Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer.

BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.

The effects of short video app-guided loving-kindness meditation on college students' mindfulness, self-compassion, positive psychological capital, and suicide ideation.

OBJECTIVE: The study investigated the effects of a short video app guided loving-kindness meditation (LKM) on college students' mindfulness, self-compassion, positive psychological capital, and suicide ideation. The purpose of the study is to investigate the intervention effect of LKM training on suicidal ideation among college students with the help of the short video application and to provide an empirical basis for the exploration of early suicide intervention strategies for college students. METHODS: We recruited 80 college students from a university in China. The final 74 eligible participants were divided into two groups: app use group (n = 37) and the control group (n = 37). The app group accepted an 8-week app use interference, while the control group underwent no interference. We measured four major variable factors (mindfulness, self-compassion, positive psychological capital, and suicide ideation) before and after the app use intervention. RESULTS: In the app group, self-compassion and positive psychological capital were significantly higher, and suicide ideation was significantly lower than the control group. In the control group, there were no noticeable differences in any of the four variables between the pre-test and post-test. CONCLUSIONS: Our findings demonstrate that the short video app guided LKM may help to improve self-compassion, and positive psychological capital, and reduce suicide ideation. The finding of the short video app-guided LKM's effect extends our understanding of the integrative effects of positive psychology and digital media on the reduction of suicide ideation.

First Report of Pseudocercospora paraguayensis Causing Leaf Spots on Bixa orellana from Chinese Mainland.

Bixa orellana L. is a traditional Chinese medicine. In December 2019, a leaf spot disease was observed on B. orellana from a field in Zhanjiang (21°18'12''N, 110°17'22''E), China. Disease incidence was around 85% (n = 100 investigated plants from about 30 hectares). Initial leaf spots were circular, and the center of the lesions was grayish-white with a purple black border. The coalescence of individual spots eventually led to leaf wilt. Ten symptomatic leaves from 10 plants were sampled. The margins of the samples were cut into 2 mm × 2 mm pieces, and the surfaces were disinfected with 75% ethanol for 30 sec, and 2% sodium hypochlorite for 60 sec. The the samples were then rinsed three times in sterile water, plated on potato dextrose agar (PDA), and incubated at 28 °C. Pure cultures were obtained by transferring the hyphal tips to new PDA plates. Three representative isolates (BOPP-1, BOPP-2, and BOPP-3) were used for further study. The colonies of isolates on PDA were dark olive green with off-white aerial mycelia after 7 days at 28 °C. Conidia were solitary, smooth to verrucous, olive to light brown, slightly curved, narrowly obclavate, apex obtuse, base obconic-truncate, had 2-4 septa, and 30.4-55.5×2.0-3.5 µm in size.. These morphological characteristics showed did not differ from the description of Pseudocercospora paraguayensis (Crous et al. 1997). For molecular identification, the internal transcribed spacer (ITS) region, the translation elongation factor 1-α (TEF1) gene, and actin (ACT) gene were amplified using primer pairs ITS1/ITS4 (White et al., 1990), EF1/EF2 ( O'Donnell et al. 1998), and ACT-512F/ACT-783R (Carbone and Kohn, 1999) and sequenced from DNA extracted from the three isolates, respectively. Sequences were deposited in GenBank under accession no. MZ363823-MZ363825 (ITS), MZ614954-MZ614956 (TEF1), and MZ614951-MZ614953 (ACT). A phylogenetic tree was generated on the basis of the concatenated data from the sequences of ITS, TEF1, and ACT that the three isolates were nested within the clade containing the type specimen of P. paraguayensis (CBS 111286) but not within P. bixae (the type specimen CPC 25244). Pathogenicity was tested through in vivo experiments. Inoculation and control seedlings (n = 5, 1-month-old) were sprayed with a spore suspension (1 × 105 per ml) of P. paraguayensis and sterile distilled water (control), respectively, until run-off (Fang. 1998). The plants were grown in pots in a greenhouse at 28°C, with at approximately 80% RH. The test was performed three times. Symptoms similar to those in the field were observed on the inoculated plants after two weeks. The control plants remained healthy. The fungus was re-isolated from the infected leaves and confirmed as the same isolates by morphological and comparison of ITS sequences with 100% identical to those of isolates. No original fungi were isolated from the control plants. A previous study reported that P. paraguayensis caused leaf spots on pistachio and eucalypts, and the fungus causing the leaf spots of B. orellana was redescribed as P. bixae (Crous et al. 2019). However, multilocus phylogenetic analyses differentiated P. paraguayensis from P. bixae. In the present study, P. paraguayensis was distinguished from P. bixae due to the absence of catenulate conidia and the presence of finely verruculose conidia (Crous et al. 2013). P. eucalypti as a synonyms was reported in Taiwan (www.MycoBank.org). The current study is the first to report P. paraguayensis causing leaf spots on B. orellana from Chinese Mainland. This finding will help to provide a scientific basis for the disease detection.

Design, synthesis and biological evaluation of fluorinated selective estrogen receptor degraders (FSERDs) --- A promising strategy for advanced ER positive breast cancer.

Although endocrine therapies involving pharmaceuticals, such as tamoxifen and aromatase inhibitors, had initially demonstrated good responses in patients with estrogen receptor-positive (ER+) breast cancer, they often led to drug resistance. ER plays a vital role in the progression of metastatic diseases. Fulvestrant, a first generation selective estrogen receptor degrader (SERD), can effectively downregulate the ER protein and inhibit its downstream signaling pathways. However, as the drug needs to be intramuscularly injected, its widespread use is limited owing to poor patient compliance. Herein, we described a novel class of orally bioavailable fluorine-substituted SERDs that exhibit improved pharmacokinetic profiles. We substituted the hydroxyl group of clinical SERD candidate 6 with a fluorine atom to diminish phase II metabolism. The subsequent structure-activity relationship (SAR) investigation identified 22h and 27b, which can effectively degrade ER in a dose-dependent manner and exhibit considerable antiproliferative potency and efficacy in vitro and in vivo. The excellent pharmacokinetic profiles of 27b render it promising candidate of clinically useful oral SERD.

The effects of short video app-guided loving-kindness meditation on college students' mindfulness, self-compassion, positive psychological capital, and suicide ideation

Abstract Objective The study investigated the effects of a short video app guided loving-kindness meditation (LKM) on college students' mindfulness, self-compassion, positive psychological capital, and suicide ideation. The purpose of the study is to investigate the intervention effect of LKM training on suicidal ideation among college students with the help of the short video application and to provide an empirical basis for the exploration of early suicide intervention strategies for college students. Methods We recruited 80 college students from a university in China. The final 74 eligible participants were divided into two groups: app use group (n = 37) and the control group (n = 37). The app group accepted an 8-week app use interference, while the control group underwent no interference. We measured four major variable factors (mindfulness, self-compassion, positive psychological capital, and suicide ideation) before and after the app use intervention. Results In the app group, self-compassion and positive psychological capital were significantly higher, and suicide ideation was significantly lower than the control group. In the control group, there were no noticeable differences in any of the four variables between the pre-test and post-test. Conclusions Our findings demonstrate that the short video app guided LKM may help to improve self-compassion, and positive psychological capital, and reduce suicide ideation. The finding of the short video app-guided LKM's effect extends our understanding of the integrative effects of positive psychology and digital media on the reduction of suicide ideation.

Intermittent vibrations accelerate fracture healing in sheep.

PURPOSE: To investigate the effect of intermittent vibration at different intervals on bone fracture healing and optimize the vibration interval. METHODS: Ninety sheep were randomized to receive no treatment (the control group), incision only (the sham control group), internal fixation with or without metatarsal fracture (the internal fixation group), and continuous vibration in addition to internal fixation of metatarsal fracture, or intermittent vibration at 1, 2, 3, 5, 7 and 17-day interval in addition to internal fixation of metatarsal fracture (the vibration group). Vibration was done at frequency F=35 Hz, acceleration a=0.25g, 15 min each time 2 weeks after bone fracture. Bone healing was evaluated by micro-CT scan, bone microstructure and mechanical compression of finite element simulation. RESULTS: Intermittent vibration at 7-day interval significantly improved bone fracture healing grade. However, no significant changes on microstructure parameters and mechanical properties were observed among sheep receiving vibration at different intervals. CONCLUSIONS: Clinical healing effects should be the top concern. Quantitative analyses of bone microstructure and of finite element mechanics on the process of fracture healing need to be further investigated.

Intermittent vibrations accelerate fracture healing in sheep

Purpose: To investigate the effect of intermittent vibration at different intervals on bone fracture healing and optimize the vibration interval. Methods: Ninety sheep were randomized to receive no treatment (the control group), incision only (the sham control group), internal fixation with or without metatarsal fracture (the internal fixation group), and continuous vibration in addition to internal fixation of metatarsal fracture, or intermittent vibration at 1, 2, 3, 5, 7 and 17-day interval in addition to internal fixation of metatarsal fracture (the vibration group). Vibration was done at frequency F=35 Hz, acceleration a=0.25g, 15 min each time 2 weeks after bone fracture. Bone healing was evaluated by micro-CT scan, bone microstructure and mechanical compression of finite element simulation. Results: Intermittent vibration at 7-day interval significantly improved bone fracture healing grade. However, no significant changes on microstructure parameters and mechanical properties were observed among sheep receiving vibration at different intervals. Conclusions: Clinical healing effects should be the top concern. Quantitative analyses of bone microstructure and of finite element mechanics on the process of fracture healing need to be further investigated.(AU)

Type II Abernethy Malformation in a Patient with Primary Budd-Chiari Syndrome.

Budd-Chiari syndrome (BCS) is a heterogeneous group of disorders characterized by hepatic venous outflow obstruction. Abernethy malformation is a congenital vascular malformation defined by diversion of portal blood away from the liver. Both conditions are rare vascular diseases. We report here the first case of a patient with combined type II Abernethy malformation and BCS from China. The inferior vena cava obstruction was treated with percutaneous balloon angioplasty; close follow-up was elected for the Abernethy malformation.

Intermittent vibrations accelerate fracture healing in sheep

Abstract Purpose: To investigate the effect of intermittent vibration at different intervals on bone fracture healing and optimize the vibration interval. Methods: Ninety sheep were randomized to receive no treatment (the control group), incision only (the sham control group), internal fixation with or without metatarsal fracture (the internal fixation group), and continuous vibration in addition to internal fixation of metatarsal fracture, or intermittent vibration at 1, 2, 3, 5, 7 and 17-day interval in addition to internal fixation of metatarsal fracture (the vibration group). Vibration was done at frequency F=35 Hz, acceleration a=0.25g, 15 min each time 2 weeks after bone fracture. Bone healing was evaluated by micro-CT scan, bone microstructure and mechanical compression of finite element simulation. Results: Intermittent vibration at 7-day interval significantly improved bone fracture healing grade. However, no significant changes on microstructure parameters and mechanical properties were observed among sheep receiving vibration at different intervals. Conclusions: Clinical healing effects should be the top concern. Quantitative analyses of bone microstructure and of finite element mechanics on the process of fracture healing need to be further investigated.

Modelling opportunity: An examination of quadratic effects of adolescent Venezuelan substance use.

INTRODUCTION AND AIMS: Numerous studies have found a linear relationship between an exposure opportunity and age of first drug use. This study further tests this relationship by exploring whether a quadratic exposure opportunity best fits the data on age of first use and whether gender moderates this relationship. That is, is there a peak age in which the transition to use occurs for male compared to female adolescents? DESIGN AND METHODS: A sample of 1716 adolescents from 14 public and private schools, representative of two school districts in Caracas, Venezuela, was examined using a zero-inflated Poisson modelling approach to test for quadratic effects. A series of models were tested for each set of substances (alcohol, tobacco and other drugs) to assess whether a quadratic model has better predictive ability than linear models and to test whether gender moderates the quadratic relationship. RESULTS: After controlling for common covariates, the quadratic models for alcohol indicated the peak age of transition from an exposure opportunity to use was 10-years of age in this Venezuelan sample. Gender did not moderate these models suggesting an important move toward gender equality in substance use. DISCUSSION AND CONCLUSIONS: Focused efforts on preventing exposure to alcohol use during these windows of rapid transition is likely to have the greatest impact on delaying age of onset, which will reduce the overall prevalence of alcohol related problems among adolescents.

Opportunities to use drugs and the transition to drug use among adolescents from Caracas, Venezuela.

Few studies have examined exposure to drug use and the lag between exposure and use. This paper estimates prevalence of opportunity to use a substance, for use, and for use given an opportunity to use among a sample of Venezuelan adolescents. Several covariates on the opportunity to use and the transition to use are also examined. Findings show that lifetime prevalence of substance use among Venezuelan adolescents increases dramatically and more closely resembles rates among US and European samples when having had an opportunity to use was taken into account. A majority of youth who transitioned to use did so the same year exposure occurred, and females had a shorter time difference compared to males. Covariates primarily predicted exposure rather than having used after controlling for exposure, and their effects varied by substance. Implications for prevention efforts are discussed.

Efeito imediato da manipulação thrust aplicada na coluna cervical alta sobre a abertura ativa da boca: ensaio clínico randomizado / Immediate effects of upper cervical thrust manipulation on active mouth opening: randomized clinical trial

Objetivo - Determinar a influência imediata da técnica de alta velocidade e baixa amplitude (HVLA) aplicada na coluna cervical alta na abertura ativa da boca. As desordens temporomandibulares são afecções da articulação temporomandibular e suas estruturas periarticulares, sendo um dos sinais característicos a redução na amplitude de depressão da mandíbula. Métodos - Participaram do estudo 83 voluntários com idade entre 18 e 33 anos e dor na coluna cervical, distribuídos aleatoriamente em dois grupos, o experimental, submetidos a técnica HVLA (n= 41) e o grupo placebo (n=42). Cada sujeito teve a abertura da boca mensurada três vezes antes e após o tratamento por um avaliador cego. Resultados - O grupo em que a técnica HVLA foi aplicada na coluna cervical alta promoveu aumento imediato na abertura da boca, visto que a ADM de depressão da mandíbula no momento após intervenção, como a diferença pré e pós-intervenção foram maiores no grupo experimental comparado ao grupo placebo. Conclusão - A aplicação da HVLA sobre os músculos suboccipitais pode promover aumento na abertura da boca em sujeitos sintomáticos na região da coluna cervical imediatamente após a intervenção.

Objective - To determine the immediate influence of high velocity and low aplitude (HVLA) technique applied to upper cervical spine in active mouth opening. Temporomandibular disorders are affections of the temporomandibular joint and periarticular structures, which one of signs is a depression ampleness reduction of the jaw. Methods - The study included 83 volunteers aged between 18 and 33 years and pain inthe cervical spine, divided in two groups, the experimental subject to HVLA (n = 41) and placebo (n = 42 ). Each subject had the opening of the mouth measured three times before and after treatment by a blinded evaluator. Results - The group which HVLA was applied to the upper cervical spine promoted and immediate increase in mouth opening, since the ADM of depression at the time of the jaw after the intervention, as the difference before and after intervention, were higher in the experimental group compared to placebo group. Conclusion - The application of the HVLA on the upper cervical spine may promote an increase in mouth opening in subjects with symptomatic cervical spine region immediately after the intervention.

Early onset of subclinical atherosclerosis in young persons with type 1 diabetes.

OBJECTIVE: To evaluate the degree of atherosclerosis and its risk factors in adolescents and young adults with type 1 diabetes. STUDY DESIGN: We measured carotid artery intima-media thickness (IMT) in 142 subjects with type 1 diabetes (mean [SD] age = 16.0 [2.6] years) and 87 control subjects (18.8 [3.1] years). Fasting lipid and homocysteine levels, degree of glycemic control, blood pressure, and body mass index were measured in persons with diabetes. RESULTS: The mean carotid IMT was greater in persons with diabetes ( P = .002). Among subjects with type 1 diabetes, lipid levels were significantly higher in female subjects compared with male subjects. The mean carotid IMT was significantly higher in persons with a diabetic complication (including hypertension, retinopathy, or microalbuminuria). In male subjects but not female subjects, HDL cholesterol and the LDL/HDL ratio were correlated with carotid IMT. CONCLUSIONS: Adolescents with type 1 diabetes have increased atherosclerosis compared with control subjects. Risk factors for increased carotid IMT in these younger patients include diabetic complications and HDL cholesterol and the LDL/HDL ratio, which may be sex-specific.