCLUSIONS Reported findings in the current literature would suggest CrossFit has a relatively low injury risk. The current review highlights three important factors associated with injury incidence and incidence rates in CrossFit: 1) training frequency, 2) duration of CrossFit experience, 3) individuals that compete in CrossFit competitions. Due to recall bias and selection bias further research is warranted over a longitudinal prospective study. Additionally, further research is needed to investigate mechanisms of injury and the relationship between training load and injury risk in CrossFit.