The recent Coronavirus Disease 2019 (COVID-19) pandemic has placed severe stress on healthcare systems worldwide, which is amplified by the critical shortage of COVID-19 tests.
In this study, we ...propose to generate a more accurate diagnosis model of COVID-19 based on patient symptoms and routine test results by applying machine learning to reanalyzing COVID-19 data from 151 published studies. We aim to investigate correlations between clinical variables, cluster COVID-19 patients into subtypes, and generate a computational classification model for discriminating between COVID-19 patients and influenza patients based on clinical variables alone.
We discovered several novel associations between clinical variables, including correlations between being male and having higher levels of serum lymphocytes and neutrophils. We found that COVID-19 patients could be clustered into subtypes based on serum levels of immune cells, gender, and reported symptoms. Finally, we trained an XGBoost model to achieve a sensitivity of 92.5% and a specificity of 97.9% in discriminating COVID-19 patients from influenza patients.
We demonstrated that computational methods trained on large clinical datasets could yield ever more accurate COVID-19 diagnostic models to mitigate the impact of lack of testing. We also presented previously unknown COVID-19 clinical variable correlations and clinical subgroups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Purpose
Although inhibition of renal sodium–glucose co‐transporter 2 (SGLT2) has a stable glucose‐lowering effect in patients with type 2 diabetes, the effect of SGLT2 inhibition on ...renal dysfunction in type 2 diabetes remains to be determined. To evaluate the renoprotective effect of SGLT2 inhibition more precisely, we compared the effects of tofogliflozin (a specific SGLT2 inhibitor) with those of losartan (an angiotensin II receptor antagonist) on renal function and beta‐cell function in db/db mice.
Experimental Approach
The effects of 8‐week tofogliflozin or losartan treatment on renal and beta‐cell function were investigated in db/db mice by quantitative image analysis of glomerular size, mesangial matrix expansion and islet beta‐cell mass. Blood glucose, glycated Hb and insulin levels, along with urinary albumin and creatinine were measured
Key Results
Tofogliflozin suppressed plasma glucose and glycated Hb and preserved pancreatic beta‐cell mass and plasma insulin levels. No improvement of glycaemic conditions or insulin level was observed with losartan treatment. Although the urinary albumin/creatinine ratio of untreated db/db mice gradually increased from baseline, tofogliflozin or losartan treatment prevented this increase (by 50–70%). Tofogliflozin, but not losartan, attenuated glomerular hypertrophy. Neither tofogliflozin nor losartan altered matrix expansion.
Conclusions and Implications
Long‐term inhibition of renal SGLT2 by tofogliflozin not only preserved pancreatic beta‐cell function, but also prevented kidney dysfunction in a mouse model of type 2 diabetes. These findings suggest that long‐term use of tofogliflozin in patients with type 2 diabetes may prevent progression of diabetic nephropathy.
Thermal and mechanical hypersensitivity in the injured region is a common complication. Although it is well known clinically that thermal and mechanical sensitivity of the oral mucosa is different ...from that of the skin, the mechanisms underlying injured pain of the oral mucosa remain poorly understood. The transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in primary afferent neurons are known to contribute to pathological pain. Therefore, we investigated whether TRPV1 and/or TRPA1 contribute to thermal and mechanical hypersensitivity following oral mucosa or whisker pad skin incision. Strong heat and mechanical and cold hypersensitivity was caused in the buccal mucosa and whisker pad skin following incisions. On day 3 after the incisions, the number of TRPV1-immunoreactive (IR) and TRPA1-IR trigeminal ganglion (TG) neurons innervating the buccal mucosa and whisker pad skin was significantly increased, and the number of TRPV1/TRPA1-IR TG neurons innervating whisker pad skin, but not the buccal mucosa, was significantly increased. Administration of the TRPV1 antagonist, SB366791, to the incised site produced a significant suppression of heat hyperalgesia in both the buccal mucosa and whisker pad skin, as well as mechanical allodynia in the whisker pad skin. Administration of the TRPA1 antagonist, HC-030031, to the incised site suppressed mechanical allodynia and cold hyperalgesia in both the buccal mucosa and whisker pad skin, as well as heat hyperalgesia in the whisker pad skin. These findings indicate that altered expressions of TRPV1 and TRPA1 in TG neurons are involved in thermal and mechanical hypersensitivity following the buccal mucosa and whisker pad skin incision. Moreover, diverse changes in the number of TRPV1 and TRPA1 coexpressed TG neurons in whisker pad skin-incised rats may contribute to the intracellular interactions of TRPV1 and TRPA1 associated with whisker pad skin incision, whereas TRPV1 and TRPA1 expression in individual TG neurons is involved in buccal mucosa–incised pain.
To elucidate if microglial P2Y12 receptor (P2Y12R) mechanisms are involved in the trigeminal spinal subnucleus caudalis (Vc; also known as the medullary dorsal horn) in intraoral cancer pain, we ...developed a rat model of tongue cancer pain. Squamous cell carcinoma (SCC) cells were inoculated into the tongue of rats; sham control rats received the vehicle instead. Nociceptive behavior was measured as the head-withdrawal reflex threshold (HWRT) to mechanical or heat stimulation applied to the tongue under light anesthesia. On day 14 after the SCC inoculation, activated microglia and P2Y12R expression were examined immunohistochemically in the Vc. The HWRT was also studied in SCC-inoculated rats with successive intra–cisterna magna (i.c.m.) administration of specific P2Y12R antagonist (MRS2395) or intraperitoneal administration of minocycline, a microglial activation inhibitor. Tongue cancer was histologically verified in SCC-inoculated rats, within which the HWRT to mechanical stimulation of the tongue was significantly decreased, as compared with that of vehicle-inoculated rats, although the HWRT to heat stimulation was not. Microglia was strongly activated on day 14, and the administration of MRS2395 or minocycline reversed associated nocifensive behavior and microglial activation in SCC-inoculated rats for 14 d. The activity of Vc wide dynamic range nociceptive neurons was also recorded electrophysiologically in SCC-inoculated and sham rats. Background activity and noxious mechanically evoked responses of wide dynamic range neurons were significantly increased in SCC-inoculated rats versus sham rats, and background activity and mechanically evoked responses were significantly suppressed following i.c.m. administration of MRS2395 in SCC-inoculated rats as compared with sham. The present findings suggest that SCC inoculation that produces tongue cancer results in strong activation of microglia via P2Y12 signaling in the Vc, in association with increased excitability of Vc nociceptive neurons, reflecting central sensitization and resulting in tongue mechanical allodynia.
The possibility of speech processing in the absence of an intelligible acoustic signal has given rise to the idea of a ‘
silent speech’ interface, to be used as an aid for the speech-handicapped, or ...as part of a communications system operating in silence-required or high-background-noise environments. The article first outlines the emergence of the silent speech interface from the fields of speech production, automatic speech processing, speech pathology research, and telecommunications privacy issues, and then follows with a presentation of demonstrator systems based on seven different types of technologies. A concluding section underlining some of the common challenges faced by silent speech interface researchers, and ideas for possible future directions, is also provided.
Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients ...with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1β (IL-1β) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar–innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)–labeled cells encircled by glial fibrillary acid protein–immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation (P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein–IR + IL-1β-IR cells, IL-1 type I receptor–IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation (P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation (P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1β mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.
The intestinal mucosa allows the residence of trillions of bacteria with which it interacts dynamically. To establish and maintain a mutually beneficial relationship, the mucosal immune system must ...enforce tolerance toward the vast non-pathogenic microbiota while simultaneously remaining reactive to potentially pathogenic microbes; the disruption of this delicate balance results in inflammatory bowel diseases. In this review, we describe advances in our understanding of regulatory mechanisms of the innate immune system and how these shape adaptive immune systems during steady-state and inflammatory processes in the intestinal mucosa.
Cancer stem cells (CSCs) have been shown as a distinct population of cancer cells strongly implicated with resistance to conventional chemotherapy. Metformin, the most widely prescribed drug for ...diabetes, was reported to target cancer stem cells in various cancers. In this study, we sought to determine the effects of metformin on head and neck squamous cell carcinoma (HNSCC). CSCs and non-stem HNSCC cells were treated with metformin and cisplatin alone, and in combination, and cell proliferation levels were measured through MTS assays. Next, potential targets of metformin were explored through computational small molecule binding analysis. In contrast to the reported effects of metformin on CSCs in other cancers, our data suggests that metformin protects HNSCC CSCs against cisplatin in vitro. Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG. On the other hand, we observed that metformin successfully decreased the proliferation of non-stem HNSCC cells. Computational drug⁻protein interaction analysis revealed mitochondrial complex III to be a likely target of metformin. Based on our results, we present the novel hypothesis that metformin targets complex III to reduce reactive oxygen species (ROS) levels, leading to the differential effects observed on non-stem cancer cells and CSCs.
Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection ...requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle’s energy as
244
±
29
stat
.
−
76
+
51
syst
.
exa–electron volts
(~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.
Editor’s summary
Cosmic rays are charged particles from space. At low energies, they mostly originate from the Sun, whereas at high energies, they are expected to be emitted by nearby active galaxies. The Telescope Array Collaboration now reports the detection of a cosmic ray event with an energy of about 240 exa–electron volts, more than a million times higher than that achieved by artificial particle accelerators. Such high-energy particles should experience only small deflections by foreground magnetic fields, but tracing back the arrival direction shows no obvious source galaxy. The authors suggest that the foreground magnetic fields might be stronger than expected, or there could be unknown particle physics at high energies. —Keith T. Smith
Detection of a highly energetic cosmic ray is traced back to its arrival direction, but no source galaxy is evident.
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