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Purpose Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT 3 RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT 3 RAs in CINV prophylaxis. Methods A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT 3 RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT 3 RA-related adverse events. Results Sixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT 3 RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints. Conclusions Palonosetron is safer and more efficacious than other 5-HT 3 RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.

Metastases from papillary thyroid cancers (PTC) are an uncommon occurrence. When metastases do occur, the most common sites are to the lung and bone; conversely, metastases to the brain from a thyroid primary are extremely rare. Complications can arise from bone metastases, including pathological fractures. Treatment of fractures consists of surgical intervention and/or radiation treatment. The decision of whether or not to operate on a patient is affected by the patient's condition and survival expectancy; for the latter, brain metastases are a known marker of poor prognosis. In this case report, the authors present, the case of a 78 year-old male with PTC, who was diagnosed with both brain and bone metastases and suffered from a pathological fracture to the right humerus. The patient was treated with radiation treatment of 20 Gy in five fractions to the whole brain and to the right humerus. Current treatment strategies for patients in this population are reviewed and discussed.

Following arthroplasty, complications resulting from wear of the prosthesis, namely particle disease, can arise. Due to the rarity of the disease, its similar appearance to a lytic lesion in diagnostic imaging, and similar clinic presentation to bone metastases, it can be misdiagnosed. The authors present, the case of a 47 year-old woman who presented with what was believed to be a lytic lesion, but was later found to be consistent with particle disease.

Cancer of unknown primary (CUP) is a common malignancy, that accounts for approximately 3% to 5% of all cancer diagnosis. When patients suffer from pathological fractures secondary to bone metastases, specifically those with poor performance status, surgery is usually not indicated due to poor prognosis. Instead, pain management may become the primary concern. In this report, the authors present, the case of a 65 year old male with widespread bone metastases from a CUP. The patient suffered from severe bone pain and pathological fractures in the right acetabulum as well his right humerus. Consequently, he was unable to walk and felt extremely weak. The patient originally was scheduled to receive palliative radiotherapy of 30 Gy in 10 fractions, but the dose was later reduced to 20 Gy in 5 fractions.

Bone metastases occur in up to 90% of patients with advanced breast or prostate cancer. Spinal cord compression (SCC) is an oncologic emergency and is considered a complication of bone metastases. If SCC is left untreated, it can result in a loss of feeling, motor control, and eventually paralysis. In most cases, cancer will be first diagnosed in early stages. The authors present, the case of a 71 year-old male who, upon initial presentation, had a spinal cord compression and associated lower extremity weakness and gait difficulty. At this time, he had no prior history of cancer or confirmed tissue diagnosis of cancer.

China's reform era has coincided with an emergence of a Chinese Communist Party-State ideological discourse concerning \"population quality.\" Claims and accusations of 'low quality' are particularly targeted at rural migrant women who have been migrating to Chinese cities at an increasing rate. This investigation attempts to delineate to what extent this is a story of complete domination of the hearts and minds. To what extent do the women themselves internalize these claims of low 'quality?'The thesis has been built around fieldwork conducted in the Beijing household services sector. Known as an industry for perpetrating unjust labor conditions for women, this site proves to be an appropriate site to explore a discourse that attempts to justify these conditions with claims of women's low 'quality.' It will analyze various manifestations of the suzhi discourse on-the-ground, as experienced the household service agency, women's organizations, and the migrant women domestic workers themselves. Analysis of each of the players' relationship to the discourse is complex: there are instances of submission and resistance; defiance and internalization; and nuances and generalizations.

The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression. Intratumoural heterogeneity is a feature of liver cancer. Here, the authors demonstrate that heterogeneity exists at the immune cell level in liver cancer and show that tumours with high intratumoural immune heterogeneity demonstrated an immune suppressive microenvironment, which was associated with tumour evolution and a poor prognosis.

The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence. Method: Sixty-four adolescents were stratified into higher- or lower-childhood-trauma groups. Inhibitory control was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging assessed neural correlates of stress in adolescents. Results: Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, associated with Stroop Color-Word task performance in prior meta-analyses, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r = −.23, p = .04). Childhood trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction = −1.26, p = .02, 95%CI = −2.33,-0.20), where Stroop errors were inversely associated with brain activation among those with higher childhood trauma (simple slopes = −.83, p = .007, 95%CI = −1.40,-0.25). Low stress-related rCZa activation inversely (R2 = 0.19, b = −0.43, p = .001, 95%CI = −4.11,-1.06) and Stroop errors directly (R2 = 0.09, b = 0.27, p = .048, 95%CI = 0.02, 5.8) associated with baseline subjective anxiety while controlling for childhood trauma. Conclusions: This is the first study to demonstrate a moderating role of childhood trauma on the relationship between inhibitory control and stress-related ACC activation. Childhood trauma may portend neurodevelopmental changes that impede recruitment of control-associated ACC-functioning during distress, which may relate to dysregulation of stress-induced affective responses. Further work is needed to elucidate relationships between childhood trauma and addictive behaviors precipitated by stress. •A novel method found trauma moderated an inhibition-ACC stress-reactivity pathway.•Higher-trauma youth with poor inhibition developed lower ACC stress reactivity.•Lower ACC stress reactivity portended greater subjective anxiety.•Using a meta-analysis-defined ROI approach improves generalizability of findings.•Childhood trauma burdens ACC-related stress regulation.

Background Dysregulation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) form the basis of immune-mediated inflammatory diseases. Vitex trifolia L. is a medicinal plant growing in countries such as China, India, Australia and Singapore. Its dried ripe fruits are documented in Traditional Chinese Medicine to treat ailments like rhinitis and dizziness. Its leaves are used traditionally to treat inflammation-related conditions like rheumatic pain. Objective This study aimed to investigate the effects of V. trifolia leaf extracts prepared by different extraction methods (Soxhlet, ultrasonication, and maceration) in various solvents on cytokine production in human U937 macrophages, and identify phytoconstituents from the most active leaf extract. Methods Fresh leaves of V. trifolia were extracted using Soxhlet, ultrasonication, and maceration in hexane, dichloromethane, methanol, ethanol or water. Each extract was evaluated for its effects on TNF-α and IL-1β cytokine production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. The most active extract was analyzed and further purified by different chemical and spectroscopic techniques. Results Amongst 14 different leaf extracts investigated, extracts prepared by ultrasonication in dichloromethane and maceration in ethanol were most active in inhibiting TNF-α and IL-1β production in human U937 macrophages. Further purification led to the isolation of artemetin, casticin, vitexilactone and maslinic acid, and their effects on TNF-α and IL-1β production were evaluated. We report for the first time that artemetin suppressed TNF-α and IL-1β production. Gas chromatography-mass spectrometry analyses revealed the presence of eight other compounds. To the best of our knowledge, this is the first report of butylated hydroxytoluene, 2,4-di- tert -butylphenol, campesterol and maslinic acid in V. trifolia leaf extracts. Conclusions In conclusion, leaf extracts of V. trifolia obtained using different solvents and extraction methods were successfully investigated for their effects on cytokine production in human U937 macrophages. The findings provide scientific evidence for the traditional use of V. trifolia leaves (a sustainable resource) and highlight the importance of conservation of medicinal plants as resources for drug discovery. Our results together with others suggest further investigation on V. trifolia and constituents to develop novel treatment strategies in immune-mediated inflammatory conditions is warranted.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21556-y.