The impact of menstruation persistence or recovery after chemotherapy on survival in young patients with hormone receptor negative breast cancer

Introduction: Hormone replacement therapy can diminish hormone depletion-related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Recovery of menstruation after chemotherapy-induced amenorrhea in young hormone receptor-negative BC patients however, is accepted. To determine the safety of this strategy, we investigated the effect of recovery of menstruation on disease-free survival (DFS) and overall survival (OS) in young hormone receptor-negative BC patients treated with (neo)adjuvant chemotherapy. Methods: We selected 636 patients from a single-center cohort with early stage hormone receptornegative BC and under the age of 50 years when treated with chemotherapy. Sufficient data on course of menstruation in medical records was retrospectively found for 397 patients, of whom 299 patients (75%) had a recovery of menstruation after chemotherapy. We used Cox proportional hazards models to estimate hazard ratios (HR) for the effect of recovery of menstruation on DFS and OS. Results: Patients with recovery of menstruation after chemotherapy less frequ

Improving plant drought tolerance and growth under water limitation through combinatorial engineering of signalling networks

Agriculture is by far the biggest water consumer on our planet, accounting for 70 per cent of all freshwater withdrawals. Climate change and a growing world population increase pressure on agriculture to use water more efficiently ('more crop per drop'). Water-use efficiency (WUE) and drought tolerance of crops are complex traits that are determined by many physiological processes whose interplay is not well understood. Here, we describe a combinatorial engineering approach to optimize signalling networks involved in the control of stress tolerance. Screening a large population of combinatorially transformed plant lines, we identified a combination of calcium-dependent protein kinase genes that confers enhanced drought stress tolerance and improved growth under water-limiting conditions. Targeted introduction of this gene combination into plants increased plant survival under drought and enhanced growth under water-limited conditions. Our work provides an efficient strategy for engineering complex signalling networks to improve plant performance under adverse environmental conditions, which does not depend on prior understanding of network function

The prevalence of the duodenal ulcer promoting gene (dupA) in Helicobacter pylori isolates varies by ethnic group and is not universally associated with disease development: a case-control study

<p>Abstract</p> <p>Background</p> <p>The putative <it>H. pylori </it>pathogenicity-associated factor <it>dupA </it>has been associated with IL-8 induction <it>in vitro</it>, and duodenal ulcer (DU) and gastric cancer (GC) development in certain populations, but this association is inconsistent between studies. We aimed to investigate <it>dupA </it>prevalence in clinical isolates from Sweden, Australia and from ethnic Chinese, Indians and Malays resident in Malaysia and Singapore and to examine the association with DU and GC. In addition we investigated the sequence diversity between isolates from these diverse groups and compared the level of IL-8 secretion in isolates possessing and lacking <it>dupA</it>.</p> <p>Methods</p> <p>PCR primers were designed to amplify over the C/T insertion denoting a continuous <it>dupA</it>. PCR products from 29 clinical isolates were sequenced and compared with sequences from three additional strains obtained from GenBank. Clinical isolates from 21 Malaysian patients (8 <it>dupA</it>-positive, 14 <it>dupA</it>-negative) were assessed for their ability to induce IL-8 in AGS cells <it>in vitro</it>. Statistical analysis was performed using Fisher's exact test.</p> <p>Results</p> <p>The prevalence of <it>dupA </it>in isolates from Swedish functional dyspepsia (FD) control patients (65%, 13/20) was higher and in isolates from Indian FD patients (7.1%, 3/42) was lower as compared with isolates from Chinese (28.9%, 13/49, P = 0.005, P = 0.025), Malay (35.7%, 5/14, P = 0.16, P = 0.018) and Australian (37.8%, 17/45, P = 0.060, P < 0.001) FD patients. <it>dupA </it>was associated with DU and GC development in Chinese with 62.5% (10/16) and 54.6% (12/22) of isolates possessing <it>dupA </it>respectively as compared with FD controls (28.9%) (P = 0.015, P = 0.032). No significant difference in prevalence of <it>dupA </it>between FD controls, DU (63.6%, 7/11) and GC (61.9%, 13/21) cases (P = 1.000) was observed in the Swedish population. Sequence analysis revealed a pairwise variation of 1.9% and all isolates possessed the C/T insertion. The average IL-8 induction was 1330 pg/mL for <it>dupA</it>-positive isolates and 1378 pg/mL for <it>dupA</it>-negative isolates.</p> <p>Conclusion</p> <p>Although <it>dupA </it>is highly conserved when present, we identified no consistent association between <it>dupA </it>and DU or GC development across the ethnic groups investigated, with the <it>dupA </it>prevalence in control groups varying significantly. Our results would suggest that in the clinical isolates investigated <it>dupA </it>is not associated with IL-8 induction <it>in vitro</it>.</p

Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking

The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin\u27s ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology

The impact of the COVID-19 pandemic on self-harm and suicidal behaviour: a living systematic review

Background: The COVID-19 pandemic has caused widespread morbidity and mortality as well as disruption to people’s lives and livelihoods around the world; this has occurred as a result of both infection with the virus itself and the health protection measures taken to curb its spread. There are concerns that rates of suicide, suicidal behaviours and self-harm may rise during and in the aftermath of the pandemic. Given the likely rapidly expanding research evidence base on the pandemic’s impact on rates of suicide, suicidal behaviours and self-harm and emerging evidence about how best to mitigate such effects, it is important that the best available knowledge is made readily available to policymakers, public health specialists and clinicians as soon as is possible. To facilitate this, we plan to undertake a living systematic review focusing on suicide prevention in relation to COVID-19.Method: Regular automated searches will feed into a web-based screening system which will also host the data extraction form for included articles. Our eligibility criteria are wide and include aspects of incidence and prevalence of suicidal behaviour, effects of exposures and effects of interventions in relation to the COVID-19 pandemic, with minimal restrictions on the types of study design to be included. The outcomes assessed will be death by suicide; self-harm or attempted suicide (including hospital attendance and/or admission for these reasons); and suicidal thoughts/ideation. There will be no restriction on study type, except for single case reports. There will be no restriction on language of publication. The review will be updated at three-monthly intervals if a sufficient volume of new evidence justifies doing so.Conclusions: Our living review will provide a regular synthesis of the most up-to-date research evidence to guide public health and clinical policy to mitigate the impact of COVID-19 on suicide.Protocol registration: PROSPERO CRD42020183326 01/05/202

K 1-6: an asymmetric planetary nebula with a binary central star

We present new imaging data and archival multiwavelength observations of the little studied emission nebula K 1-6 and its central star. Narrow-band images in H-alpha (+ [NII]) and [OIII] taken with the Faulkes Telescope North reveal a stratified, asymmetric, elliptical nebula surrounding a central star which has the colours of a late G- or early K-type subgiant or giant. GALEX ultraviolet images reveal a very hot subdwarf or white dwarf coincident in position with this star. The cooler, optically dominant star is strongly variable with a period of 21.312 +/- 0.008 days, and is possibly a high amplitude member of the RS CVn class, although an FK Com classification is also possible. Archival ROSAT data provide good evidence that the cool star has an active corona. We conclude that K 1-6 is most likely an old bona fide planetary nebula at a distance of ~1.0 kpc, interacting with the interstellar medium, and containing a binary or ternary central star. The observations and data analyses reported in this paper were conducted in conjunction with Year 11 high school students as part of an Australian Research Council Linkage Grant science education project, denoted Space To Grow, conducted jointly by professional astronomers, educational researchers, teachers, and high-school students.Comment: 13 pages, 5 figures, accepted by the Publications of the Astronomical Society of Australia (PASA

Data extraction methods for systematic review (semi)automation: Update of a living systematic review [version 2; peer review: 3 approved]

Background: The reliable and usable (semi)automation of data extraction can support the field of systematic review by reducing the workload required to gather information about the conduct and results of the included studies. This living systematic review examines published approaches for data extraction from reports of clinical studies. Methods: We systematically and continually search PubMed, ACL Anthology, arXiv, OpenAlex via EPPI-Reviewer, and the dblp computer science bibliography. Full text screening and data extraction are conducted within an open-source living systematic review application created for the purpose of this review. This living review update includes publications up to December 2022 and OpenAlex content up to March 2023. Results: 76 publications are included in this review. Of these, 64 (84%) of the publications addressed extraction of data from abstracts, while 19 (25%) used full texts. A total of 71 (93%) publications developed classifiers for randomised controlled trials. Over 30 entities were extracted, with PICOs (population, intervention, comparator, outcome) being the most frequently extracted. Data are available from 25 (33%), and code from 30 (39%) publications. Six (8%) implemented publicly available tools Conclusions: This living systematic review presents an overview of (semi)automated data-extraction literature of interest to different types of literature review. We identified a broad evidence base of publications describing data extraction for interventional reviews and a small number of publications extracting epidemiological or diagnostic accuracy data. Between review updates, trends for sharing data and code increased strongly: in the base-review, data and code were available for 13 and 19% respectively, these numbers increased to 78 and 87% within the 23 new publications. Compared with the base-review, we observed another research trend, away from straightforward data extraction and towards additionally extracting relations between entities or automatic text summarisation. With this living review we aim to review the literature continually