bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractContextDuring the menopausal transition, there is a greater likelihood of the prevalence of various bothersome symptoms, including vasomotor symptoms (VMS) and mood symptoms.ObjectiveTo 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 InterventionsThis 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.ResultsAmong 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.ConclusionThe 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

Abstract
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

ABSTRACT
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

ABSTRACT
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.
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.
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.