Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

Unveiling disparities: examining differential item functioning's impact on racial health equity among white and black populations.

OBJECTIVES: This paper aims to examine the psychometric properties of social capital indicators, comparing Black and White respondents to identify the extent of measurement invariance in social capital by race. STUDY DESIGN: We used data from the longitudinal study Midlife in the United States (MIDUS), waves 1 through 3 (1995-2016). METHODS: Data were from 6513 respondents (5604 White and 909 Black respondents). Social capital indicators were social cohesion, contributions to community, and community involvement. We used Structural Equation Modeling and Item Response Theory methods to test for measurement invariance in social capital by race. RESULTS: We observed violations of longitudinal and multi-group measurement invariance (MI) at configural and metric levels on two scales. Factor structures and indicator loadings were inconsistent over time. In IRT analysis, 'Many people come for advice' exhibited Differential Item Functioning (DIF), indicating a consistent advantage for White respondents on the contributions to community scale. Despite similar social capital levels (P(χ2,2) = 0.00), DIF was found in all contributions to community items and some community involvement items when examining race and education interaction. CONCLUSIONS: Invariance issues in social capital items suggest potential biases in comparing Black and White respondents. Recognizing these biases is essential. Future social capital research should assess existing data assumptions and involve stakeholders from diverse communities in creating new items.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[The relationship between differentially expressed thyroid cancer genes and clinical characteristics in metastatic children and adolescents].

Objective: To investigate the relationship between genes and clinical characteristics in children and adolescents with metastatic differentiated thyroid cancer (caDTC). Methods: A cross sectional study. A total of 67 caDTC patients with lymph node metastasis or distant metastasis in Peking Union Medical College Hospital from December 2020 to December 2022 were included, according to the inclusion and exclusion criteria. Then the differences in clinicopathologic features and iodine intake were compared among different genomes, and the age subgroups divided by the age of 12 were further analyzed. Results: Among the 67 cases of caDTC, the diagnosed age [M(Q1, Q3)]was 13.2 (9.7, 16.9) years old, with 23 males and 44 females. There were 68.7% (46/67) of patients have distant metastasis (M1 stage). Pathogenic or potentially pathogenic gene variants were detected in 68.7% (46/67) of the patients, with RET or NTRK fusion (RET/NTRK) being the most common [43.3%(29/67)], BRAF V600E mutation followed [19.4%(13/67)].There was only 1 caDTC with NRAS Q61R mutation. The patients were divided into RET/NTRK fusion group (n=29), BRAF mutation group (n=12), other mutation group (n=4), and non-mutation group (n=21) (1 patient was not included in the gene mutation subgroup comparison due to the presence of NRAS Q61R mutation and BRAF V600E mutation). The comparison of gene feature groups showed that compared to the BRAF mutation group, caDTC with RET/NTRK fusion tended to have a lower age at diagnosis [12.6(9.3, 15.9) vs 17.2(15.5, 18.1) years old, P<0.001], the proportion of mutation load≥2 was higher (10.4% vs 8.3%, P=0.027), with statistically significant difference. Among 46 M1 stage patients, 71.7% (33/46) had initial iodine intake, and 30.4% (14/46) developed radioiodine-refractory (RAIR). In age group comparison, the<12 year old group had a higher proportion of male patients (51.9% vs 22.5%, P=0.013) and a lower incidence of BRAF V600E mutations (0 vs 32.5%, P<0.001) compared to the≥12 year old group, and the differences were statistically significant. Conclusions: The incidence of RET/NTRK fusion ranks first in metastatic caDTC, featured with younger age at diagnosis and higher rate of distant metastasis. Although most metastatic lesions initially consume iodine, they are prone to RAIR. Attention should be paid to the potential role of RET/NTRK fusion in the invasion and iodine resistance of young caDTC patients.

[Clinical characteristics and associated factors of mild cognitive impairment in patients with common cardiovascular diseases].

Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014ï¼½, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.

[Transscleral ciliary surgery in glaucoma:from destructive surgery to minimally invasive surgery].

Over the years, there has been significant advancement in the safety and effectiveness of external cyclosurgery for glaucoma. This progress ranges from the initial "cyclodestructive surgery" to modern cycloplasty techniques, expanding beyond end-stage glaucoma treatment. Notably, innovative approaches like micropulse transscleral cycloplasty and ultrasonic cycloplasty are now being employed in earlier stages of glaucoma with better visual acuity, qualifying as minimally invasive procedures. Through a comprehensive review of the historical evolution of external cyclosurgery, elucidation of the mechanisms, clinical outcomes, and potential complications associated with novel cycloplasty techniques, and integration of practical clinical insights, this article aims to furnish clinicians with a profound comprehension of external cyclosurgery for glaucoma.

Compressibility and Structural Transformations of Aluminogermanate Imogolite Nanotubes under Hydrostatic Pressure.

We present in situ pressure experiments on aluminogermanate nanotubes studied by X-ray scattering and absorption spectroscopy measurements. Structural transformations under hydrostatic pressure below 10 GPa are investigated as a function of the morphology, organization, or functionalization of the nanotubes. Radial deformations, ovalization for isolated nanotubes, and hexagonalization when they are bundled are evidenced. Radial collapse of single-walled nanotubes is shown to occur, in contrast to the double-walled nanotubes. The effect of the transmitting pressure medium used on the collapse onset pressure value is demonstrated. Axial Young's moduli are determined for isolated (400 GPa) and bundled (600 GPa) single-walled nanotubes, double-walled nanotubes (440 GPa), and methylated single-walled nanotubes (200 GPa).

Comparison of His-Purkinje Conduction System Pacing with Atrial-Ventricular Node Ablation and Pharmacotherapy in HFpEF Patients with Recurrent Persistent Atrial Fibrillation (HPP-AF study).

BACKGROUND: There is currently no particularly effective strategy for patients with persistent atrial fibrillation accompanying heart failure with preserved ejection fraction (HFpEF), especially with recurrent atrial fibrillation after ablation. In this study, we will evaluate a new treatment strategy for patients with persistent atrial fibrillation who had at least two attempts (≧2 times) of radio-frequency catheter ablation but experienced recurrence, and physiologic conduction was reconstructed after atrioventricular node ablation or drug therapy, to control the patient's ventricular rate to maintain a regular heart rhythm, which is called His-Purkinje conduction system pacing (HPCSP) with atrioventricular node ablation. METHODS AND RESULTS: This investigator-initiated, multicenter prospective randomized controlled trial aimed to recruit 296 randomized HFpEF patients with recurrent atrial fibrillation. All the enrolled patients were randomly assigned to the pacing group or the drug treatment group. The primary endpoint is differences in cardiovascular events and clinical composite endpoints (all-cause mortality) between patients in the HPCSP and drug-treated groups. Secondary endpoints included heart failure hospitalization, exercise capacity assessed by cardiopulmonary exercise tests, quality of life, echocardiogram parameters, 6-minute walk distance, NT-ProBNP, daily patient activity levels, and heart failure management report recorded by the CIED. It is planned to compete recruitment by the end of 2023 and report in 2025. CONCLUSIONS: The study aims to determine whether His-Purkinje conduction system pacing with atrioventricular node ablation can better improve patients' symptoms and quality of life, postpone the progression of heart failure, and reduce the rate of rehospitalization and mortality of patients with heart failure. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1900027723, URL: http://www.chictr.org.cn/edit.aspx?pid=46128&htm=4.

[Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy].

Temozolomide resistance is a major cause of recurrence and poor prognosis in neuroglioma. Recently, growing evidence has suggested that mitophagy is involved in drug resistance in various tumor types. However, the role and molecular mechanisms of mitophagy in temozolomide resistance in glioma remain unclear. In this study, mitophagy levels in temozolomide-resistant and -sensitive cell lines were evaluated. The mechanisms underlying the regulation of mitophagy were explored through RNA sequencing, and the roles of differentially expressed genes in mitophagy and temozolomide resistance were investigated. We found that mitophagy promotes temozolomide resistance in glioma. Specifically, small ubiquitin-like modifier specific protease 6 (SENP6) promoted temozolomide resistance in glioma by inducing mitophagy. Protein-protein interactions between SENP6 and the mitophagy executive protein PTEN-induced kinase 1 (PINK1) resulted in a reduction in small ubiquitin-like modifier 2 (SUMO2)ylation of PINK1, thereby enhancing mitophagy. Our study demonstrates that by inducing mitophagy, the interaction of SENP6 with PINK1 promotes temozolomide resistance in glioblastoma. Therefore, targeting SENP6 or directly regulating mitophagy could be a potential and novel therapeutic target for reversing temozolomide resistance in glioma.

[Percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of spinal metastases].

OBJECTIVE: To investigate the effectiveness of percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of patients with spinal metastases. METHODS: In the study, 12 patients of spinal metastases treated with percutaneous pedicle screw fixation combined expandable tubular retractor in our hospital were retrospectively reviewed between June 2017 and October 2019. Among the 12 patients, 9 were males and 3 were females; the median age was 62.5 years [(65.1±2.9) years]. The decompression segment of 7 patients was located at the lower thoracic spine (including 1 patient with incomplete paraplegia) and the decompression segment of 5 patients was located at the lumbar spine; Tomita score was 6.0±0.6. Perioperative data of the patients were reviewed. Visual analog scale (VAS score), Karnofsky score, and Eastern Cooperative Oncology Group (ECOG) score were compared before and after surgery. The patient's survival, adjuvant treatment, and internal fixation failure were observed in the follow-up period. RESULTS: All the 12 patients had a successful operation with percuta-neous pedicle screw fixation combined expandable tubular retractor. The average operative time, blood loss, and blood transfused of the patients were (247.0±14.6) min, (804.2±222.3) mL and (500.0±100.0) mL, respectively. The average amount of drainage was (240.8±79.3) mL. Drainage tubes were pulled out early postoperative [(3.2±0.3) d], allowing early mobilization. The patients discharged (7.8±0.8) d postoperative. All the patients were followed up for 6-30 months, and the average overall survival time was (13.6±2.4) months. During the follow-up period, 2 patients experienced screw displacement, the internal fixation was stable after conservative treatment and no revision surgery was performed. The VAS of the patients was 7.1±0.2 before surgery, which decreased to 2.3±0.1 and 2.8±0.4 at 3 and 6 months after surgery (P < 0.05). The Karnofsky score of the patients was 59.2±1.9 before surgery, which increased to 75.0±1.9 and 74.2±3.1 at 3 and 6 months after surgery (P < 0.05). The ECOG of the patients was 2.3±0.2 before surgery, which decreased to 1.7±0.1 and 1.7±0.2 at 3 and 6 months after surgery (P < 0.05). CONCLUSION: For selected patients with spinal metastases, minimally invasive surgical treatment of spinal metastases (percutaneous pedicle screw internal fixation combined with expandable tubular retractor) can effectively relieve the clinical symptoms and improve the quality of life, with satisfactory clinical outcome.

[Effect of pelvic peritoneum reconstruction on the prognosis of patients underwent laparoscopic low anterior resection of rectal adenocarcinoma].

Objective: To investigate the effect of pelvic peritoneum reconstruction on the prognosis of patients underwent laparoscopic low anterior resection of rectal adenocarcinoma. Methods: This retrospective cohort study included 97 patients who underwent laparoscopic low anterior resection of rectal adenocarcinoma in General Surgery Department, the First Affiliated Hospital of Soochow University from January 2017 to June 2021. According to the implementation of pelvic peritoneum reconstruction, the subjects were divided into study group (48 patients underwent pelvic peritoneum reconstruction after laparoscopic resection) and control group (49 patients not underwent pelvic peritoneum reconstruction). The two groups were compared in terms of Wexner score of anal function, anorectal manometry results, normal rate of defecation sensation, pelvic floor anatomical structure and postoperative complications. Five-year survival analysis was performed. Results: Patients in the study group and the control group were (61.25±10.38) years old and (59.47±11.40) years old (P>0.05). The proportions of male patients were 60.4% (29 cases) and 55.1% (27 cases) (P>0.05) in the study group and control group, respectively. At 3, 6 and 12 months after surgery, Wexner scores of anal function in the study group were lower than those in the control group [(14.29±2.07) vs (16.33±2.18), P<0.001; (9.57±2.34) vs (11.26±2.85), P=0.002; (5.41±1.36) vs (7.86±1.95), P<0.001, respectively]. The anal resting pressure and anal systolic pressure of the study group were higher than those of the control group [(56.29±7.31) mmHg vs (52.88±6.65) mmHg, P=0.018; (129.33±17.36) mmHg vs (110.45±15.22) mmHg, P<0.001, respectively] (1 mmHg=0.133 kPa). The rectal sensory volume, rectal maximum tolerance volume, and the length of anal high-pressure area in the study group were greater than those in the control group [(32.15±4.38) vs (29.76±4.29), P=0.008; (209.57±40.27) vs (184.39±37.56), P=0.002; (3.07±0.52) vs (2.80±0.49), P=0.010, respectively]. At 3 and 6 months after surgery, the normal rates of defecation sensation in the study group were 47.9% (23 cases) and 70.8% (34 cases), respectively, higher than those in the control group [26.5% (13 cases) and 51.0% (25 cases)] (P=0.029 and 0.046, respectively). The detection rate of intestinal tube accumulation in the study group was lower than that in the control group [12.5% (6 cases) vs 38.9% (19 cases)] (P=0.003). There was no significant difference in the total incidence of complications (anastomotic leakage, abdominal infection, intestinal obstruction, pendant pneumonia and urinary tract infection) between the two groups [18.8% (9 cases) vs 24.5% (12 cases)] (P=0.493). There was no significant difference in 5-year cumulative survival rate between the study group and the control group (71.6% vs 68.2%, P=0.309). Conclusion: Pelvic peritoneum reconstruction can improve postoperative anal function and reduce intestinal tube accumulation in patients underwent laparoscopic low anterior resection of rectal adenocarcinoma with high safety and feasibility.

[A study of the clinical curative effect of nucleos(t)ide analogues treated to pegylated interferon-α add-on therapy in patients with chronic hepatitis B].

Objective: To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test. Results: A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance. Conclusion: Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log(10)IU/ml), HBsAg level at 24 weeks (≤ 0.92 log(10)IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log(10)IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log(10)IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model.

OBJECTIVES: To advance the initiative of ending the global epidemic, long-lasting HIV protection is needed through sustained release of antiretroviral drugs for months to years. We investigated in macaques the safety and efficacy of biodegradable polycaprolactone implants releasing tenofovir alafenamide for HIV pre-exposure prophylaxis (PrEP). METHODS: Implants were administered subcutaneously in the arm using a contraceptive trocar. Efficacy against vaginal simian-HIV (SHIV) infection was investigated in six pigtailed macaques that received two tenofovir alafenamide implants (0.35 mg/day), one in each arm, for a total release rate of tenofovir alafenamide at 0.7 mg/day. Macaques were exposed to SHIV twice weekly for 6 weeks. Statistical analyses were used to compare outcome with eight untreated controls. Histological assessments were performed on skin biopsies collected near implantation sites. RESULTS: Median (range) tenofovir diphosphate level in PBMCs was 1519 (1068-1898) fmol/106 cells. All macaques with tenofovir alafenamide implants were protected against vaginal SHIV infection. In contrast, 7/8 controls were infected after a median of 4 SHIV exposures (P = 0.0047). Histological assessment of tissues near tenofovir alafenamide implant sites showed inflammation and necrosis in 5/6 animals, which were not evident by visual inspection. CONCLUSIONS: We demonstrated complete protection against vaginal SHIV infection with two implants releasing a total of 0.7 mg of tenofovir alafenamide per day. We also identified tenofovir diphosphate concentrations in PBMCs associated with complete vaginal protection. Consistent with previous findings, we observed adverse local toxicity and necrosis near the tenofovir alafenamide implant site. Improved tenofovir alafenamide implants that are safe and maintain high efficacy have the potential to provide long-lasting protection against vaginal HIV infection.

Role of cytosolic carbonic anhydrase Ca17a in cardiorespiratory responses to CO2 in developing zebrafish (Danio rerio).

The sensing of environmental fluctuations and initiation of appropriate physiological responses is crucial to homeostasis. Neuroepithelial cells (NECs) in fishes are putative chemoreceptors, resembling mammalian Type I (glomus) cells, that respond in vitro to changes in O2, CO2, NH3, and pH. Cytosolic carbonic anhydrase (Ca17a) is thought to be involved in CO2 sensing owing to its presence in NECs. Zebrafish (Danio rerio) lacking functional Ca17a were generated via CRISPR/Cas9 technology and used to assess the role of Ca17a in initiating the cardiorespiratory responses to elevated CO2 (hypercapnia). Unfortunately, the homozygous knockout mutants (ca17a-/-) did not survive more than ∼12-14 days postfertilization (dpf), restricting experiments to early developmental stages (4-8 dpf). Changes in ventilation (fV) and cardiac (fH) frequency in response to hypercapnia (1% CO2) in wild-type (ca17a+/+), heterozygous (ca17a+/-) and ca17a-/- fish were used to investigate Ca17a-dependent CO2 sensing and downstream signaling. Wild-type fish exhibited hyperventilation during hypercapnia as indicated by an increase in fV. In the ca17a-/- fish, the hyperventilatory response was attenuated markedly but only at 8 dpf. Hypercapnic tachycardia was observed for all genotypes and did not appear to be influenced by the absence of Ca17a. Interestingly, ca17a-/- fish exhibited a significantly lower resting fH that became more pronounced as the fish aged. The decrease in resting fH was prevented ("rescued") when ca17a-/- embryos were injected with ca17a mRNA. Collectively, the results of this study support a role for Ca17a in promoting hyperventilation during hypercapnia in larval zebrafish and suggest a previously unrecognized role for Ca17a in determining resting heart rate.

Preventing adverse events of chemotherapy for gastrointestinal cancer by educating patients about the nocebo effect: a randomized-controlled trial.

BACKGROUND: Adverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events. METHODS: In this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms. RESULTS: General linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [- 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy. CONCLUSIONS: This study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events. TRIAL REGISTRATION: Retrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).

The relationship between hepatitis B virus serum DNA, RNA and quantitative hepatitis B surface antigen, and the predictive value for mother-to-child transmission: an observational cohort study.

OBJECTIVE: To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. DESIGN: An observational cohort study. SETTING: First Hospital of Jilin University. POPULATION: HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. METHODS: Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. RESULTS: Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P < 0.001), and HBV DNA (rs = 0.500; P < 0.001) and HBsAg (rs = 0.372; P < 0.001) were both correlated with HBV RNA. The areas under the curve for HBV DNA, HBsAg and HBV RNA for prediction of infection were 0.69 (95% CI 0.57-0.82), 0.63 (95% CI 0.51-0.76) and 0.65 (95% CI 0.52-0.78), respectively. Higher HBV DNA (odds ratio [OR] 4.77, 95% CI 1.44-15.86), higher HBsAg (OR 4.13, 95% CI 1.12-15.25) and higher HBV RNA (OR 3.19, 95% CI 1.09-9.32) were risk factors for HBV infection. Analysis of the HBV DNA-RNA-HBsAg Score revealed that it was an independent predictive factor for mother-to-child transmission (the OR of Score 3 was 8.81, 95% CI 2.79-27.82). CONCLUSION: HBV DNA, HBV RNA and HBsAg were correlated in HBeAg-positive pregnant women. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. We should pay special attention to pregnant women with high levels of all three markers. TWEETABLE ABSTRACT: HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. Special attention should be given to pregnant women with high levels of all three markers (HBV DNA, HBV RNA and HBsAg).

CT and MRI features of extraocular muscle granular cell tumour: preliminary experience in eight cases.

AIM: To characterise the computed tomography (CT) and magnetic resonance imaging (MRI) features, in particular the functional MRI characteristics, of extraocular muscle granular cell tumours (GCTs). MATERIALS AND METHODS: The CT (n=6) and MRI (n=8) features of eight extraocular muscle GCTs cofirmed at histopathology were analysed retrospectively. The imaging findings were evaluated with emphasis on the location, size, margin, shape, extent, bony change, internal architecture, enhancement pattern, and extent of lesions. Based on diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, the apparent diffusion coefficient (ADC) value of six lesions and time-intensity curve (TIC) of one lesion were reviewed. RESULTS: Immunohistochemistry revealed strong positivity for S-100 protein and a low Ki-67 index (2-5%) in all cases. Most of the lesions (7/8) were confined to the muscle belly with an ovoid shape. All of the tumours were isodense to cerebral grey matter and showed homogeneously mild enhancement on CT images. All lesions were hypointense to cerebral grey matter on T2-weighted imaging (T2WI) and showed homogeneously marked enhancement on contrast-enhanced T1-weighted imaging (T1WI). All lesions showed a hypo- or isointense signal on DWI images with a high b-value. The mean ADC of six lesions was (0.72 ± 0.14) × 10-3 mm2/s. The TIC of the case examined using DCE-MRI showed a plateau pattern (type II). CONCLUSION: A well-defined oval mass confined to the muscle belly with a hypointense signal on T2WI, homogeneously marked enhancement on contrast-enhanced T1WI, hypo- or isointense signal on DWI, and low ADC value is highly suggestive of a GCT.

Differentiation of malignant from benign orbital tumours using dual-energy CT.

AIM: To investigate the diagnostic accuracy of dual-energy computed tomography (DECT)-derived iodine concentration (IC), effective atomic number (Zeff), and spectral attenuation information for differentiating malignant and benign orbital tumours. MATERIALS AND METHODS: Data from 41 patients with orbital tumours from November 2019 to March 2021 were analysed retrospectively. Each patient underwent contrast-enhanced DECT using a 128-section dual-source computed tomography (DSCT) system. Dual-energy information, including IC, normalised iodine concentration (NIC), Zeff, virtual monoenergetic images (VMIs) reconstructed from 40 to 120 keV and slope (k) value were determined. Quantitative measurement of DECT parameters was undertaken by two independent radiologists blinded to clinical data. Differences in parameters were assessed using independent sample t-test. Diagnosis performance was calculated by the receiver operating characteristic (ROC) curve analysis. Radiation doses of conventional CT and DECT were compared by paired t-tests. RESULTS: Forty-one patients with histopathologically confirmed tumours were enrolled, including 10 malignant cases and 21 benign cases. Malignant orbital tumours exhibited significantly greater IC, NIC, Zeff, CT attenuation of VMIs at 40-105 keV, and k values compared to benign orbital tumours (p<0.05). In ROC analyses, 40 keV VMI demonstrated the highest diagnostic performance of single parameters (area under the ROC curve [AUC], 0.940), and combined parameters achieved the best performance (AUC, 0.971; sensitivity, 90%; specificity, 93.55%). Radiation doses were significantly reduced in DECT than conventional CT (p<0.001). CONCLUSIONS: Quantitative DECT analysis can be a useful technique, which yields excellent diagnostic accuracy, in the differentiation of malignant and benign orbital tumours with low radiation dose.

Detection of optrA and poxtA genes in linezolid-resistant Enterococcus isolates from fur animals in China.

The emergence of linezolid-resistant (LR) enterococci found in food of animal origin arouses attention, but little is known about LR enterococci in fur animals. A total of 342 Enterococcus faecalis and 265 E. faecium strains isolated from fur animals in China from 2015 to 2017 were investigated to determine if LR enterococci (≥16 µg ml-1 ) are present. Overall, two E. faecalis and 12 E. faecium among these isolates were resistant to linezolid. In addition, all LR isolates were classified as multidrug-resistant isolates. We further explore the resistance genes of the LR enterococci, four E. faecalis and two E. faecium isolates contained optrA gene. Two of them co-harboured optrA and poxtA genes. We detected virulence genes in LR enterococci were the following: asa1, cylA, esp, gelE and hyl, among which the highest carrying rate gene was asa1. Besides, all of the LR enterococci we tested had the biofilm-forming ability. It is worth noting that we detected a novel ST type ST2010 from E. faecium 82-2. These data show LR enterococci exist in fur animals and have unique characteristics.