Evaluating Streptococcus mutans Colonization on 3D-Printed, Milled, and Conventional Acrylic Resin Materials: An In Vitro Study.

Purpose: To compare surface roughness and bacterial colonization of Streptococcus mutans to 3D printed (3DP), milled (M), and conventional (CV) acrylic resin. Methods: Thirty-six discs (n equals 12 per group) were fabricated from 3DP, M, and CV materials. One surface of sample was polished (Po); the opposite surface was left unpolished (UPo). Surface roughness (µm) was assessed using a contact profilometer. The specimens were placed in S. mutans suspension and incubated at 37 degrees Celsius overnight. The attached colonies were separated using a sonicator, and the resulting solution was diluted to 10-3 to assess colony-forming units per milliliter (CFU/ml) after 48 hours. The colonies were categorized into a quantitative S. mutans (QS) index. Data were analyzed using one-way ANOVA, chi-squares, and multivariate analysis of variance analysis with the least significant difference (LSD) post-hoc test (P<0.05). Results: Roughness average (Ra) values of CV were higher than 3DP and M for UPo surfaces (P<0.001; 3DP=0.10; M=0.13; CV=0.26 µm, respectively). For Po and UPo surfaces, the CV harbored more S. mutans colonies than M and 3DP (P<0.001; 3DP=5.2x10 6 ; M=4.7x10 6 ; CV=1.49x10 7 CFU/ml, respectively). M group had the lowest range of QS scores, while CV had the highest range (P<0.001). Conclusions: Digitally manufactured material provides smoother surfaces than the conventional group, resulting in fewer Streptococcus mutans colonies. However, all the material groups must still be adequately polished to prevent the colonization of S. mutans, regardless of the manufacturing methods, as higher S. mutans counts were observed with an increase in surface roughness values.

Significance of Cuproptosis-related genes in immunological characterization, diagnosis and clusters classification in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological disorder that affects millions of people throughout the world. Cuproptosis is a newly discovered form of programmed cell death linked to several neurological disorders. Nevertheless, the precise mechanisms of Cuproptosis-related genes (CRGs) in PD remain unknown. This study investigated immune infiltration and CRG expression profiling in patients with Parkinson's disease and healthy controls. Subsequently, we construct a predictive model based on 5 significant CRGs. The performance of the predictive model was validated by nomograms and external datasets. Additionally, we classified PD patients into two clusters based on CRGs and three gene clusters based on differentially expressed genes (DEG) of CRGs clusters. We further evaluated immunological characterization between the different clusters and created the CRGs scores to quantify CRGs patterns. Finally, we investigate the prediction of CRGs drugs and the ceRNA network, providing new insights into the pathogenesis and management of PD.

Sex Difference in the Association between Depression and Adherence to Recommended Dilated Eye Examinations among Patients with Diabetes: Findings from National Health and Nutrition Examination Survey.

INTRODUCTION: The relationship between depression and adherence to regular dilated fundus examination (DFE) in patients with diabetes remains unclear. This study aimed to assess the association between depression and adherence to annual or biennial DFE among individuals with diabetes. METHODS: In this cross-sectional study, we used the National Health and Nutrition Examination Survey database from 2005 to 2016 which contains information on demographics, clinical characteristics, health-related factors, and the time since last DFE. Participants were classified as having depression based on a score of >9 on the Patient Health Questionnaire-9. The main outcomes were the association between depression and the adherence of patients with diabetes to annual or biennial DFE. The second objective was to explore the potential influence of gender in this association. The independent association of depression with DFE compliance was explored by a series of multivariate logistic regression analyses (overall sample and then stratified by sex). RESULTS: In total, 3,656 eligible participants were identified. The adherence rates to annual or biennial DFE were all higher for participants without depression than those with depression (64.8% vs. 56.1% and 80.3% vs. 69.7%, respectively). In the multivariate analyses, depression was neither independently associated with the adherence to annual DFE nor biennial DFE in the overall sample. An interaction was observed between depression and gender for the adherence to annual or biennial DFE (p = 0.017 and p = 0.026, respectively). When analyses were stratified by sex, female patients with diabetes and depression had a significantly increased odds ratio (OR) of being nonadherent to annual and biennial DFE (OR = 1.52, 95% confidence interval [CI]: 1.02-2.25, p = 0.039; OR = 1.55, 95% CI: 1.02-2.35, p = 0.039, respectively). However, this relationship was not evident in men with diabetes. CONCLUSIONS: The independent association between depression and DFE compliance varied by sex, that is, only female patients with diabetes and depression were at a higher risk of nonadherence to annual or biennial DFE compared to those without depression.

Chronic cough relief by allosteric modulation of P2X3 without taste disturbance.

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.

Mechanotransduction governs CD40 function and underlies X-linked Hyper IgM syndrome.

B cell maturation in germinal centers (GCs) depends on cognate interactions between the T and B cells. Upon interaction with CD40 ligand (CD40L) on T cells, CD40 delivers co-stimulatory signals alongside B cell antigen receptor (BCR) signaling to regulate affinity maturation and antibody class-switch during GC reaction. Mutations in CD40L disrupt interactions with CD40, which lead to abnormal antibody responses in immune deficiencies known as X-linked Hyper IgM syndrome (X-HIgM). Assuming that physical interactions between highly mobile T and B cells generate mechanical forces on CD40-CD40L bonds, we set out to study the B cell mechanobiology mediated by CD40-CD40L interaction. Using a suite of biophysical assays we find that CD40 forms catch bond with CD40L where the bond lasts longer at larger forces, B cells exert tension on CD40-CD40L bonds, and force enhances CD40 signaling and antibody class-switch. Significantly, X-HIgM CD40L mutations impair catch bond formation, suppress endogenous tension, and reduce force-enhanced CD40 signaling, leading to deficiencies in antibody class switch. Our findings highlight the critical role of mechanotransduction in CD40 function and provide insights into the molecular mechanisms underlying X-HIgM syndrome.

A review of studies on gut microbiota and levodopa metabolism.

Parkinson's disease (PD) is the second most common neurodegenerative disease globally. Levodopa (L-dopa) has been the cornerstone for treating Parkinson's since the 1960s. However, complications such as "wearing-off" and dyskinesia inevitably appear with disease progression. With the further development of microbiomics in recent years, It has been recognized that gut microbiota plays a crucial role in Parkinson's disease pathogenesis. However, Little is known about the impact of gut microbiota in PD treatment, especially in levodopa metabolism. This review examines the possible mechanisms of gut microbiota, such as Helicobacter pylori, Enterobacter faecalis, and Clostridium sporogenes, affecting L-dopa absorption. Furthermore, we review the current status of gut microbiota intervention strategies, providing new insights into the treatment of PD.

Epigenetically modified AP-2α by DNA methyltransferase facilitates glioma immune evasion by upregulating PD-L1 expression.

Programmed death-ligand 1 (PD-L1) ensures that tumor cells escape T-cell-mediated tumor immune surveillance. However, gliomas are characteristic of the low immune response and high-resistance therapy, it is necessary to understand molecular regulatory mechanisms in glioblastoma, especially the limited regulation of PD-L1 expression. Herein, we show that low expression of AP-2α is correlated with high expression of PD-L1 in high-grade glioma tissues. AP-2α binds directly to the promoter of the CD274 gene, not only inhibits the transcriptional activity of PD-L1 but enhances endocytosis and degradation of PD-L1 proteins. Overexpression of AP-2α in gliomas enhances CD8+ T cell-mediated proliferation, effector cytokine secretion, and cytotoxicity in vitro. Tfap2a could increase the cytotoxic effect of Cd8+ T cells in CT26, B16F10, and GL261 tumor-immune models, improve anti-tumor immunity, and promote the efficacy of anti-PD-1 therapy. Finally, the EZH2/H3K27Me3/DNMT1 complex mediates the methylation modification of AP-2α gene and maintains low expression of AP-2α in gliomas. 5-Aza-dC (Decitabine) treatment combines with anti-PD-1 immunotherapy to efficiently suppress the progression of GL261 gliomas. Overall, these data support a mechanism of epigenetic modification of AP-2α that contributes to tumor immune evasion, and reactivation of AP-2α synergizes with anti-PD-1 antibodies to increase antitumor efficacy, which may be a broadly applicable strategy in solid tumors.

Treatment of Early Undifferentiated Chronic Monoarthritis of the Wrist by Arthroscopic Wrist Synovectomy Combined with Partial Denervation.

OBJECTIVE: Undifferentiated chronic monosecarthritis (UCMA) is a group of inflammatory joint diseases that has the potential to progress to other diseases and can seriously affect patients' quality of life. There is yet no unified consensus regarding treatment of UCMA. This study aimed to investigate the efficacy of arthroscopic synovectomy combined with partial wrist denervation in treating Larsen 1-3 UCMA. METHODS: In this case series, we reviewed 14 patients with UCMA treated by arthroscopic synovectomy combined with partial denervation from February 2017 to June 2020. The mean duration of symptoms was 17.4 months (range, 4-60 months), and the mean follow-up was 13.3 months (range, 6-23 months). The anterior and posterior interosseous nerves were severed at the distal forearm, and the radiocarpal, midcarpal, and distal radial ulnar joint synovial membranes were arthroscopically resected at the wrist. The clinical evaluation indices included the visual analogue scale score (VAS) for pain, grip strength, range of (active) motion of the wrist, total active motion, and Mayo wrist score. Larsen's scoring method was used as the imaging evaluation index. RESULTS: At the last follow-up, significant clinical improvements were observed in the visual analogue scale (VAS) score for pain (6.0 (5.0-6.3) vs 1.0 (1.0-2.3), P = 0.001) and Mayo wrist score (42.1 ± 9.7 vs 61.8 ± 12.3, P < 0.0001). No significant changes were found in grip strength (15.9 ± 4.5 vs 16.6 ± 4.7, P = 0.230) or the flexion-extension arc (58.9 ± 39.0 vs 64.3 ± 36.5, P = 0.317), although the mean and median did show positive changes. Among the three patients who showed progress in imaging, there was no significant difference in their pain and functional scores compared to those who did not progress. One patient underwent total wrist fusion 17 months after the operation. CONCLUSION: Arthroscopic wrist synovectomy combined with partial wrist denervation can provide sustained pain relief and functional recovery for patients with Larsen 1-3 UCMA.

Neuroinflammation and peripheral immunity: Focus on ischemic stroke.

Ischemic stroke (IS) produces a powerful inflammatory cascade in the brain, resulting in the occurrence of neuroinflammation. Neuroinflammation is triggered not only by resident immune cells, but also by neutrophils, macrophages, and T lymphocytes infiltrating the peripheral immune system. The disruption of the blood-brain barrier appears to exacerbate inflammatory infiltrates after IS. In turn, IS also has effects on peripheral immunity, manifested as peripheral immunosuppression syndrome, which increases the risk of stroke-associated infections such as pneumonia. Moreover, strokes also damage peripheral organs such as the heart, lungs, spleen, and kidneys. The purpose of this review is to provide an overview of central neuroinflammation and stroke-induced immunosuppression in the context of IS.

Stem-cell based soft tissue substitutes: Engineering of crosslinked polylysine-hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis.

BACKGROUND: The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. METHODS: The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. RESULTS: The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the green fluorescent protein-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared with the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. CONCLUSIONS: The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future.

Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids.

Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naïve B cells to induce the formation of germinal centers (GC), a subanatomical microenvironment that converts naïve B cells into antibody-secreting plasma cells. Using a three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate that conjugates triggered robust expression of hallmark GC markers, B cell receptor clustering, intracellular signaling, and somatic hypermutation. These responses depended on the relative immunogenicity of the conjugate and correlated with the humoral response in vivo. The occurrence of these mechanisms was exploited for the discovery of high-affinity antibodies against components of the conjugate on a time scale that was significantly shorter than for typical animal immunization-based workflows. Collectively, these findings highlight the potential of synthetic organoids for rapidly predicting conjugate vaccine efficacy as well as expediting antigen-specific antibody discovery.

Safety and dose escalation of the targeted oncolytic adenovirus OBP-301 for refractory advanced liver cancer: Phase I clinical trial.

OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 × 1012 viral particles. The most common treatment-emergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.

Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas.

Activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCLs) are characterized by constitutive activation of nuclear factor κB driven by the B-cell receptor (BCR) and Toll-like receptor (TLR) pathways. However, BCR-pathway-targeted therapies have limited impact on DLBCLs. Here we used >1,100 DLBCL patient samples to determine immune and extracellular matrix cues in the lymphoid tumour microenvironment (Ly-TME) and built representative synthetic-hydrogel-based B-cell-lymphoma organoids accordingly. We demonstrate that Ly-TME cellular and biophysical factors amplify the BCR-MYD88-TLR9 multiprotein supercomplex and induce cooperative signalling pathways in ABC-DLBCL cells, which reduce the efficacy of compounds targeting the BCR pathway members Bruton tyrosine kinase and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). Combinatorial inhibition of multiple aberrant signalling pathways induced higher antitumour efficacy in lymphoid organoids and implanted ABC-DLBCL patient tumours in vivo. Our studies define the complex crosstalk between malignant ABC-DLBCL cells and Ly-TME, and provide rational combinatorial therapies that rescue Ly-TME-mediated attenuation of treatment response to MALT1 inhibitors.

Research on Diagnostic Markers for Post-Stroke Cognitive Impairment.

Objective: Post-stroke cognitive impairment (PSCI) is secondary to stroke, and is a significant burden for patients, their families and society as a whole. Our study aimed to investigate the predictive value of ß-amyloid 42 (Aß42) and hemoglobin (Hb) in the diagnosis of PSCI. Methods: 120 patients were selected and then assigned to either the PSCI group, Alzheimer's disease (AD) group or post-stroke cognitive normal (PSCN) group. Baseline data were recorded. Correlation between Aß42 and Hb and cognitive scores was evaluated. Then, the ability of these indicators to predict PSCI was compared based on logistic regression analysis and ROC curve. Results: Aß42 and Hb in the PSCI group were lower than in the AD and PSCN groups (P < .05). Compared with AD, hypertension (HTN) and Hb were independent risk factors for PSCI (P < .05), and Aß42 was a relevant risk factor for PSCI (P = .063). Compared with PSCN, age and Hb posed a threat to the occurrence of PSCI (P < .05). Under the ROC curve, the area under the curve (AUC) of the joint diagnosis of Aß42 and Hb was 0.7169, specificity was 0.625 and sensitivity reached 0.800. Conclusion: Aß42 and Hb in patients with PSCI were significantly lower than in the AD and PSCN groups, and were risk factors for PSCI. When the two are combined, the differential diagnosis performance may be improved.

Synergistic efficacy of telomerase-specific oncolytic adenoviral therapy and histone deacetylase inhibition in human hepatocellular carcinoma.

The telomerase-specific oncolytic adenovirus Telomelysin and the histone deacetylase inhibitor AR42 have demonstrated anticancer effects in preclinical models of human hepatocellular carcinoma (HCC). However, the clinical development of Telomelysin may be hindered by human antiviral immunity and tumor resistance. Combining oncolytic and epigenetic therapies is a viable approach for treating various cancers. This study investigated the potential synergism of Telomelysin and AR42 and the relevant underlying mechanisms. Telomelysin and AR42 exhibited synergistic antiproliferative effects in human HCC models in vitro and in vivo. Apoptosis induced by Telomelysin was significantly enhanced by AR42 in both PLC5 and Hep3B HCC cells. AR42 treatment unexpectedly attenuated the expression of the coxsackievirus and adenovirus receptor and the mRNA levels of human telomerase reverse transcriptase, which may be positively associated with the cytotoxicity of Telomelysin. Meanwhile, the cellular antiviral interferon response was not altered by AR42 treatment. Further, we found that Telomelysin enhanced Akt phosphorylation in HCC cells. AR42 reduced Telomelysin-induced phospho-Akt activation and enhanced Telomelysin-induced apoptosis. The correlation of Akt phosphorylation with drug-induced apoptosis was validated in HCC cells with upregulated or downregulated Akt signaling. Combination therapy with Telomelysin and AR42 demonstrated synergistic anti-HCC efficacy. Clinical trials investigating this new combination regimen are warranted.

Sarcopenia and myosteatosis are associated with survival in patients receiving immunotherapy for advanced hepatocellular carcinoma.

OBJECTIVES: To investigate the association of sarcopenia, myosteatosis, and sarcopenic obesity with survival outcomes among patients who underwent immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective analysis, patients who initiated immunotherapy for advanced HCC were enrolled. Sarcopenia and myosteatosis were evaluated on pretreatment CT at L3 level by skeletal muscle index and mean muscle attenuation using predefined cutoff values. Sarcopenic obesity was defined as concurrent sarcopenia and body mass index > 25 kg/m2. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 138 patients was included (discovery cohort n = 111, validation cohort n = 27). In the discovery cohort, patients with sarcopenia exhibited significantly poorer PFS (p = 0.048) and OS (p = 0.002) than patients without sarcopenia. Patients with myosteatosis exhibited significantly poorer PFS (p < 0.001) and OS (p < 0.001) than patients without myosteatosis. Patients with sarcopenic obesity compared to patients without sarcopenic obesity exhibited significantly poorer OS (p = 0.006) but not PFS (p = 0.31). In multivariate analysis adjusting for patient demographics, tumor extent, and liver function reserve, myosteatosis remained an independent predictor of poor PFS (p = 0.014) and OS (p = 0.007); sarcopenia remained an independent predictor for poor OS (p = 0.007). The prediction models for survival outcomes built by the discovery cohort showed similar performance in the validation cohort. CONCLUSIONS: Sarcopenia and myosteatosis are independent prognostic factors in patients who received immunotherapy for advanced HCC. KEY POINTS: • Sarcopenia and myosteatosis can be evaluated by CT at L3 level. • Sarcopenia, myosteatosis, and sarcopenic obesity were associated with poor survival outcomes in patients who underwent immunotherapy for advanced HCC. • Myosteatosis was an independent predictor of PFS and OS, and sarcopenia was independent for OS in these patients.

Evaluation of microbial air quality and aerosol distribution in a large dental clinic.

PURPOSE: To evaluate the microbial air quality during dental clinical procedures in a large clinical setting with increasing patient capacity. METHODS: This was a single-center, observational study design evaluating the microbial air quality and aerosol distribution during normal clinical sessions at 5% (sessions 1 and 2) and at > 50% (session 3) treatment capacity of dental aerosol generating procedures. Sessions 1 and 2 were evaluated on the same day with a 30-minute fallow time between the sessions. Session 3 was evaluated on a separate day. For each session, passive air-sampling technique was performed for three collection periods: baseline, treatment, and post-treatment. Blood agar plates were collected and incubated at 37°C for 48 hours. Colonies were counted using an automatic colony counter. Mean colony forming units (CFU) per plate were converted to CFU/m²/h. RESULTS: Kruskal Wallis test was performed to compare the mean CFU/m²/h between the clinic sessions. Statistically significant differences were observed between sessions 1 and 2 (P< 0.05), but not between sessions 2 and 3 (P> 0.05). Combining all clinical sessions, the mean CFU/m²/h were 977 (baseline), 873 (treatment), and 1,631 (post-treatment) for the collection periods. A decrease-to-increase CFU/m²/h trend was observed from baseline to treatment, and from treatment to post-treatment that was observed for all clinic sessions and was irrespective to treatment capacity. Higher amounts of CFU/m²/h were found near the air exhaust outlets for all three clinic sessions. Microbial aerosol distribution is most likely due to the positions and power levels of the air inlets and outlets, and to a lesser extent with patient treatment capacity. CLINICAL SIGNIFICANCE: Dental clinics should be designed and optimized to minimize the risk of airborne transmissions. The results of this study emphasize the need to evaluate dental clinic ventilation systems.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

A prospective trial to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with arsenic trioxide and carboplatin in locally advanced cervical cancer: a study protocol for randomized controlled clinical.

BACKGROUND: Cervical cancer is the fourth most common malignancy in women, which is threatening female reproductive tract health. Chemotherapy can be used for neoadjuvant therapy of locally advanced cervical cancer and postoperative adjuvant therapy for patients with high-risk factors, so as to reduce the focus, sensitize radiotherapy, and reduce recurrence. The current first-line treatment is paclitaxel combined with platinum. Many literature studies have found that As2O3 alone or in combination with platinum drugs have good efficacy in a variety of tumors both in vivo and in vitro. Moreover, our research group has verified that the efficacy of As2O3 combined with platinum drugs in the treatment of cervical cancer is not inferior to the traditional first-line regimen at the cellular and animal levels, and paclitaxel is more expensive than As2O3. Hence, we aim to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. METHODS: Sixty participants in the IB2, IIA2, and IIB stages of cervical cancer will be recruited in this study. After excluding patients who did not meet the criteria, they were randomly assigned to two groups in a 1:1 ratio. All patients underwent colposcopic biopsies to confirm the diagnosis and detailed clinical examinations. Eligible patients will receive either 2 cycles of paclitaxel and carboplatin or As2O3 and carboplatin every 3 weeks. Patients were assessed for clinical efficacy after the second cycle of chemotherapy. Patients who had disease stable or disease progression at these time points will receive concurrent chemotherapy and radiation directly, while responders will receive PiverRutledge grade III radical hysterectomy and bilateral pelvic lymphadenectomy. Both groups of patients undergoing radical hysterectomy were given adjuvant therapy as per protocol-defined criteria. The efficacy and toxicity of the two groups were evaluated according to WHO acute and subacute toxicity classification standards. DISCUSSION: This is the first single-center, prospective, two-arm design, open-label randomized control trial that will evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. TRIAL REGISTRATION: ChineseClinicalTrialRegistry ChiCTR1900023822 . Registered on 13 June 2019.