Miracle-dz/UniFAR-FTUs huggingface dataset:
Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D–cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.
A Comparison of the Affectiva iMotions Facial Expression Analysis Software With EMG for Identifying Facial Expressions of Emotion

Human faces express emotions, informing others about their affective states. In order to measure expressions of emotion, facial Electromyography (EMG) has widely been used, requiring electrodes and technical equipment. More recently, emotion recognition software has been developed that detects emotions from video recordings of human faces. However, its validity and comparability to EMG measures is unclear. The aim of the current study was to compare the Affectiva Affdex emotion recognition software by iMotions with EMG measurements of the zygomaticus mayor and corrugator supercilii muscle, concerning its ability to identify happy, angry and neutral faces. Twenty participants imitated these facial expressions while videos and EMG were recorded. Happy and angry expressions were detected by both the software and by EMG above chance, while neutral expressions were more often falsely identified as negative by EMG compared to the software. Overall, EMG and software values correlated highly. In conclusion, Affectiva Affdex software can identify facial expressions and its results are comparable to EMG findings.
Immune Checkpoint Markers in Neuroendocrine Carcinoma of the Digestive System

Digestive system neuroendocrine carcinomas (NECs) are rare neoplasms originating from neuroendocrine cells with a poor prognosis and limited effective treatments. Programmed cell death protein 1/ligand 1 (PD-1/PD-L1) blockade has been used in the management of more than 10 solid tumors and has achieved promising clinical outcomes. PD-L1 expression, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) are all verified biomarkers that can predict the response to anti-PD-1/PD-L1 therapy. Here, we investigated PD-L1 expression and immune cell infiltration density by immunohistochemical (IHC) staining of tumor samples from 33 patients with digestive system NECs. Tumor and paratumor normal samples from 31 of these patients underwent whole-exome sequencing to evaluate TMB and the MSI-high (MSI-H) status. In total, 29.0% of digestive system NECs had positive PD-L1 expression according to the tumor proportion score (TPS). Infiltration of CD3+, CD8+, and CD68+ cells was observed in 69.7, 27.3, and 54.5% of patients, respectively. The TMB value for patients sequenced ranged from 0.57 to 11.75 mutations/Mb, with a median of 5.68 mutations/Mb. mSINGS, MSIsensor, and MSIseq were used to analyze the MSI status according to the sequencing data, and in our evaluation, no MSI-H status was detected. Our data might indicate a limited potential of anti-PD-1/PD-L1 monotherapy in digestive system NECs, although clinical trials are warranted.
Differential Reorganization of SMA Subregions After Stroke: A Subregional Level Resting-State Functional Connectivity Study

Background and Purpose: The human supplementary motor area (SMA) contains two functional subregions of the SMA proper and preSMA; however, the reorganization patterns of the two SMA subregions after stroke remain uncertain. Meanwhile, a focal subcortical lesion may affect the overall functional reorganization of brain networks. We sought to identify the differential reorganization of the SMA subregions after subcortical stroke using the resting-state functional connectivity (rsFC) analysis. Methods: Resting-state functional MRI was conducted in 25 patients with chronic capsular stroke exhibiting well-recovered global motor function (Fugl–Meyer score >90). The SMA proper and preSMA were identified by the rsFC-based parcellation, and the rsFCs of each SMA subregion were compared between stroke patients and healthy controls. Results: Despite common rsFC with the fronto-insular cortex (FIC), the SMA proper and preSMA were mainly correlated with the sensorimotor areas and cognitive-related regions, respectively. In stroke patients, the SMA proper and preSMA exhibited completely different functional reorganization patterns: the former showed increased rsFCs with the primary sensorimotor area and caudal cingulate motor area (CMA) of the motor execution network, whereas the latter showed increased rsFC with the rostral CMA of the motor control network. Both of the two SMA subregions showed decreased rsFC with the FIC in stroke patients; the preSMA additionally showed decreased rsFC with the prefrontal cortex (PFC). Conclusion: Although both SMA subregions exhibit functional disconnection with the cognitive-related areas, the SMA proper is implicated in the functional reorganization within the motor execution network, whereas the preSMA is involved in the functional reorganization within the motor control network in stroke patients.
Generalized Mittag-Leffler Type Function: Fractional Integrations and Application to Fractional Kinetic Equations

The generalized fractional integrations of the generalized Mittag-Leffler type function (GMLTF) are established in this paper. The results derived in this paper generalize many results available in the literature and are capable of generating several applications in the theory of special functions. The solutions of a generalized fractional kinetic equation using the Sumudu transform is also derived and studied as an application of the GMLTF.
Nitrate Transporter Gene Expression and Kinetics of Nitrate Uptake by Populus × canadensis ‘Neva’ in Relation to Arbuscular Mycorrhizal Fungi and Nitrogen Availability

Plants and other organisms in the ecosystem compete for the limited nitrogen (N) in the soil. Formation of a symbiotic relationship with arbuscular mycorrhizal fungi (AMF) may influence plant competitiveness for N. However, the effects of AMF on plant nitrate (NO3–) uptake capacity remain unknown. In this study, a pot experiment was conducted to investigate the effects of N application and Rhizophagus irregularis inoculation on the root absorbing area, uptake kinetics of NO3–, and the expression of NO3– transporter (NRT) genes in Populus × canadensis ‘Neva’. The results showed that R. irregularis colonized more than 70% of the roots of the poplar and increased root active absorbing area/total absorbing area. The uptake kinetics of NO3– by poplar fitted the Michaelis–Menten equation. Mycorrhizal plants had a higher maximum uptake rate (Vmax) value than non-mycorrhizal plants, indicating that R. irregularis enhanced the NO3– uptake capacity of poplar. The expression of NRTs in roots, namely, NRT1;2, NRT2;4B, NRT2;4C, NRT3;1A, NRT3;1B, and NRT3;1C, was decreased by R. irregularis under conditions of 0 and 1 mM NH4NO3. This study demonstrated that the improved NO3– uptake capacity by R. irregularis was not achieved by up-regulating the expression of NRTs in roots. The mycorrhizal pathway might repress root direct pathway in the NO3– uptake by mycorrhizal plants.
miR-654-5p Targets HAX-1 to Regulate the Malignancy Behaviors of Colorectal Cancer Cells

Introduction. The biological roles of microRNA-654-5p (miR-654-5p) in cancers have been previously reported. However, its role in colorectal cancer (CRC) remains largely unknown. The purpose of this work was to investigate the roles and associated mechanisms in CRC. Methods Quantitative Real-Time PCR (qRT-PCR) was utilized to explore the expression pattern of miR-654-5p in CRC cells. Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and transwell invasion assay were conducted to investigate the effects of miR-654-5p on CRC cell proliferation, migration, and invasion, respectively. Moreover, the mechanisms behind miR-654-5p regulates CRC progression were investigated. Results Compared with normal cell line, miR-654-5p expression level was significantly suppressed in CRC cells. After overexpression of miR-654-5p, the malignancy behaviors of CRC cells including cell proliferation, migration, and invasion were remarkably decreased. Subsequently, we found hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) was a putative target for miR-654-5p. Rescue experiments showed overexpression of HAX-1 could partially reversed the effects of miR-654-4p on CRC cell events. Conclusion miR-654-5p was reduced expression in CRC cells and could regulate CRC progression via targeting HAX-1.
Demonstrating the Impact of Cognitive CEO on Firms’ Performance and CSR Activity

One aspect of entrepreneurship psychology also clarifies individual characteristics. Drawing from entrepreneurship psychology, the concept of a cognitive CEO has been formulated using the DAE statistical technique. The study elucidates that cognitive CEOs not only boost SME performance but also invigorate CSR activity. Data for listed SMEs for the years 2016–2018 are analyzed through the panel regression technique. Significantly, the study demonstrates that CEO age is positively interlinked with the growth and CSR activity of the firm. Moreover, the empirical underpinning of the results also reveals that state-owned enterprises and firms with high total assets prefer cognitive CEOs, who accelerate the firm’s value and invigorate CSR activity. The number of independent directors is analyzed as a moderator and is concluded to be an intensifier for both SME growth and CSR activity. Finally, 2SLS instrumental panel regression is used to validate the veracity of the empirical results.
Working Memory Predicts Hypothalamus-Pituitary-Adrenal Axis Response to Psychosocial Stress in Males

The hypothalamic-pituitary-adrenocortical (HPA) function is crucial for adaptation to stress and recovery of homeostasis. Physiological alteration in the HPA axis has been shown to play a pivotal role in the generation of stress-related disorders. A growing number of studies have begun to identify which variables are possible to predict individual HPA response and associated stress vulnerability. The current study investigated the relationship between working memory and the subsequent magnitude of HPA response to psychosocial stress in a non-clinical population. Working memory was assessed utilizing an n-back task (2/3-back) in thirty-nine healthy young men, whose electroencephalograms were recorded. The HPA response was measured using the percentage increase in cortisol to an acute psychosocial stress protocol called the Trier Social Stress Test (TSST). Our results show that longer reaction time and smaller amplitude of P2 predict a relatively lower HPA response to stress. Our study provides new insights into how neurocognitive factors can be used to predict HPA response to acute stress.
Time-of-Day-Dependent Physiological Responses to Meal and Exercise

The mammalian circadian clock drives the temporal coordination in cellular homeostasis and it leads the day-night fluctuation of physiological functions, such as sleep/wake cycle, hormonal secretion, and body temperature. The mammalian circadian clock system in the body is classified hierarchically into two classes, the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and the peripheral clocks in peripheral tissues such as the intestine and liver, as well as other brain areas outside the SCN. The circadian rhythm of various tissue-specific functions is mainly controlled by each peripheral clock and partially by the central clock as well. The digestive, absorptive, and metabolic capacities of nutrients also show the day-night variations in several peripheral tissues such as small intestine and liver. It is therefore indicated that the bioavailability or metabolic capacity of nutrients depends on the time of day. In fact, the postprandial response of blood triacylglycerol to a specific diet and glucose tolerance exhibit clear time-of-day effects. Meal frequency and distribution within a day are highly related to metabolic functions, and optimal time-restricted feeding has the potential to prevent several metabolic dysfunctions. In this review, we summarize the time-of-day-dependent postprandial response of macronutrients to each meal and the involvement of circadian clock system in the time-of-day effect. Furthermore, the chronic beneficial and adverse effects of meal time and eating pattern on metabolism and its related diseases are discussed. Finally, we discuss the timing-dependent effects of exercise on the day-night variation of exercise performance and therapeutic potential of time-controlled-exercise for promoting general health.
Effectiveness of AbobotulinumtoxinA in Post-stroke Upper Limb Spasticity in Relation to Timing of Treatment

Background: Recent studies of botulinum toxin for post-stroke spasticity indicate potential benefits of early treatment (i. e., first 6 months) in terms of developing hypertonicity, pain and passive function limitations. This non-interventional, longitudinal study aimed to assess the impact of disease duration on the effectiveness of abobotulinumtoxinA treatment for upper limb spasticity. Methods: The early-BIRD study (NCT01840475) was conducted between February 2013 and 2018 in 43 centers across Germany, France, Austria, Netherlands and Switzerland. Adult patients with post-stroke upper limb spasticity undergoing routine abobotulinumtoxinA treatment were followed for up to four treatment cycles. Patients were categorized by time from stroke event to first botulinum toxin-A treatment in the study (as defined by the 1st and 3rd quartiles time distribution) into early-, medium- and late- start groups. We hypothesized that the early-start group would show a larger benefit (decrease) as assessed by the modified Ashworth scale (MAS, primary endpoint) on elbow plus wrist flexors compared with the late-start group. Results: Of the 303 patients enrolled, 292 (96.4%) received ≥1 treatment and 186 (61.4%) received 4 injection cycles and completed the study. Patients in all groups showed a reduction in MAS scores from baseline over the consecutive injection visits (i.e., at end of each cycle). Although reductions in MAS scores descriptively favored the early treatment group, the difference compared to the late group did not reach statistical significance at the last study visit (ANCOVA: difference in adjusted means of 0.15, p = 0.546). Conclusions: In this observational, routine-practice study, patients in all groups displayed a benefit from abobotulinumtoxinA treatment, supporting the effectiveness of treatment for patients at various disease stages. Although the data revealed some trends in favor of early vs. late treatment, we did not find strong evidence for a significant benefit of early vs. late start of treatment in terms of reduction in MAS scores.
Serum Systemic Autoantibodies in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Objective: The aim of this retrospective study was to investigate the relationship between serum systemic autoantibodies and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Thirty-nine patients with anti-NMDAR encephalitis were examined for serum systemic autoantibodies (antinuclear antibodies, extractable nuclear antigen autoantibodies, rheumatoid factors, and anti-neutrophil cytoplasmic antibodies), in comparison with 39 neuromyelitis optica spectrum disorder (NMOSD) and 78 healthy controls. Clinical features, cerebrospinal fluid characteristics, and outcomes were compared between the two subgroups of anti-NMDAR patients with positive and negative systemic autoantibodies, respectively. Results: Anti-NMDAR encephalitis patients had higher frequency of positive serum systemic autoantibodies than healthy controls (23.1 vs. 2.6%, p = 0.001) and lower frequency than NMOSD (23.1 vs. 48.7%, p = 0.018). No patients were diagnosed comorbidities with non-organ-specific autoimmune diseases. Consciousness disturbance was more frequent in autoantibodies positive group than in the negative group (88.9 vs. 40.0%, p = 0.02). Autoantibody positive group had a poorer outcome than autoantibody negative group (55.6 vs. 86.7%, p = 0.043). There was a negative correlation between serum autoantibodies and outcomes in anti-NMDAR encephalitis patients (r = −0.325, p = 0.044). Conclusion: Our data demonstrated serum systemic autoantibodies were more frequent in anti-NMDAR encephalitis patients than in healthy controls and less frequent than NMOSD, which were associated with higher severity of disease.
Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study

Background: Cocaine is a psychostimulant drug used as performance enhancer throughout history. The prolonged use of cocaine is associated with addiction and a broad range of cognitive deficits. Currently, there are no medications proven to be effective for cocaine-use disorder (CocUD). Previous preliminary clinical work suggests some benefit from repetitive transcranial magnetic stimulation (rTMS) stimulating the prefrontal cortex (PFC), involved in inhibitory cognitive control, decision-making and attention. All published studies to date have been limited by small sample sizes and short follow-up times. Methods: This is a retrospective observational study of 284 outpatients (of whom 268 were men) meeting DSM-5 criteria for CocUD. At treatment entry, most were using cocaine every day or several times per week. All patients underwent 3 months of rTMS and were followed for up to 2 years, 8 months. Self-report, reports by family or significant others and regular urine screens were used to assess drug use. Results: Median time to the first lapse (resumption of cocaine use) since the beginning of treatment was 91 days. For most patients, TMS was re-administered weekly, then monthly, throughout follow-up. The decrease in frequency of rTMS sessions was not accompanied by an increase in lapses to cocaine use. Mean frequency of cocaine use was <1·0 day/month (median 0), while serious rTMS-related adverse events were infrequent, consistent with published reports from smaller studies. Conclusions: This is the first follow-up study to show that rTMS treatment is accompanied by long-lasting reductions in cocaine use in a large cohort.
Effects of Noise on the Behavioral and Neural Categorization of Speech

We investigated whether the categorical perception (CP) of speech might also provide a mechanism that aids its perception in noise. We varied signal-to-noise ratio (SNR) [clear, 0 dB, −5 dB] while listeners classified an acoustic-phonetic continuum (/u/ to /a/). Noise-related changes in behavioral categorization were only observed at the lowest SNR. Event-related brain potentials (ERPs) differentiated category vs. category-ambiguous speech by the P2 wave (~180–320 ms). Paralleling behavior, neural responses to speech with clear phonetic status (i.e., continuum endpoints) were robust to noise down to −5 dB SNR, whereas responses to ambiguous tokens declined with decreasing SNR. Results demonstrate that phonetic speech representations are more resistant to degradation than corresponding acoustic representations. Findings suggest the mere process of binning speech sounds into categories provides a robust mechanism to aid figure-ground speech perception by fortifying abstract categories from the acoustic signal and making the speech code more resistant to external interferences.
Survey of Blood Groups DEA 1, DEA 4, DEA 5, Dal, and Kai 1/Kai 2 in Different Canine Breeds From a Diagnostic Laboratory in Germany

More than twelve blood group systems have been described in dogs, but little is known about their distribution frequencies within breed populations. Here, we report on an extensive typing survey carried out using available reagents and either established or new clinical kits in purebred dogs from Germany. Leftover anticoagulated blood samples were examined using an immunochromatographic strip method for DEA 1, a gel column technique for Dal and Kai 1/2, and new card agglutination tests for DEA 4 and DEA 5 (which were partially compared with the gel column technique). Monoclonal antibodies were used for DEA 1 and Kai 1/2 typing, and polyclonal antibodies were used for all other types. Among the 206 dogs, 59.2% were DEA 1+, 100% DEA 4+, 9% (Card)/11% (Gel) DEA 5+, 89.3% Dal+, 96.6% Kai 1+, and 2.9% Kai 2+. None of the dogs were Kai 1+/2+, and only one was Kai 1–/2–. Dal– dogs were found in several breeds. Erythrocytes from most DEA 1+ dogs bound strongly on the strips. The agglutination reactions for DEA 5 on the new card tests were generally less than those on the gel column. The blood group pattern DEA 4+, DEA 5–, Dal+, Kai 1+/2– and either DEA 1+ or DEA 1– was found among 80% of the dogs. In this first extensive blood typing survey of purebred dogs from Europe, the proportions of positive and negative blood types were similar to those found in the United States and, for DEA 1, were also similar to those from other European countries, with considerable breed variation in blood types. The newer typing techniques seem to work well and will likely be useful for detecting and preventing specific blood type incompatibilities in the clinic.
Rheumatic diseases in China.

: Prevalence and clinical manifestations of 5 common rheumatic diseases in China are discussed. Systemic lupus erythematosus appears to be more prevalent in Chinese than in Caucasians with possibly different clinical manifestations, in particular less serositis. Rheumatoid arthritis may be less aggressive and seronegative arthridities are less common. Behcet's and aortitis are frequently seen but not temporal arteritis and polymyalgia rheumatica.