bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a tool for reversed-phase protein microarrays (RPMA) and use in immunoproteomics of breast cancer
Authors: Keller K. , Boehm D. , Lebrecht A. , Schmidt M. , Koelbl H. , Grus F.
Published: August 2020

e22186

Background: Breast cancer is the most commonly diagnosed cancer type in women and one of the most frequent types of cancer which leads to death. It´s early detection is a key factor for successful treatment of patients. Besides, most of the current biomarkers are still lacking of specificity. In the past decade cancer immunogenicity has been described. A development of a new non-invasive method for the detection of humoral response to cancer would be of great benefit. Methods: The proteins from healthy breast tissue and carcinoma were extracted and separated via sodium dodecylsulfate polyacrylamide gel electrophoresis. The non-stained proteins were cut out of gel, digested with trypsin and spotted on nitrocellulose microarray slides. Each sub array was incubated either with different sera of breast cancer patient or with control sera and afterwards labelled with a cyanine 5-labelled human anti-immunoglobulin G antibody (IgG). Results: The extracted and digested protein fractions from both tissue types showed reproducible antibody profiles after the incubation with sera and labelling with anti-IgG antibody. The intensity of the detected signals varied within different protein fractions. Conclusions: This method provides a stable, simple and reproducible visualization of specific antibody profiles. Further upgrading of this method could facilitate a development of a fast, non-invasive and cost- efficient tool for immunoproteomics of cancer. Moreover, the following subsequent identification of the involved tumor associated antigens (TAA´s) is crucial for an understanding of their role in pathogenesis and cancer development, possibly leading to design of new cancer therapies.

No significant financial relationships to disclose.
Dual inhibition of aromatase and epidermal growth factor receptor in non-small cell lung cancer
Authors: Koutras A. , Kritikou I. , Giannopoulou E. , Dimitropoulos K. , Kalofonos H.
Published: August 2020

e22189

Background: Recent evidence suggests that estrogen signaling is important in the progression of cancers expressing estrogen receptors (ERs) and may also be involved in the pathogenesis of non-small cell lung cancer (NSCLC). Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In view of a possible functional interaction between the ER and the epidermal growth factor receptor (EGFR) pathways in NSCLC, we investigated the dual inhibition of aromatase and EGFR in NSCLC cell lines. Methods: In the current study we used exemestane, an irreversible steroidal aromatase inactivator, and erlotinib, an EGFR tyrosine kinase inhibitor. The in vitroexperiments were performed using H23 and A549, two NSCLC cell lines with low and high levels of aromatase, respectively. Cell proliferation was measured by MTT assay. Metalloproteinase (MMP) levels were detected by zymography and cell migration was determined by boyden chamber assay. EGFR protein levels detection was performed by immunofluorescense assay. Results: Exemestane and erlotinib inhibited H23 and A549 cell proliferation either alone or in combination, 48 hours after their application. However, the combination of exemestane and erlotinib was more effective than each agent alone, in H23 cells. Furthermore, exemestane decreased MMP-2 and MMP- 9 levels in H23 cells, whereas erlotinib did not. The combination of exemestane and erlotinib had the same effect on MMPs, as exemestane alone. The effect on cell migration was in line with the results in MMPs levels. In A549 cells, no changes in MMPs levels or cell migration were demonstrated. In addition, exemestane altered the location of EGFR protein in H23 cells, but not in A549 cells. Conclusions: Our findings suggest an antiproliferative effect of exemestane and erlotinib in both cell lines, as well as synergy for the combination in H23 cells. The activity of the combination in these cells with low levels of aromatase might involve an additional effect of exemestane on EGFR protein location. Erlotinib did not enhance the effect of exemestane on MMPs secretion and migration in H23 cells.

No significant financial relationships to disclose.
Effect of endotoxin on COX-2 dependent proliferation of NSCLC cells: Role of CD14, TLRs, and EGFR signaling
Authors: Grandel U. , Banat A. , Savai R. , Eul B. , Fink L. , Seeger W. , Grimminger F. , Sibelius U. , Hattar K.
Published: August 2020

e22190

Background: Bacterial infections are common in NSCLC and growing evidence indicates that inflammation is contributing to cancer growth. Against this background, we investigated the effect of the bacterial cell wall components LPS on the proliferation of the NSCLC cell line A549. Methods: Proliferation of A549 cells was quantified by MTS-assay. PGE2 production was analyzed by ELISA and COX-2 mRNA was quantified by RT-PCR. Results: Incubation of A549 cells with LPS induced a time- and dose-dependent proliferation of A549 cells. Pro-proliferative effects of endotoxin could be inhibited by neutralizing antibodies targeting CD14 and TLR4, but not by inhibition of TLR2. Interestingly, interference with COX-2 activity by the specific inhibitor NS-398 strongly attenuated the LPS-induced tumor cell proliferation. In parallel, large amounts of COX-2 dependent PGE2were released by LPS-stimulated A549 cells. Moreover, enhanced transcription of COX-2 specific mRNA was detected in LPS-stimulated A549 cells. Interestingly, EGFR signaling was obviously involved in LPS-induced tumor cell proliferation and PGE2 release, as both effects could be inhibited by the neutralizing EGFR-antibody cetuximab. Conclusions: We conclude that LPS induces COX-2 dependent proliferation of A549 cells in a CD14, TLR4, and EGFR dependant manner. These effects might contribute to pathogen induced tumor proliferation in NSCLC.

No significant financial relationships to disclose.
Demographic features and prognostic profiles of breast cancer patients presenting with nipple discharge in Chinese population
Authors: Yin W. , Di G. , Liu G. , Wu J. , Lu J. , Shen K. , Han Q. , Shen Z. , Shao Z.
Published: August 2020

e22204

Background: Breast cancer patients with nipple discharge (ND) may constitute a distinct clinical entity compared to those without ND, which has not been well elucidated in previous reports. We sought to analyze the demographic features and prognostic profiles of breast cancer patients presenting with nipple discharge in Chinese population. Methods: A total of 3234 patients, categorized as ND (2.47%) and non-nipple discharge (NND; 97.53%) according to different initial signs, were retrospectively analyzed. Survival curves were performed with Kaplan-Meier method and annual recurrence hazard was estimated by hazard function. Results: ND group tended to have smaller tumors and less axillary lymph node (ALN) involvement than NND group (P < 0.05). In the univariate analysis, we found significantly different recurrence-free survivals (RFS) between subgroups (P = 0.0182), with the rate of 77.78% for ND group and 72.46% for the other at the 11th year respectively. In Cox proportional hazards regression analysis, we found that tumor size (P < 0.001), ALN status (P < 0.001) were independent prognostic factors for RFS. To further evaluate whether prognostic effect of ND status remained unabated over time, the test for lack of proportionality was performed. However, it was statistically significant (global test, P = 0.039), which hinted at a demand for the employment of Cox non-proportional hazards regression in this analysis. In time dependent Cox model, ND status (P = 0.0495) as well as ERBB2 status (P = 0.017), tumor size (P < 0.001), ALN status (P < 0.001) were independent prognostic factors when ND and ERBB2 status were taken as time-varying covariates. Annual hazard rates for recurrence remained lower on ND group until approximately 4.5 years after surgery, while the situation was just the opposite thereafter. Conclusions: Our findings suggested that demographic features and prognostic profiles were quite different between breast cancers presenting with and without ND in Chinese population, which may indirectly uncover distinct biological behaviors and potentially enlighten novel therapeutic approaches for patients with different initial signs.

No significant financial relationships to disclose.
An immunochemical analysis of multidrug resistance gene product P170 glycoprotein in human breast cancer tissues
Authors: Michalaki V. , Gennatas S. , Karvouni E. , Kondi-Pafiti A. , Gennatas C.
Published: August 2020

e22206

Background: P-glycoprotein (gp170; encoded by the MDR1 gene (also known as PGY1) is a membrane protein capable of exporting a variety of anticancer drugs from cells. MDR1/gp170 expression has been studied in breast cancer, but the prevalence of this expression and its role in breast tumour drug resistance are unclear. To offer more effective and less toxic treatment, selecting therapies requires considering the patient and the clinical and molecular characteristics of the tumour. Our primary goal was to clarify the prevalence and clinical relevance of MDR1/gp170 expression in breast cancer patients in correlation with clinocopathologic features. Methods: In this study the expression of MDR1/gp170 protein has been investigated in a series of 40 human breast carcinomas. The immunoperoxidase antigen detection protocol, was employed using anti-p170 monoclonal antibodies (MoABs), (JSB 1 Monosan). Clinicopathologic findings, grade, and molecular markers (HER2, estrogen receptor (ER)alpha, ER beta, and progesterone receptor were also analyzed. Results: MoAB JSB-1 reacted strongly with the transmembranic antigen epitope. The proportion of breast tumours expressing MDR1/gp170 was 22% in Grade 1, 71% and 45.4% in Grade2 and Grade3 Itumors. There was no correlation with hormone receptor status, lymph node status and ΕΕR-2. Conclusions: The data of MDR-1 product expression by immunohistochemistry in breast cancer might suggest that an overexpression of this protein could constitute a hallmark of potential more aggressive phenotype for this type of neoplasia and a rapid method for pre-screening tumours for a constitutive multidrug resistance in order to orientate the cancer treatment. While the functional relevance of this expression remains to be established, it seems likely that MDR1/gp170 is an independent prognostic factor in breast tumours.

No significant financial relationships to disclose.
Survival associated with bone metastases and skeletal-related events in breast cancer patients: A population-based cohort study in Denmark (1999 - 2007)
Authors: Yong M. , Jensen A. Ø. , Jacobsen J. B. , Nørgaard M. , Fryzek J. P. , Sørensen H. T.
Published: August 2020

e22210

Background: Breast cancer (BrCa) is the most commonly diagnosed cancer for women in the industrialized world. Among women who present with metastatic BrCa, more than half will develop bone metastases. Bone metastases increase the risk for skeletal-related events (SREs) defined as radiation to bone, pathologic fractures, spinal cord compression, surgery to bone, or change in antineoplastic therapy to treat bone pain. These complications are associated with an unfavorable prognosis and have a major impact on patients' quality of life. However, data on survival of BrCa patients who experience SREs are lacking. We evaluated survival among BrCa patients without bone metastases, with bone metastases, and with both bone metastases and SREs. Methods: Using Denmark's National Registry of Patients (NRP) database, we conducted a retrospective cohort study in the North and Mid- Jutland Region. Patients with a diagnosis of BrCa from January 1, 1999 through December 31, 2007 were identified using the International Classification of Diseases, 10th Revision (ICD-10) codes C50.x. SREs after BrCa diagnosis were identified using the ICD-10 code C79.5. Cox proportional-hazards regression was used to estimate the mortality rate ratio (MRR), adjusting for age and comorbidity, to compare survival among three subgroups of BrCa patients: no bone metastases, bone metastases, and bone metastases with SREs. Results: We identified 9,474 BrCa patients from the NRP. Of these, 621 (7%) developed bone metastases and 267 (3%) developed both bone metastases and SREs during the study period. The 5-year mortality rates among BrCa patients without bone metastases, with bone metastases, and with bone metastases and SREs were 50.7 per 1,000 person-years (PYs), 469 per 1,000 PYs, and 712 per 1,000 PYs, respectively. Compared to BrCa patients without bone metastases, the adjusted MRRs among BrCa patients with bone metastases and patients with bone metastases and SREs were 11.6 [95% confidence interval (CI): 10.9 - 13.6] and 18.1 (95% CI: 15.5 - 21.0), respectively. Conclusions: Our results suggest that bone metastases and SREs have a major impact on the overall mortality of BrCa patients in Denmark.

[Table: see text]
Micro RNA expression to predict side effects of preoperative chemoradiotherapy in rectal cancer
Authors: Nakao T.
Published: August 2020

e22211

Background: Preoperative chemoradiotherapy (CRT) in lower rectal cancer is used to prevent from local recurrence and preserve anus by avoiding to rectal amputation. We have reported 17 micro DNAs and micro RNAs can predict effect of CRT in ASCO-GI 2009. In this study we aimed to predict side effect of CRT such as diarrhea using micro RNA2. present 16 micro RNA to predict side effect of CRT. Methods: Rectal cancer patients (n=22) who underwent preoperative CRT (40Gy radiotherapy combined with S- 1) were studied. S-1 is a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase and has potent radiosensitizing property. RNA harvested from biopsy specimens of rectal cancer before preoperative CRT was hybridized to miRNA microarrays (821 genes). Side effect of CRT was evaluated by NCI-CTC. Groups were classified as side effect group (grade 3 or over) or non side effect group (group 0, 1, 2), respectively. Results: Fifteen patients had well differentiated adenocarcinoma and 7 patients had poorly differentiated adenocarcinoma. Before CRT, 3 patients are stage I, 1 patient is stage IIA, 7 patients are stage IIIB, 8 patients are stage lllC, 3 patients are stage lV in TMN classification. After CRT, 14 patients had PR (RR 63.6%) in RECIST and 15 patient had down staging in TMN classification. Four patients had side effect. One patient had diarrhea and cytopenia, 2 patients had diarrhea, 1 patient had dermatitis. All of them were grade 3. Sixteen miRNAs(micro RNA23a, 27a, 142–3p, 142–5p, 155, 185, 196a, 221, 223, 224, 374a, 374b, 376a, 378, 424, 452) were significantly lower expressed in side effect group than no side effect group. Conclusions: Sixteen micro RNAs were down-regulated in side effect group. Therefore, profile of micro RNA expression may predict the side effect of CRT.

No significant financial relationships to disclose.
Occurrence of BRCA1–2 mutations and overall survival among breast cancer patients from Sardinia
Authors: Palmieri G. , Palomba G. , Loi A. , Uras A. , Budroni M. , Contu A. , Cossu A. , Farris A. , Crisponi L. , Monne M.
Published: August 2020

e22215

Background: Germline mutations in BRCA1-2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA1–2 mutations on prognosis and survival of breast cancer patients is still debated. In this study, we extensively investigated the prevalence and geographical distribution of BRCA1–2 mutations in the entire genetically-homogeneous Sardinian population as well as tried to clarify the influence of such mutations on breast cancer-specific survival. Methods: Among incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA1–2 mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan- Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. Results: A lower breast cancer-specific overall survival rate was observed in BRCA1–2 mutation-positive patients after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. The geographical distribution of BRCA1–2 mutations was related to specific three large areas of Sardinia: a) the northern area, linguistically different from the rest of the island (where a BRCA2–8765delAG mutation with founder effect was predominant); b) the central-eastern area, land of the ancient Sardinian population (where BRCA2 mutations are still largely more common thanBRCA1 mutations); and c) the south-western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). Conclusions: In Sardinian breast cancer population, the effects of BRCA1–2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA1–2 mutation carriers and non-carriers. Finally, we identified some probands' phenotypic features which may be predictive for the presence of BRCA1–2 germline mutations and should be therefore considered when counselling patients about undergoing genetic testing.

No significant financial relationships to disclose.
The correlation of thrombin-activated fibrinolysis inhibitor (TAFI) levels and clinicopathologic factors in advanced colorectal cancer patients
Authors: Salman T. , Bilici A. , Ustaalioglu B. O. , Seker M. , Sonmez B. , Gumus M. , Salepci T. , Yaylaci M. , Orcun A. , Mayadagli A.
Published: August 2020

e22217

Background: There are many ongoing researchs for novel prognostic factors in colorectal cancers. Increased thromboembolic events were associated with poor prognosis and survival in cancer patients. Thrombin-activated fibrinolysis inhibitor (TAFI), which has inhibitory effects on fibrinolysis, was proven to play a major role in hypercoagulopathy and was reported to reach high blood levels in cancer patients compared to those in the general population. Methods: TAFI levels were measured. The correlation between those levels and clinicopathologic features were analyzed in 82 patients with advanced stage colorectal cancer receiving treatment in our clinic. Results: Eighty-two patients were evaluated. Patients characteristics included 54 males (65.9%), 28 females (34.1%); median age 56.4 (range:24–76). The mean TAFI levels was 198,36±70,01 Ğer yazali and TAFI levels were found to be high in 70% of patients. High levels of TAFI were more common in rectum cancer patients compared with colon cancer patients. There was no significant correlation between TAFI levels and clinicopathologic factors, such as age, sex, body mass index, performance status, number of metastases, grade, vascular invasion, perineural invasion and CEA levels. The TAFI levels of patients receiving bevacizumab (202.1±66.6) were more higher than those no receiving (191,83±76,21), but this association was not statistically significant (p>0.05). Conclusions: Although the statistical analysis proved insignificant in our study, the effect of thromboembolic events on prognosis and survival is well established. Thus, large scale prospective studies are required to determine prognostic factors.

No significant financial relationships to disclose.
Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer
Authors: Kwong A. , Wong L. , Wong C. , Law F. , Tang E. , Chan W. , Ma E. S. , Ford J. M. , West D. W.
Published: August 2020

e22226

Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women.

No significant financial relationships to disclose.
Postsurgical drainage and the risk of breast cancer recurrence in Chinese breast cancer patients
Authors: Lin Y. , Yin W. , Zhou L. , Yan T. , Lu J. , Di G. , Wu J. , Shen K. , Shao Z.
Published: August 2020

e22234

Background: Clinical investigations suggest that while primary breast cancer surgical removal favorably modifiers the natural history of breast cancer. Postoperative drainage, a surgery-derived discharge after breast cancer surgery, reflecting some biological features of surgical stimulation, was assessed and explored its relationship with breast cancer recurrence in this study. Methods: A total of 1445 women undergoing surgery between Jan 1, 2000 and Dec31, 2002 in Cancer Hospital of Fudan University, Shanghai, China was retrospectively studied. Survival curves were performed with Kaplan-Meier method and the predictive value of postsurgical drainage was estimated using proportional Cox regression model. Conclusions: The larger drainage volume POD 1 is a useful marker, suggesting a greater stimulation to surgical treatment compared to the lower ones. Awareness of the relationship between early surgery-stimulated effects and harmful wound healing response might help to explore new strategies to block or deplete these harmful effects, resulting in improving patients' survival.

No significant financial relationships to disclose.
HIV/AIDS pandemic (AP) in Africa: Chronicle of a missed opportunity
Authors: Williams C. K.
Published: August 2020

e22235

Background: AP unlike HTLV-I associated diseases arrived late in parts of Africa, including Nigeria, where retroviral research was already ongoing in collaboration with the US National Cancer Institute (USNCI), thus providing unique preventive interventional opportunity. A World Health Organization sponsored study of the role of sexual behavior in retroviral transmission in Nigeria was performed 1985–86. Methods: Using an ELISA and an investigational Western blot (IWB) assay, a small survey of the seroprevalence rate (SPR%) of HTLV-I and HIV was conducted in 3 regions of the country among 5 population groups with differing sexual behaviors: normal blood donors (NBD), female commercial sex workers (FCSW), sexually transmitted diseases patients, and religious male/female celibates. 204 samples were re-tested with recombinant enhanced “Singapore” HIV-1/2 WB (SWB) in 1994, in view of earlier HIV-1 IWB negativity. All serological tests were done at USNCI. Results: HTLV-I SPR varied by region and lifestyle, highest in eastern region (ER) (p=0.0000095), FCSW of ER (p=0.0006), and frequency of male heterosexual activity (p=0.024). HIV-1 was undetectable by IWB, while SWB revealed 2/204 HIV-1+ for countrywide SPR: ∼1.0; Western NBD: 1/100 (1.0); Western/Northern NBD: 1/184 (0.54): non-high risk Nigerians: 2/237 (0.84); FCSW: 0/46; celibates: 0/71, adult general Nigerian population (AGNP): ∼0.5–1.0, and translating to (∼240–480)x103 HIV-1+ AGNP. Assuming 20 HIV-1+ = 1 case of AIDS death, SWB- determined SPR predicted (∼12–24)×103 AIDS deaths among 48×106 AGNP in 1985–86, ∼5 of (2.4- 4.8)×103 (<0.2%) of whom presented with clinical AIDS features (CAF) at Nigeria's premier health institution (NPHI). Conclusions: In 1985–86, when patients with CAF rarely presented at NPHI and HIV-1 SPR was ≤1.0 in AGNP and FCSW, Nigerian health authority was advised on AP risk, unlike Uganda where it arrived unanticipated. Reports of SPR of 7.7 and 60.0 in AGNP and FCSW in 1996–2000 contrast against contemporary Ugandan SPR (14.0 down to 6.1) and Senegalese (0.4 up to 0.9), probably resulting from varying knowledge gap and angst-related inertia, illustrating mixed fortunes of AP in Africa, transcontinental variation in AP control capability, and providing lessons for the management of future public health challenges.

No significant financial relationships to disclose.
ESPAC-3(v2): A multicenter, international, open-label, randomized controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma
Authors: Neoptolemos J. , Büchler M. , Stocken D. D. , Ghaneh P. , Smith D. , Bassi C. , Moore M. , Cunningham D. , Dervenis C. , Goldstein D. ,   The European Study Group for Pancreatic Cancer (ESPAC)
Published: August 2020

LBA4505

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

[Table: see text]
Relationships Between Vasomotor Symptoms and Mood in Midlife Urban Chinese Women: Observations in a Prospective Study
Authors: Tang Ruiyi , Luo Min , Li Jiayi , Peng Yajing , Wang Yuchen , Liu Bing , Liu Gaifen , Wang Yaping , Lin Shouqing , Chen Rong
Published: August 2020

Context

During the menopausal transition, there is a greater likelihood of the prevalence of various bothersome symptoms, including vasomotor symptoms (VMS) and mood symptoms.

Objective

To investigate the association among bothersome VMS and symptoms of anxiety and depression in Chinese women during perimenopause and early in menopause.

Design, Patients, Setting, and Interventions

This study included 430 midlife Chinese women who had experienced natural menopause and were followed up for 10 years. A structured questionnaire was provided annually, comprising the VMS Bother Score (range 1-8) from the Menopause-Specific Quality of Life questionnaire, the Hospital Anxiety and Depression Scale, and other physical and behavioral factors.

Results

Among the 430 women evaluated, 78.8% had experienced VMS during long-term follow-up. The overall level of VMS bother score was relatively low (1.92 ± 1.32). Both anxiety and depressive symptoms were significantly associated with VMS bother. After adjusting for potential covariates, the association between anxiety or depression symptoms and VMS bother remained highly significant. Menopausal stage, body mass index, general health, follicle-stimulating hormone, and estradiol were independent contributors to VMS. In time-lagged (1-year) models, VMS bother scores significantly predicted the risk of symptoms of both anxiety and depression the following year. In contrast, anxiety symptoms, rather than depressive symptoms, could predict VMS bother the following year.

Conclusion

The prevalence of VMS in our cohort was higher than has been previously reported; however, the overall level of bother was relatively low. This study demonstrated a strong relationship between VMS bother and mood symptoms in Chinese women progressing from perimenopause through natural menopause.
High-Fat Diet Alters LH Secretion and Pulse Frequency in Female Mice in an Estrous Cycle-Dependent Manner
Authors: Negrón Ariel L , Radovick Sally
Published: August 2020

Reproductive fitness in females is susceptible to obesogenic diets. Energy balance and reproduction are tightly regulated, in part, by hypothalamic neurons in the arcuate nucleus (ARC), and high-fat diet (HFD) can steadily increase estradiol levels in rodents. Estradiol regulates the reproductive axis via negative feedback mechanisms in ARC neurons by modulating pulsatile release of the gonadotropin luteinizing hormone (LH). However, it is unclear how the circulating estradiol milieu of adult females interacts with a state of high-caloric fat intake to alter LH pulse dynamics. Here, we used serial tail-tip blood sampling to measure pulsatile LH release at different estrous cycle stages in mice fed a HFD. Starting at 21 days of age, female C57BL/6J mice were freely fed with either regular chow diet (RD) or 60% kcal HFD for 12 weeks. Blood samples were collected once at diestrus, and then again at estrus. LH was measured in 10-minute intervals for 3 hours and analyzed for pulse frequency, amplitude, and mean and basal LH levels. Compared with RD-fed controls, mice fed HFD displayed significantly increased pulse frequency at diestrus, but not at estrus. HFD-fed mice also had lower mean and basal LH levels compared with RD-fed controls, but only during estrus. These data suggest that circulating estradiol can variably contribute to the impact that HFD has on LH pulsatile release and also provide insight into how obesity impacts women’s reproductive health when ovarian estradiol levels drastically change, such as during menopause or with hormone replacement therapy.
Role of the Sec22b–E-Syt complex in neurite growth and ramification
Authors: Gallo Alessandra , Danglot Lydia , Giordano Francesca , Hewlett Bailey , Binz Thomas , Vannier Christian , Galli Thierry
Published: August 2020

Axons and dendrites are long and often ramified neurites that need particularly intense plasma membrane (PM) expansion during the development of the nervous system. Neurite growth depends on non-fusogenic Sec22b–Stx1 SNARE complexes at endoplasmic reticulum (ER)–PM contacts. Here, we show that Sec22b interacts with members of the extended synaptotagmin (E-Syt) family of ER lipid transfer proteins (LTPs), and this interaction depends on the longin domain of Sec22b. Overexpression of E-Syts stabilizes Sec22b–Stx1 association, whereas silencing of E-Syts has the opposite effect. Overexpression of wild-type E-Syt2, but not mutants unable to transfer lipids or attach to the ER, increase the formation of axonal filopodia and ramification of neurites in developing neurons. This effect is inhibited by a clostridial neurotoxin cleaving Stx1, and expression of the Sec22b longin domain and a Sec22b mutant with an extended linker between the SNARE and transmembrane domains. We conclude that Sec22b–Stx1 ER–PM contact sites contribute to PM expansion by interacting with LTPs, such as E-Syts.

This article has an associated First Person interview with the first author of the paper.
Mitochondrial import, health and mtDNA copy number variability seen when using type II and type V CRISPR effectors
Authors: Antón Zuriñe , Mullally Grace , Ford Holly C. , van der Kamp Marc W. , Szczelkun Mark D. , Lane Jon D.
Published: August 2020

Current methodologies for targeting the mitochondrial genome for research and/or therapy development in mitochondrial diseases are restricted by practical limitations and technical inflexibility. A molecular toolbox for CRISPR-mediated mitochondrial genome editing is desirable, as this could enable targeting of mtDNA haplotypes using the precision and tuneability of CRISPR enzymes. Such ‘MitoCRISPR’ systems described to date lack reproducibility and independent corroboration. We have explored the requirements for MitoCRISPR in human cells by CRISPR nuclease engineering, including the use of alternative mitochondrial protein targeting sequences and smaller paralogues, and the application of guide (g)RNA modifications for mitochondrial import. We demonstrate varied mitochondrial targeting efficiencies and effects on mitochondrial dynamics/function of different CRISPR nucleases, with Lachnospiraceae bacterium ND2006 (Lb) Cas12a being better targeted and tolerated than Cas9 variants. We also provide evidence of Cas9 gRNA association with mitochondria in HeLa cells and isolated yeast mitochondria, even in the absence of a targeting RNA aptamer. Our data link mitochondrial-targeted LbCas12a/crRNA with increased mtDNA copy number dependent upon DNA binding and cleavage activity. We discuss reproducibility issues and the future steps necessary for MitoCRISPR.
Echolocating bats exhibit differential amplitude compensation for noise interference at a sub-call level
Authors: Lu Manman , Zhang Guimin , Luo Jinhong
Published: August 2020

Flexible vocal production control enables sound communication in both favorable and unfavorable conditions. The Lombard effect, which describes a rise in call amplitude with increasing ambient noise, is a widely exploited strategy by vertebrates to cope with interfering noise. In humans, the Lombard effect influences the lexical stress through differential amplitude modulation at a sub-call syllable level, which so far has not been documented in animals. Here, we bridge this knowledge gap with Hipposideros bats which produce echolocation calls consisting of two functionally well-defined units: the constant-frequency (CF) and frequency-modulated (FM) components. We show that ambient noise induced a strong, but differential, Lombard effect in the CF and FM components of the echolocation calls. We further report that the differential amplitude compensation occurred only in the spectrally overlapping noise conditions, suggesting a functional role in releasing masking. Lastly, we show that both species of bats exhibited a robust Lombard effect in the spectrally non-overlapping noise conditions, which contrast sharply with the existing evidence. Our data highlight echolocating bats as a potential mammalian model for understanding vocal production control.
Optimizing G6PD testing for Plasmodium vivax case management and beyond: why sex, counseling, and community engagement matter
Authors: Chu Cindy S , Bancone Germana , Kelley Maureen , Advani Nicole , Domingo Gonzalo J , Cutiongo-de la Paz Eva M , van der Merwe Nicole , Cohen Jessica , Gerth-Guyette Emily
Published: August 2020

Safe access to the most effective treatment options for Plasmodium vivax malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against P. vivax hypnozoites. Until recently, only qualitative tests were available in most settings. These can identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female). This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females—who, unlike males, can have a heterozygous genotype for G6PD. Increasing recognition of the need for radical cure of  P. vivax, first for patients’ health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of user-friendly, affordable, and accurate quantitative point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.
Depressive symptoms measured using the Edinburgh Postnatal Depression Scale in mothers and partners in the ALSPAC Study: A data note
Authors: Paul Elise , Pearson Rebecca M.
Published: August 2020

Depression is a leading cause of disability and is associated with a number of adverse offspring outcomes when it occurs in parents. Depression is present in men and women at different rates, and recent research suggests that symptom profiles between the sexes may differ. Longitudinal data are needed to answer remaining questions about the long-term course, gender differences, antecedents and outcomes of depression. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a large birth cohort study in England which administered one of the most commonly used depression instruments, the Edinburgh Postnatal Depression Scale (EPDS) at 11 timepoints in mothers and at 10 timepoints in their partners. In addition to repeated measurements of the EPDS, ALSPAC has a wealth of participant data on biological, social, demographic, and lifestyle factors. The purpose of this data note is to introduce potential users of the data to the characteristics of the EPDS in ALSPAC, as well as some key considerations when using the data.
Protocol: Leveraging a demographic and health surveillance system for Covid-19 Surveillance in rural KwaZulu-Natal
Authors: Siedner Mark J. , Harling Guy , Derache Anne , Smit Theresa , Khoza Thandeka , Gunda Resign , Mngomezulu Thobeka , Gareta Dickman , Majozi Nomathamsanqa , Ehlers Eugene , Dreyer Jaco , Nxumalo Siyabonga , Dayi Njabulo , Ording-Jesperson Gregory , Ngwenya Nothando , Wong Emily , Iwuji Collins , Shahmanesh Maryam , Seeley Janet , De Oliveira Tulio , Ndung'u Thumbi , Hanekom Willem , Herbst Kobus
Published: August 2020

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute’s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal; determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing; determining the impact of HIV and tuberculosis on Covid-19 susceptibility; and using collected data to support the local public-sector health response.

The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care – conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.
The experience of family caregivers caring for a patient with chronic disorders of consciousness: a qualitative content analysis
Authors: Imani-Goghary Zahra , Ghaljeh Mahnaz
Published: August 2020

Background:

Management of a patient with chronic disorders of consciousness is a long-term and stressful situation for family caregivers.

Aims:

The aim of this study was to describe the experiences of family caregivers of patients with chronic disorders of consciousness.

Methods:

Purposeful sampling was used, data were collected through semi-structured, in-depth interviews at participants' homes. Data were analysed using qualitative content analysis.

Findings:

Results indicated that family caregivers of patients with chronic disorders of consciousness face many difficulties in providing care to vegetative state (VS) and minimally conscious state (MCS) patients; they experience it as a challenging type of care, which influences their mental health.

Conclusion:

Family caregivers are faced with many challenges because of the high burden of care, round-the-clock concern, taking care of an alive but unresponsive patient without receiving enough support. They experience mental and inner turmoil because of social isolation and dealing with contradictory feelings in their daily life.
Nurses' early and ongoing encounters with the dying and the dead: a scoping review of the international literature
Authors: Jones Kerry , Draper Jan , Davies Alison
Published: August 2020

Background:

End-of-life care is high on policy and political agendas in the UK and internationally. Nurses are at the forefront of this, caring for dying patients, ‘managing’ the dead body, and dealing with the corporeal, emotional and relational dimensions of death. Little is known about nurses' prior or early professional experiences of and reactions to death, dying and the corpse and how these might influence practice.

Aims:

To appraise the international literature on nurses' early experiences of death, dying and the dead body, to better understand how these might influence subsequent practice, and how this might inform our teaching of death, dying and last offices.

Methods:

A scoping review was undertaken of peer-reviewed publications between, 2000 and 2019, which included nurses working in hospital, care homes and the community. Medline, PubMed, PsychINFO and CINAHL databases were searched and 23 papers meeting the inclusion criteria were read. Arksey and O'Malley's (2005) five-stage approach was adopted to scope the relevant international literature, using where relevant the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Selected papers were independently reviewed and subjected to thematic analysis, leading to the generation of five overarching themes.

Results:

The five themes were: different philosophies of care; relationships; knowledge; impact of death; and giving care. The studies came from diverse geographical locations across different settings and were primarily qualitative in design.

Conclusions:

Students and registered nurses are impacted both positively and negatively by their early encounters with death and dying. Good communication with patients, families and between professionals, understanding of what constitutes a ‘good’ death, and high-quality mentorship and support were of particular importance.
Expansion of axial dispersion in a photopolymer-based holographic lens
and its improvement for measuring displacement
Authors: Liu Yangyu , Liu Hongpeng , Wang Baohua , Wei Mingzhao , Li Li , Wang Weibo
Published: August 2020

Coaxial multiple holographic lenses as high-dispersion elements are
developed for a spectral confocal displacement measurement device.
Wavelength and coaxial spatial multiplexing methods are used to record
the holographic lens with two coaxial foci. The expansion of axial
spatial dispersion in photopolymer-based multiple holographic lenses
has been demonstrated and studied experimentally. The multiple
holographic lenses provide a larger spatial dispersion to improve the
characteristic parameters for measuring the displacement. Compared to
single holographic lenses, the maximum of axial dispersion wavelength
difference of the multiple lenses increases from 134.63 to 162.81 nm,
and the corresponding measurable range increases from 203 to 385 mm.
The axial spatial dispersion conforms to a typical exponential
function. The overall spatial position sensitivity of multiple
holographic lenses reaches 2.36 mm/nm. In addition, the multiple
lenses also decrease the lateral dispersion compared to the single
lenses. The multiple lenses  can efficiently reduce the transverse
measurement error. Finally, the displacement measurement result
confirms the improvement of measureable spatial range. The multiple
holographic lenses can accelerate the practical application of
holographic lens-based optical elements.
Investigation of photodarkening in tandem-pumped Yb-doped fibers
Authors: Park J. S. , Kim T. H. , Oh Y. J. , Park E. J. , Kim J. W. , Jeong Hoon
Published: August 2020

Investigation of photodarkening (PD) in Yb-doped fibers tandem-pumped at 1018 nm is reported. For a homemade Yb-doped aluminosilicate double-clad fiber (YADF), the transmitted power of a 633 nm probe beam is reduced by 2.4% over 2 hours for the tandem pumping configuration at 1018 nm, which is significantly smaller than 33.3% for a laser diode (LD) pumping at 976 nm. A tandem-pumped Yb fiber amplifier also shows a much smaller decrease in the amplified output power over time than a LD-pumped Yb fiber amplifier. Based on fluorescence spectra of the YADF, we can not only associate PD of the YADF to intrinsic oxygen deficiency centers or Tm3+ impurities but also confirm the impact of the excited Yb3+ ion density on PD. The benefits of the tandem pumping in a high-power Yb fiber laser system will be discussed.
Received signal strength assisted perspective-three-point algorithm for indoor visible light positioning
Authors: Bai Lin , Yang Yang , Feng Chunyan , Guo Caili
Published: August 2020

In this paper, a received signal strength assisted perspective-three-point positioning algorithm (R-P3P) is proposed for visible light positioning (VLP) systems. Due to the directional propagation of visible light, the orientations of light-emitting diodes (LEDs) and receivers can affect the positioning accuracy seriously. To circumvent this challenge, R-P3P is proposed to mitigate the limitation on LEDs’ and receiver’s orientation in VLP systems. The basic idea of R-P3P is to jointly utilize visual and strength information to estimate the receiver position using 3 LEDs regardless of the orientations of LEDs and receivers. Simulation results show that R-P3P can achieve positioning accuracy within 10 cm over 70% of an indoor area with low complexity.