Climate-driven variability of the Southern Ocean CO2 sink.

The Southern Ocean is a major sink of atmospheric CO2, but the nature and magnitude of its variability remains uncertain and debated. Estimates based on observations suggest substantial variability that is not reproduced by process-based ocean models, with increasingly divergent estimates over the past decade. We examine potential constraints on the nature and magnitude of climate-driven variability of the Southern Ocean CO2 sink from observation-based air-sea O2 fluxes. On interannual time scales, the variability in the air-sea fluxes of CO2 and O2 estimated from observations is consistent across the two species and positively correlated with the variability simulated by ocean models. Our analysis suggests that variations in ocean ventilation related to the Southern Annular Mode are responsible for this interannual variability. On decadal time scales, the existence of significant variability in the air-sea CO2 flux estimated from observations also tends to be supported by observation-based estimates of O2 flux variability. However, the large decadal variability in air-sea CO2 flux is absent from ocean models. Our analysis suggests that issues in representing the balance between the thermal and non-thermal components of the CO2 sink and/or insufficient variability in mode water formation might contribute to the lack of decadal variability in the current generation of ocean models. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Developing flexible models for genetic evaluations in smallholder crossbred dairy farms.

The productivity of smallholder dairy farms is very low in developing countries. Important genetic gains could be realized using genomic selection, but genetic evaluations need to be tailored for lack of pedigree information and very small farm sizes. To accommodate this situation, we propose a flexible Bayesian model for the genetic evaluation of milk yield, which allows us to simultaneously account for nongenetic random effects for farms and varying SNP variance (BayesR model). First, we used simulations based on real genotype data from Indian crossbred dairy cattle to demonstrate that the proposed model can separate the true genetic and nongenetic parameters even for small farm sizes (2 cows on average) although with high standard errors in scenarios with low heritability. The accuracy of genomic genetic evaluation increased until farm size was approximately 5. We then applied the model to real data from 4,655 crossbred cows with 106,109 monthly test day milk records and 689,750 autosomal SNPs. We estimated a heritability of 0.16 (0.04) for milk yield and using cross-validation, a genomic estimated breeding value (GEBV) accuracy of 0.45 and bias (regression of phenotype on GEBV) of 1.04 (0.26). Estimated genetic parameters were very similar using BayesR, BayesC, and genomic BLUP approaches. Candidate genes near the top variants, IMMP2L and ARHGEF2, have been previously associated with milk protein composition, mastitis resistance, and milk cholesterol content. The estimated heritability and GEBV accuracy for milk yield are much lower than those from intensive or pasture-based systems in many countries. Further increases in the number of phenotyped and genotyped animals in farms with at least 2 cows (preferably 3-5, to allow for dropout of cows) are needed to improve the estimation of genetic effects in these smallholder dairy farms.

Effects of lysolecithins on performance, egg quality, blood profiles and liver histopathology in late-phase laying hens.

1. This study investigated the effects of lysolecithins (LL) on performance, egg quality, blood profiles, relative organ weight and liver histopathology in laying hens.2. A total of 480 healthy 65-week-old Lohmann laying hens were randomly allocated into four treatments in a 2 × 2 factorial arrangement design with two levels of energy (AMEn, 11.08 MJ/kg and 12.94 MJ/kg) and two levels of LL (0 and 0.05%).3. Birds fed high energy diets had lower (P < 0.05) average daily intake and feed conversion rate during weeks 0-4, 5-8 and 0-8, but higher (P < 0.05) average egg weight (AEW) during trial weeks 0-4. There was an interaction in (P < 0.05) AEW during trial weeks 0-14 and 0-8 for energy and LL. The high energy diets increased yolk colour at the end of weeks 2 and 4, while addition of LL increased albumen height at the end of week 2. There was an interaction (P < 0.05) in yolk colour between energy and LL at the end of week 2. There was an interaction (P < 0.05) in serum superoxide dismutase and LDL-C throughout the experiment.4. The high energy diets increased (P < 0.05) the relative weight of abdominal fat compared with low energy diets. The high energy diets increased (P < 0.05) liver ether extract content and liver pathological injury score compared with low energy diets at the end of week 8, while the addition of LL decreased (P < 0.05) liver pathological injury score.5. The supplementation of LL in high energy diets could alleviate some negative effects on liver injury in late laying hens.

Aetiology of tinea capitis in China: a multicentre prospective study.

BACKGROUND: Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time. OBJECTIVES: This study aimed to clarify the current epidemiological characteristics and pathogen spectrum of tinea capitis in China. METHODS: A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory. RESULTS: Among all enrolled patients, 74·1% of the cases were in patients aged 2-8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province. CONCLUSIONS: Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.

Long-term, durable, absolute Psoriasis Area and Severity Index and health-related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. OBJECTIVES: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab. METHODS: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. RESULTS: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. CONCLUSIONS: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.

[Clinical analysis of primary lung tumors in 56 children].

Objective: To investigate the clinical manifestation, pathological type, treatment and prognosis of primary lung tumors in children. Methods: We collected and retrospectively analyzed the clinical manifestation, pathological type, therapeutic method and prognosis of 56 primary lung tumors patients who diagnosed from 2009 to 2019 in Guangzhou Women and Children Medical Center. Results: There were 56 patients identified as the primary lung tumors, including pleuropulmonary blastoma (PPB, n=28), pulmonary inflammatory myofibroblastic tumor(IMT, n=20), mucoepidermoid carcinoma(n=6), infantile hemangioma (n=1), pulmonary sclerosing hermangioma(n=1). Respiratory symptoms were the most manifestation at the time of diagnosis including 26 patients with cough, 3 with hemoptysis, and 17 with dyspnea. Others included 15 with fever, 3 with chest pain, and 2 with epigastiric pain. The primary tumor of 18 cases were located in the lower lobe of left lung, 11 cases in the lower lobe of right lung, 10 cases in the upper lobe of left lung, 7 cases in the upper lobe of right lung, 6 cases in the middle lobe of right lung, and 4 cases in pulmonary hilum. Among the 56 patients, 41 patients underwent thoracotomy, 13 thoracoscopy, and 2 fiberoptic bronchoscopy. Five patients with type Ⅰ PPB were still alive at the end of follow-up without chemotherapy. Among 5 patients with type Ⅱ PPB, 2 patients without chemotherapy died after recurrence, 3 patients suffered postoperative chemotherapy were still alive at the end of follow-up. All of the 18 patients with type Ⅲ PPB underwent postoperative chemotherapy with IVADo regimen. Recurrence occurred in 6 cases, distant metastasis occurred in 3 cases, and cancer-related deaths occurred in 8 cases. For 20 patients with IMT, recurrence occurred in 5 of 13 patients experienced wedge resection, 1 of 6 patients experienced lobectomy and 1 of 6 underwent fiberoptic bronchoscopy, respectively. For 6 mucoepidermoid carcinoma patients, lobectomy was carried on 5 patients, wedge resection on 1 patient, all of them were still alive at the end of follow-up. One hermangioma patient underwent fiberoptic bronchoscopy and other 1 sclerosing hermangioma patient underwent wedge resection, both of them were still alive at the end of follow-up. Conclusions: The clinical manifestations of the primary lung tumors in children are nonspecific. Complete resection and achieving negative marginattribute to the excellent outcome. Adjunctive treatment such as chemotherapy is necessary for patients with type Ⅱ and type Ⅲ PPB.

Comparison of therapeutic efficacy and mechanism of paclitaxel alone or in combination with methotrexate in a collagen-induced arthritis rat model.

OBJECTIVE: To compare the therapeutic efficacy of paclitaxel (PTX) alone to its combination with methotrexate (MTX) on rheumatoid arthritis. METHODS: A collagen-induced arthritis (CIA) rat model was established by induction of type II collagen. Rats were divided into blank control group, CIA model group, MTX group 1 mg/kg, PTX 1.5 mg/kg, PTX 2.5 mg/kg, PTX 3.5 mg/kg, and MTX 1 mg/kg + PTX 3.5 mg/kg, with 10 rats per group. The inflammation of the ankle joint was analyzed by H&E staining and interleukin (IL)-1ß and IL­6 expression was detected by immunohistochemistry. TUNEL assay was performed to detect synovial tissue cell apoptosis after administration of PTX and MTX either alone or in combination. TLR4 and p­NF-κBp65 protein expression in synovial tissue and the changes of serum IL­1ß, IL­6, IL­12, MMP­3, and TNFα protein factors were detected by western blot and ELISA, respectively. RESULTS: PTX and MTX improved histopathological changes in CIA rats. Besides, the apoptosis rate of synovial tissue cells in the PTX 3.5 mg/kg group was more than that of the PTX + MTX group. Immunohistochemistry and western blot results indicated that PTX and MTX reduce the expression rate of IL­6 and IL­1ß and downregulate TLR4 and p­NF-κBp65 protein expression. Furthermore, TLR4 and p­NF-κBp65 reduced the concentration of MMP­3, IL­12, IL­6, IL1­ß, and TNFα. CONCLUSION: Both PTX and MTX exert significant suppression on rheumatoid arthritis, and the combined effect of the two drugs is weaker than that of PTX alone. Moreover, intraperitoneal injection of PTX 3.5 mg/kg every other day was the optimal dose observed in this study.

[Safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules: a retrospective analysis based on propensity score matching].

Objective: To evaluate the safety and feasibility of robotic-assisted thoracoscopic day surgery for pulmonary nodules. Methods: Clinical data of 523 patients with pulmonary nodule underwent robotic-assisted thoracoscopic surgery in the Department of Thoracic Surgery, Xiangya Hospital, Central South University from January 2021 to June 2022 were retrospectively analyzed, which including 223 males and 300 females, aged from 19 to 72 (54.0±11.7) years. Those patients were divided into the day surgery group (DSG) and inpatient surgery group (ISG) according to perioperative management methods. Propensity score matching (PSM) (1∶2) was performed according to the general baseline information, T stage of the tumor, surgery approach, and tumor position, and a total of 178 patients were finally included. Clinical outcomes of DSG were observed. The differences in incidence of postoperative complications, treatment-related costs and resource consumption between DSG and ISG were compared. Subgroup analysis was performed according to surgery method to evaluate the difference between DSG and ISG in lobectomy and sublobectomy. Results: In 81 cases DSG, eight patients were transferred to thoracic surgery ward, and the day surgery discharge rate was 90% (73/81). There was no statistically significant difference in incidence of postoperative complications between DSG and ISG (P=0.612). The length of stay after surgery, period of chest draining, average hospital cost, and drug cost of DSG were statistically significant lower than ISG, ((2.19±0.84) vs (4.74±1.81) days, (1.70±0.65) vs (3.45±1.85) days, (6.64±0.74) vs (8.29±0.97)×104 CNY, (0.35±0.07) vs (0.69±0.18)×104 CNY), respectively(all P<0.05). The drainage volume and VAS score at discharge in DSG and ISG group were(220.47±120.02) ml and(242.21±129.96) ml, 1.68±0.79 and 1.64±0.91, respectively, with no statistically significant difference (P>0.05). In subgroup analysis, there was no statistically significant difference in incidence of postoperative complications, drainage volume after surgery and VAS score at discharge between DSG and ISG both for lobectomy and sublobectomy patients. And the results of the length of stay after surgery, period of chest draining, and drug cost in DSG were also significantly lower than ISG (P<0.05). Conclusions: Robotic-assisted thoracoscopic day surgery for pulmonary nodule is safe and feasible, with the advantage of short length of stay after surgery, short period of chest draining, less average hospital cost and drug cost. There is no difference in incidence of postoperative complications between DSG and ISG.

Cascade of care of people diagnosed with HIV in New Zealand between 2006 and 2017.

OBJECTIVES: We estimated the proportion of people reported with HIV in New Zealand between 2006 and 2017, and alive in 2017-2019, who were on antiretroviral therapy (ART) and had a suppressed viral load (VL), and explored their associated characteristics. METHODS: Data were anonymously linked to information on ART and VL within the data collection period (January 2017 to August 2019) using the National Health Index (NHI), Ministry of Health and laboratory datasets, as well as information from clinical specialists. Logistic regression was used to test for associations. Sensitivity analyses were undertaken to estimate the range for the key proportions. RESULTS: Overall, 2355 people were reported with HIV, of whom 116 (5%) had died, 337 (14%) were overseas, and 1701 (72%) were alive in New Zealand; for the remaining 201 (9%) the outcome was unknown. Clinical data were available for 1490 people (87.6%): 1408 (94.5%) were on ART, 11 (< 1%) were not on ART, and for 71 (4.8%) this was unknown. Of those on ART, 1156 (82.1%) had a suppressed VL (< 200 copies/mL), 34 (2.4%) were unsuppressed, and for 218 (15.5%) this was unknown. The estimate of the proportion on ART ranged from 99% to 78%, and those with a suppressed VL ranged from 98% to 78%. CONCLUSIONS: Among people with HIV in New Zealand who are under care, a high proportion were on ART and had suppressed VL. Increasing collection of NHIs and better linkage with laboratory information will reduce the number with unknown information and provide more complete VL results in the future.

Long-term efficacy and safety of risankizumab for the treatment of moderate-to-severe plaque psoriasis: interim analysis of the LIMMitless open-label extension trial beyond 3 years of follow-up.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long-term evaluation to assess the durability of their efficacy and safety profiles over time. OBJECTIVES: To evaluate the long-term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. METHODS: LIMMitless is an ongoing, phase III, open-label extension study evaluating the long-term efficacy and safety of RZB in adults with moderate-to-severe plaque psoriasis following multiple phase II/III studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥ 90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90 and PASI 100), static Physician's Global Assessment of clear or almost clear (sPGA 0/1) and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. The study is registered at ClinicalTrials.gov (identifier: NCT03047395). RESULTS: Of 955 patients randomized to RZB 150 mg in the base studies, 897 patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI 90, 54·4% achieved PASI 100, 85·2% achieved sPGA 0/1, and 78·4% achieved DLQI 0/1 using modified nonresponder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long-term treatment and comparable with those identified in the base studies. CONCLUSIONS: Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks.

Defining trajectories of response in patients with psoriasis treated with biologic therapies.

BACKGROUND: The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed. OBJECTIVES: To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management. METHODS: We applied latent class mixed modelling to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials. RESULTS: We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories. CONCLUSIONS: These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.

Validation of superior reference genes for qRT-PCR and Western blot analyses in marine Emiliania huxleyi-virus model system.

AIMS: To search for a set of reference genes for reliable gene expression analysis in the globally important marine coccolithophore Emiliania huxleyi-virus model system. METHODS AND RESULTS: Fifteen housekeeping genes (CDKA, CYP15, EFG3, POLAI, RPL30, RPL13, SAMS, COX1, GPB1-2, HSP90, TUA, TUB, UBA1, CAM3 and GAPDH) were evaluated for their stability as potential reference genes for qRT-PCR using ΔCt, geNorm, NormFinder, Bestkeeper and RefFinder software. CDKA, TUA and TUB genes were tested as loading controls for Western blot in the same sample panel. Additionally, target genes associated with cell apoptosis, that is metacaspase genes, were applied to validate the selection of reference genes. The analysis results demonstrated that putative housekeeping genes exhibited significant variations in both mRNA and protein content during virus infection. After a comprehensive analysis with all the algorithms, CDKA and GAPDH were recommended as the most stable reference genes for E huxleyi virus (EhV) infection treatments. For Western blot, significant variation was seen for TUA and TUB, whereas CDKA was stably expressed, consistent with the results of qRT-PCR. CONCLUSIONS: CDKA and GAPDH are the best choice for gene and protein expression analysis than the other candidate reference genes under EhV infection conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The stable internal control genes identified in this work will help to improve the accuracy and reliability of gene expression analysis and gain insight into complex E. huxleyi-EhV interaction regulatory networks.

Retraction notice: Effect of educational interventions on health in childhood: a meta-analysis of randomized controlled trials [Public Health Volume 164, November 2018, Pages 134-147].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The article is a duplicate of a paper that has already been published in Medicine, 97 (2018) e11849 https://doi.org/10.1097/MD.0000000000011849. Redundant publications overweigh the relative importance of published findings and distort the academic record of the authors. One of the conditions of submission of a paper for publication is therefore that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

[The diagnostic performance of galactomannan detection in invasive pulmonary aspergillosis with severe and critically ill influenza].

Objective: To analyze the diagnostic performance of serum and bronchoalveolar lavage fluid (BALF) galactomannan (GM) test in invasive pulmonary aspergillosis(IPA) with severe and critically ill influenza. Methods: A retrospective study was performed for 157 patients with severe and critically ill influenza admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to April 2019.Clinical characteristics and serum and BALF GM values were collected. The patients were divided into an IPA group (n=18) and a non-IPA group (n=139). The definition of IPA modified from AspICU algorithm taken as the gold standard (The corresponding clinical manifestations, imaging manifestations and microbiological diagnostic criteria should be met simultaneously), the performance of serum and BALF GM test and their combination to IPA with influenza were analyzed respectively and receiver operating characteristic curve (ROC) was drawn. Results: A total of 157 cases were enrolled, 95 were critically ill, and the mortality of IPA with influenza was 55.6%(10/18). The APACHE Ⅱ score, PSI score, urea nitrogen, influenza severity (Percentage of critically ill influenza) and invasive ventilator in IPA group were (16±6), (110±31), 10.7 (8.4, 17.8) mmol/L, 88.9% and 66.7%, respectively, which were significantly higher than those in non-IPA group [(10±5), (83±30), 5.2 (3.6, 7.6) mmol/L, 56.8% and 24.5%, P<0.05]. All patients received serum GM test and 32 patients performed BALF GM test at the same time. When the cut-off valve of serum GM test was 0.5 µg/L, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 66.7% (12/18), 95.0% (132/139), 63.2% (12/19) and 95.7% (132/138) respectively. When the cut-off value of BALF GM test was 1.0 µg/L, the sensitivity, specificity, PPV and NPV were 80%(8/10),86.4%(19/22),72.7%(8/11)and 90.5%(19/21)respectively. The BALF GM cut-off value of 0.88 µg/L showed the highest diagnostic efficacy for IPA, for which the sensitivity and specificity were 90%(9/10) and 86.4%(19/22). The areas under the ROC curve of serum GM, BALF GM, and the combination of them were 0.81, 0.85, and 0.94 respectively. The difference was statistically significant (P<0.05) and the combined diagnosis efficiency was higher. Conclusions: Critically ill influenza patients should be alert for IPA. The sensitivity of serum GM test in the diagnosis of IPA with influenza was low, while the NPV was high. The optimum BALF GM cut-off value was 0.88 µg/L. The combination with BALF and serum GM test can improve the diagnostic performance.

[Analysis of PARP inhibitors induced anemia in advanced and relapsed epithelial ovarian cancer].

Objective: To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC). Methods: Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed. Results: (1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions: One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

Intrinsic Mechanism for Anisotropic Magnetoresistance and Experimental Confirmation in Co_{x}Fe_{1-x} Single-Crystal Films.

Using first-principles transport calculations, we predict that the anisotropic magnetoresistance (AMR) of single-crystal Co_{x}Fe_{1-x} alloys is strongly dependent on the current orientation and alloy concentration. An intrinsic mechanism for AMR is found to arise from the band crossing due to magnetization-dependent symmetry protection. These special k points can be shifted towards or away from the Fermi energy by varying the alloy composition and hence the exchange splitting, thus allowing AMR tunability. The prediction is confirmed by delicate transport measurements, which further reveal a reciprocal relationship of the longitudinal and transverse resistivities along different crystal axes.

Investigation of Streptococcus agalactiae using pcsB-based LAMP in milk, tilapia and vaginal swabs in Haikou, China.

AIMS: To develop a pcsB-based Loop-mediated isothermal amplification (LAMP) method for the detection of Streptococcus agalactiae (GBS) in milk, tilapia and vaginal swabs. METHODS AND RESULTS: The sensitivity of the LAMP method using real-time turbidity monitoring was 1 pg of template within 1 h at 64°C, 100-fold higher than conventional PCR. The sensitivity of visual detection dropped an order of magnitude using SYBR Green I or hydroxynaphthol blue. The validity of the visual LAMP assay was assessed by the detection of GBS in 180 vaginal swabs from one hospital, 14 brain tissues samples of diseased tilapias from two fishponds and fresh milk of 67 dairy cattle from one farm. In total, 17 samples (4 vaginal swabs, 13 tilapia brain tissues but no milk sample) tested positive for GBS. Subsequent bacterial identification confirmed the specificity and reliability of the LAMP method. Molecular serotyping and multilocus sequence typing demonstrated that all 13 tilapia GBS isolates were identical (serotype Ia, ST7), whereas the four human GBS isolates were more diverse and could be classified into two serotypes (Ia, III) and four sequence types (ST19, ST23, ST24, ST862). Virulence gene testing showed that only the bac, rib and lmb genes were not present in all isolates. Antimicrobial susceptibility profiles of the isolates were basically consistent with their genotypes, except for sulphonamide and fluoroquinolone. CONCLUSIONS: We developed a reliable pcsB-based LAMP assay for GBS detection. Our results demonstrated that the prevalence of GBS was 92·9% among diseased tilapia, 2·2% among female patients and 0% on a dairy farm in Hainan. SIGNIFICANCE AND IMPACT OF THE STUDY: The pcsB-based LAMP method is suitable for GBS detection and contains great potential of application in dairy industry, aquiculture and clinical.

CircABCB10 silencing inhibits the cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis in rectal cancer.

Circular ATP binding cassette subfamily B member 10 (circABCB10) has been identified to have oncological functions in several tumors. However, the roles of circABCB10 in rectal cancer remain unknown. The expression of circABCB10, microRNA (miR)-326 and C-C motif chemokine ligand 5 (CCL5), and apoptosis related-protein was detected using quantitative real-time polymerase chain reaction or western blot, respectively. Cell survival or apoptosis was measured using cell counting kit-8 assay or flow cytometry. The accumulations of intracellular lipid reactive oxygen species (ROS) and Fe2+ were analyzed using C11-BODIP dye or iron kit assay, respectively. In vivo experiments were conducted using the murine xenograft model. The interaction between miR-326 and circABCB10 or CCL5 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircABCB10 and CCL5 were upregulated but miR-326 was downregulated in rectal cancer. The knockdown of circABCB10 promoted rectal cancer cell ferroptosis and apoptosis in vitro as well as inhibited tumor growth in vivo. miR-326 was a target of circABCB10, and the miR-326 inhibition could partially attenuate circABCB10 deletion-induced cell ferroptosis and apoptosis. miR-326 directly interacted with CCL5, and the miR-326 inhibition suppressed cell ferroptosis and apoptosis by targeting CCL5. Besides, we observed that miR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy.

Immediate early response protein 2 promotes the migration and invasion of hepatocellular carcinoma cells via regulating the activity of Rho GTPases.

Human immediate early response 2 (IER2) has been implicated in tumor cell motility and metastasis; however, the underlying mechanisms in hepatocellular carcinoma (HCC) metastasis remain to be clarified. In this study, we demonstrate that dysregulation of IER2 was shown in HCC clinical samples, and IER2 expression resulted in the promotion of cell migration and invasion in vitro, and HCC tumor growth and pulmonary metastasis in vivo. Moreover, we showed that IER2 expression altered assembly of the actin cytoskeleton rearrangement. Furthermore, MAPK and PI3K/Akt signaling pathways induced by IER2 were confirmed to be probably involved in regulating the activity of Rho GTPases, such as RhoA, Rac1 and Cdc42. Collectively, our results indicated a significant role of IER2 in the HCC cell motility and metastasis through MAPK and PI3K/Akt signaling pathways to regulate the activity of Rho GTPases, thereby modulating actin cytoskeleton rearrangement, unveiling a novel mechanism of cell motility regulation induced by IER2.

Both Caspase and Calpain are Involved in Endoplasmic Reticulum-Targeted BNIP3-Induced Cell Death.

Bcl-2/E1B-19K-interacting protein 3 (BNIP3) is a member of the apoptotic B-cell lymphoma-2 family that regulates cell death. Although BNIP3 targeted normally to the mitochondrial outer membrane by its transmembrane domain was originally considered to be essential for its pro-apoptotic activity, accumulating evidence has shown that BNIP3 is localized to endoplasmic reticulum at physiological conditions and that forced expression of BNIP3 can initiate cell death via multiple pathways depending on the subcellular compartment it targets. Targeting BNIP3 to endoplasmic reticulum has been shown to participate in cell death during endoplasmic reticulum stress. However, the molecular events responsible for BNIP3-induced cell death in the endoplasmic reticulum remain poorly understood. In the present study, the transmembrane domain of BNIP3 was replaced with a segment of cytochrome b5 that targets BNIP3 into endoplasmic reticulum, which induced cell death as effectively as its wild-type molecule in the SW480 cell line (colon carcinoma). Furthermore, a pan-caspase inhibitor, z-VAD-fmk, and PD150606, a specific calpain inhibitor, both significantly suppressed the endoplasmic reticulum-targeted BNIP3-induced cell death. These results suggest that endoplasmic reticulum-targeted BNIP3 induced a mixed mode of cell death requiring both caspases and calpains.