bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraperitoneal paclitaxel combined with FOLFOX/CAPOX plus bevacizumab for colorectal cancer with peritoneal carcinomatosis (the iPac-02 trial): study protocol of a single arm, multicenter, phase 2 study
Authors: Murono Koji , Yokoyama Yuichiro , Nozawa Hiroaki , Sasaki Kazuhito , Emoto Shigenobu , Matsuzaki Hiroyuki , Kashiwabara Kosuke , Ishigami Hironori , Gohda Yoshimasa , Yamaguchi Hironori , Kitayama Joji , Ishihara Soichiro
Published: June 2023

Background

The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial.

Methods

This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110).

Results

We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8–12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies.

Conclusion

Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.
Quality of life in benign colorectal disease—a review of the assessment with the Gastrointestinal Quality of Life Index (GIQLI)
Authors: Fuchs Karl-Hermann , Musial Frauke , Retzbach Laura , Hann Alexander , Meining Alexander
Published: June 2023

Background and purpose

The Gastrointestinal Quality of Life Index (GIQLI) is an instrument for the assessment of quality of life (QOL) in diseases of the upper and lower GI tract, which is validated in several languages around the world. The purpose of this literature review is the assessment of the GIQLI in patients with benign colorectal diseases. Reports on GIQLI data are collected from several institutions, countries, and different cultures which allows for comparisons, which are lacking in literature.

Methods

The GIQL Index uses 36 items around 5 dimensions (gastrointestinal symptoms (19 items), emotional dimension (5 items), physical dimension (7 items), social dimension (4 items), and therapeutic influences (1 item). The literature search was performed on the GIQLI and colorectal disease, using reports in PubMed. Data are presented descriptively as GIQL Index points as well as a reduction from 100% maximum possible index points (max 144 index points = highest quality of life).

Results

The GIQLI was found in 122 reports concerning benign colorectal diseases, of which 27 were finally selected for detailed analysis. From these 27 studies, information on 5664 patients (4046 female versus 1178 male) was recorded and summarized. The median age was 52 years (range 29–74.7). The median GIQLI of all studies concerning benign colorectal disease was 88 index points (range 56.2–113). Benign colorectal disease causes a severe reduction in QOL for patients down to 61% of the maximum.

Conclusions

Benign colorectal diseases cause substantial reductions in the patient’s QOL, well documented by GIQLI, which allows a comparison QOL with other published cohorts.
Intracoronary physiology-guided percutaneous coronary intervention in patients with diabetes
Authors: Scarsini Roberto , Tebaldi Matteo , Rubino Francesca , Sgreva Sara , Vescovo Giovanni , Barbierato Marco , Vicerè Andrea , Galante Domenico , Mammone Concetta , Lunardi Mattia , Tavella Domenico , Pesarini Gabriele , Campo Gianluca , Leone Antonio Maria , Ribichini Flavio Luciano
Published: June 2023

Objective

The risk of vessel-oriented cardiac adverse events (VOCE) in patients with diabetes mellitus (DM) undergoing intracoronary physiology-guided coronary revascularization is poorly defined. The purpose of this work is to evaluate the risk of VOCE in patients with and without DM in whom percutaneous coronary intervention (PCI) was performed or deferred based on pressure-wire functional assessment.

Methods

This is a retrospective analysis of a multicenter registry of patients evaluated with fractional flow reserve (FFR) and/or non-hyperaemic pressure ratio (NHPR). Primary endpoint was a composite of VOCE including cardiac death, vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR).

Results

A large cohort of 2828 patients with 3353 coronary lesions was analysed to assess the risk of VOCE at long-term follow-up (23 [14–36] months). Non-insulin-dependent-DM (NIDDM) was not associated with the primary endpoint in the overall cohort (adjusted Hazard Ratio [aHR] 1.18, 95% CI 0.87–1.59, P = 0.276) or in patients with coronary lesions treated with PCI (aHR = 1.30, 95% CI 0.78–2.16, P = 0.314). Conversely, insulin-dependent diabetes mellitus (IDDM) demonstrated an increased risk of VOCE in the overall cohort (aHR 1.76, 95% CI 1.07–2.91, P = 0.027), but not in coronary lesions undergoing PCI (aHR 1.26, 95% CI 0.50–3.16, P = 0.621). Importantly, in coronary lesions deferred after functional assessment IDDM (aHR 2.77, 95% CI 1.11–6.93, P = 0.029) but not NIDDM (aHR = 0.94, 95% CI 0.61–1.44, P = 0.776) was significantly associated with the risk of VOCE. IDDM caused a significant effect modification of FFR-based risk stratification (P for interaction < 0.001).

Conclusion

Overall, DM was not associated with an increased risk of VOCE in patients undergoing physiology-guided coronary revascularization. However, IDDM represents a phenotype at high risk of VOCE.

Graphical abstract
An early system A-type scheme for Saturn from Babylon
Authors: Steele John , de Jong Teije
Published: June 2023

In this paper we publish three fragments of a cuneiform tablet that, when complete, contained the dates and zodiacal positions of Saturn’s synodic phenomena for roughly 60 years. The text is unique in containing comparisons of computed data with observations. Through an analysis of the preserved data we propose that the dates and positions were computed by an otherwise unknown two-zone System A-type scheme and show that the computed data in the tablet can be dated to the fourth century BC. This early date and the comparisons with observations suggest that the text was produced during the period of active development of the planetary systems.
Tracking between cardiovascular-related measures at 4 and 8 years of age in the INMA-Asturias cohort
Authors: Fernández-Iglesias Rocío , Martinez-Camblor Pablo , Fernández-Somoano Ana , Rodríguez-Dehli Cristina , Venta-Obaya Rafael , Karagas Margaret R. , Tardón Adonina , Riaño-Galán Isolina
Published: June 2023

Identifying cardiovascular-related measures that track from early childhood into later ages may help inform early prevention targets for cardiovascular disease. In this study, the tracking of triglycerides (TG), high-density cholesterol (HDL-c), atherogenic coefficient (AC), waist circumference to height ratio (WC/Height), mean arterial pressure (MAP), and homeostatic model assessment of insulin resistance (HOMA-IR) was examined in the INMA-Asturias cohort between 4 and 8 years of age. The analysis was conducted in 307 children who participated in the INMA-Asturias cohort (Spain) at 4 and at 8 years of age. Quantile regression models were used to evaluate tracking between measures at both ages, with each measure at 8 years as the dependent variable and the rank transformation of the same measure at 4 years as the independent variable. We found a positive association between HDL-c rank at 4 years and higher quantiles of the HDL-c distribution at 8 years, with an increase of 2.93 mg/dL (95% CI: 1.98, 3.87) per decile in the 0.9 quantile. A positive association was also found for WC/Height, with an increase of 0.008 (95% CI: 0.004, 0.012) per decile in the 0.9 quantile. We observed that tracking for AC increased in the higher quantiles of the distribution at 8 years, with an increase of 0.11 (95% CI: 0.09, 0.14) in the 0.6 quantile compared to an effect of 0.15 (95% CI: 0.09, 0.21) in the 0.9 quantile.

  Conclusions: Adult markers of dyslipidemia and central obesity tracked between ages 4 and 8 years. For AC, tracking increased in the higher quantiles of the distribution.

What is Known:• Atherosclerosis begins in early life, so preventive efforts that start in childhood may delay progression to clinical disease. Determine what cardiovascular risk factors track into time since childhood bring the opportunity to identified those subjects at risk for later cardiovascular disease.• The study of risk factors in health populations and, particularly in children, copes with not clear and/or controversial thresholds definition. This makes it challenging to study tracking in pediatric ages.

What is New:• Quantile regression is a useful tool for assessing the tracking of risk factors for which there are no clinically meaningful thresholds. The increasing trend observed in the tracking of dyslipidemia suggests the possible difficulty that children with abnormal values at 4 years of age might have in normalizing them in future years.• The findings of this article may help to determine which cardiovascular-related measures could be screened and followed-up in children.
Psychosocial effects of the corona pandemic on people with cancer: a qualitative study
Authors: Hoppe Catalina , Büntzel Jens , Paradies Kerstin , Rösler Marie , Hübner Jutta ,   Working Group Prevention and Integrative Oncology of the German Cancer Society
Published: June 2023

Introduction

The Corona pandemic caused far-reaching changes since 2020. We wanted to find out which factors determined the psycho-social well-being of cancer patients during the pandemic.

Methods

From May to July 2021, structured interviews were conducted concerning lockdown, social limitations, the virus itself, the treatment situation, and opportunities.

Results

Twenty people took part in the study (doctors, psychologists, nurses, social workers, patients). One of the most important aspects was the ban on visits. Others were the fear of infection and the possibility of vaccination. Wearing a mask seem to have been worse for the experts. Conflicts in families about the “right” behavior to protect yourself from infection have been a stressful issue for patients, just as the lack of balance and recreation in free time.

Conclusion

Patients in the third wave of corona have become accustomed to the rules. Especially loneliness and the organization of time at home are psycho-social stress factors.
Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma
Authors: Wang Danwen , Deng Zhao , Lu Mengxin , Deng Kai , Li Zhiqiang , Zhou Fenfang
Published: June 2023

Background

Patients with clear cell renal cell carcinoma (ccRCC), which is the most commonly diagnosed subtype of renal cell carcinoma, are at risk of tumor metastasis and recrudescence. Previous research has shown that oxidative stress can induce tumorigenesis in many cancers and can be a target of cancer treatment. Despite these findings, little progress has been made understanding in the association of oxidative stress-related genes (OSRGs) with ccRCC.

Methods

In vitro experiments were conducted with MTT survival assays, qRT‒PCR, apoptosis assays, cell cycle assays, ROS assays, and IHC staining.

Results

In our study, 12 differentially expressed oxidative stress-related genes (DEOSGs) and related transcription factors (TFs) that are relevant to overall survival (OS) were screened, and their mutual regulatory networks were constructed with data from the TCGA database. Moreover, we constructed a risk model of these OSRGs and performed clinical prognostic analysis and validation. Next, we performed protein–protein interaction (PPI) network analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of MELK, PYCR1, and PML. A tissue microarray also verified the high expression of MELK and PYCR1 in ccRCC. Finally, in vitro cellular experiments demonstrated that knockdown of MELK or PYCR1 significantly inhibited ccRCC cell proliferation by causing cell apoptosis and inducing cell cycle arrest in the G1 phase. Intracellular ROS levels were elevated after these two genes were knocked down.

Conclusion

Our results revealed the potential DEORGs to be used in ccRCC prognostic prediction and identified two biomarkers, named PYCR1 and MELK, which regulated the proliferation of ccRCC cells by affecting ROS levels. Furthermore, PYCR1 and MELK could be promising targets for predicting the progression and prognosis of ccRCC, thereby serving as new targets for medical treatments.
How ecological and evolutionary theory expanded the ‘ideal weed’ concept
Authors: Lau Jennifer A. , Funk Jennifer L.
Published: June 2023

Since Baker’s attempt to characterize the ‘ideal weed’ over 50 years ago, ecologists have sought to identify features of species that predict invasiveness. Several of Baker’s ‘ideal weed’ traits are well studied, and we now understand that many traits can facilitate different components of the invasion process, such as dispersal traits promoting transport or selfing enabling establishment. However, the effects of traits on invasion are context dependent. The traits promoting invasion in one community or at one invasion stage may inhibit invasion of other communities or success at other invasion stages, and the benefits of any given trait may depend on the other traits possessed by the species. Furthermore, variation in traits among populations or species is the result of evolution. Accordingly, evolution both prior to and after invasion may determine invasion outcomes. Here, we review how our understanding of the ecology and evolution of traits in invasive plants has developed since Baker’s original efforts, resulting from empirical studies and the emergence of new frameworks and ideas such as community assembly theory, functional ecology, and rapid adaptation. Looking forward, we consider how trait-based approaches might inform our understanding of less-explored aspects of invasion biology ranging from invasive species responses to climate change to coevolution of invaded communities.
Bedeutung großskaliger Rückbaumaßnahmen für die Minimierung der Sohleintiefung und des erforderlichen Geschiebeeintrags sowie zur Verbesserung der Morphodynamik und Ökologie an der Grenzmur
Authors: Klösch Mario , Tritthart Michael , Beikircher Ulrich , Dunst Roman , Eder Markus , Senfter Stephan , Habersack Helmut
Published: June 2023

Die Einengung und Begradigung des Flusslaufs der Mur entlang der Staatsgrenze zwischen Österreich und Slowenien (Grenzmur) erhöhten den Geschiebetransport, während Unterbrechungen des Sedimentkontinuums im Einzugsgebiet die Geschiebenachfuhr verringerten. Diese Rahmenbedingungen führten zu gravierenden morphologischen Veränderungen und damit einhergehenden ökologischen Beeinträchtigungen und technischen Problemen. Durch die Sohleintiefung droht zudem ein gänzlicher Verlust des geringmächtigen Kiesbetts und ein Sohldurchschlag in Sedimente des Tertiärs. Gleichzeitig ist die Grenzmur in einen großen zusammenhängenden Auwald eingebettet und flussabwärts ohne Kontinuumsunterbrechung mit der Drau und der Donau verbunden, sodass dieser Abschnitt über ein großes ökologisches Potenzial verfügt. Jedoch zeigten bisherige Maßnahmen nicht die erhoffte, längerfristige sohlstabilisierende Wirkung.

Im Rahmen des EU-Interreg-SI-AT-Projekts goMURra wurde ein neuer Managementplan erstellt. Als Ziele wurden ein dynamisches Gleichgewicht des Sedimenthaushalts, eine verbesserte Grundwassersituation, ein reduziertes Hochwasserrisiko und eine ökologische Verbesserung der Fluss- und Auenlandschaft definiert. Ziel der vorliegenden Studie war die Entwicklung entsprechender Maßnahmen.

Zunächst wurde anhand vereinfachender Werkzeuge und anhand historischer Karten der Raumbedarf für eine natürlichere Morphologie der Grenzmur abgeschätzt. Danach wurden unter Berücksichtigung der Raumwiderstände drei Maßnahmentypen entwickelt. Zugrunde lag eine Hypothese, wonach der Geschiebebedarf zur Stabilisierung der Sohllage mit Zunahme der Breite und Sinuosität abnimmt. Numerische Simulationen der Hydrodynamik und des Sedimenttransports sowie Modellversuche dienten der eingehenden Prüfung der Maßnahmentypen.

Die Modellläufe bestätigten die Verringerung der Geschiebetransportkapazität in den entwickelten Maßnahmentypen mit einer Reduktion von bis zu 56 %. Durch die Bereitstellung von mehr Platz für die Grenzmur würden die Kosten für eine dringend benötigte Geschiebezugabe gesenkt, während der ökologische Wert – am deutlichsten beim größten Maßnahmentyp – steigen würde.
On the Bahri–Lions conjecture for elliptic equations with non-symmetric nonlinearities
Authors: Molle Riccardo , Passaseo Donato
Published: June 2023

We prove the existence of infinitely many solutions for a class of elliptic Dirichlet problems with non-symmetric nonlinearities. In particular, in suitable domains of $${\mathbb {R}}^n$$

R

n

with $$n\ge 3$$

n
≥
3

, this result gives a positive answer to a well known conjecture formulated by A. Bahri and P.L. Lions. The proof is based on a minimization method which does not require the use of techniques of deformation from the symmetry. This method allows us to piece together solutions of Dirichlet problems in suitable subdomains, so we obtain infinitely many nodal solutions with a prescribed nodal structure.
Coexisiting type 1 diabetes and celiac disease is associated with lower Hba1c when compared to type 1 diabetes alone: data from the Australasian Diabetes Data Network (ADDN) registry
Authors: James Steven , Perry Lin , Lowe Julia , Donaghue Kim C. , Pham-Short Anna , Craig Maria E. ,   the ADDN Study Group, Ambler Geoff , Anderson Kym , Andrikopoulos Sof , Batch Jenny , Brown Justin , Cameron Fergus , Colman Peter G. , Conwell Louise , Cotterill Andrew , Couper Jennifer , Davis Elizabeth , de Bock Martin , Fairchild Jan , Fegan Gerry , Fourlanos Spiros , Glastras Sarah , Goss Peter , Gray Leonie , Hamblin Peter Shane , Hofman Paul , Holmes-Walker Dianne Jane , Huynh Tony , Isaacs Sonia , Jefferies Craig , Johnson Stephanie , Jones Tim , Kao Jeff , King Bruce R. , Lafferty Antony , Martin Michelle , McCrossin Robert , Neville Kris , Pascoe Mark , Paul Ryan , Peña Alexia , Phillips Liza , Price Darrell , Rodda Christine , Simmons David , Sinnott Richard , Smart Carmel , Stone Monique , Stranks Steve , Tham Elaine , Waddell Barbara , Ward Glenn , Wheeler Ben , Woodhead Helen , Zimmermann Anthony
Published: June 2023

Aim

To compare HbA1c and clinical outcomes in adolescents and young adults with type 1 diabetes (T1D), with or without celiac disease (CD).

Methods

Longitudinal data were extracted from ADDN, a prospective clinical diabetes registry. Inclusion criteria were T1D (with or without CD), ≥ 1 HbA1c measurement, age 16–25 years and diabetes duration ≥ 1 year at last measurement. Multivariable Generalised Estimated Equation models were used for longitudinal analysis of variables associated with HbA1c.

Results

Across all measurements, those with coexisting T1D and CD had lower HbA1c when compared to those with T1D alone (8.5 ± 1.5% (69.4 ± 16.8 mmol/mol) vs. 8.7 ± 1.8% (71.4 ± 19.8 mmol/mol); p < 0.001); lower HbA1c was associated with shorter diabetes duration (B = − 0.06; 95% CI − 0.07 to − 0.05; p < 0.001), male sex (B = − 0.24; − 0.36 to − 0.11; p < 0.001), insulin pump therapy use (B = − 0.46; − 0.58 to − 0.34; p < 0.001), coexistence of T1D and CD (B = − 0.28; − 0.48 to − 0.07; p = 0.01), blood pressure (B = − 0.16; − 0.23 to − 0.09; p < 0.001) and body mass index (B = -− 0.03; − 0.02 to − 0.04; p = 0.01) in the normal range. At last measurement, 11.7% of the total population had a HbA1c < 7.0% (53.0 mmol/mol).

Conclusions

Across all measurements, coexisting T1D and CD is associated with lower HbA1c when compared to T1D alone. However, HbA1c is above target in both groups.
Efficacy and effectiveness of Herpes zoster vaccination in adults with diabetes mellitus: a systematic review and meta-analysis of clinical trials and observational studies
Authors: Silverii Giovanni Antonio , Clerico Alessandra , Fornengo Riccardo , Gabutti Giovanni , Sordi Valeria , Peruzzi Ottavia , Tafuri Silvio , Mannucci Edoardo , Dicembrini Ilaria
Published: June 2023

Aim

The risk for Herpes zoster (HZ) and its complications is higher in people with diabetes mellitus (DM). Our aim is to assess efficacy and effectiveness of the currently available live-attenuated zoster vaccine (LZV) and recombinant zoster vaccine (RZV) in adults with DM.

Methods

A Systematic Review and Meta-analysis of clinical trials and observational studies comparing incidence of HZ and its complications in vaccinated and unvaccinated people with DM was performed, on PubMed, Cochrane, Clinical Trials.gov and Embase databases, up to January 15th, 2023. Risk of bias was assessed through the Cochrane Collaboration tool and the Newcastle–Ottawa Scale. The protocol was registered on the PROSPERO website (CRD42022370705).

Results

Only three observational studies reported LZV efficacy and effectiveness in people with DM. A lower risk for HZ infection (MH-OH Ratio 95% CI = 0.52 [0.49, 0.56] was observed, for unadjusted analysis, and 0.51 [0.46, 0.56] for adjusted analysis, both with P < 0.00001 and no heterogeneity). No data on LZV safety were reported. A pooled analysis of two trials comparing RZV and placebo, showed a reduced risk for HZ incidence: (95% CI Odds Ratio: 0.09 [0.04–0.19]), with no difference in severe adverse events and mortality.

Conclusions

In our meta-analysis of three observational studies LZV showed a 48% effectiveness in reducing HZ incidence in adults with diabetes whereas in a pooled analysis of two RCTs, RZV showed a 91% efficacy. No data are available on the effects of vaccination on the incidence and severity of HZ-related complications among subjects with diabetes.
Potential role of human umbilical cord stem cells-derived exosomes as novel molecular inhibitors of hepatocellular carcinoma growth
Authors: ElBadre Hala M , El-Deek Sahar E M , Ramadan Haidi Karam-Allah , Elbadr Mohamed M , Sabry Dina , Ahmed Noran M , Ahmed Amr M , El-Mahdy Reham I
Published: June 2023

Hepatocellular carcinoma (HCC) is one of the most critical cancers; thus, novel therapeutical regimens are of great need. In this study, we investigated the effects of umbilical cord mesenchymal stem cells (UC-MSCs) derived exosomes on HepG2 cell line, and the underlying mechanism to control HCC proliferation, to identify the potential clinical role of exosomes as a novel molecular therapeutic target. Proliferation, apoptosis, and angiogenesis effects were assessed together with the cell viability evaluation by MTT assay in HepG2 cells at 24/48 h. with or without UC-MSCs-derived exosomes. Gene expressions of TNF-α, caspase-3, VEGF, stromal cell-derived factor-1 (SDF-1), and CX chemokine receptor-4 (CXCR-4) were measured by quantitative real-time PCR technique. Expression of sirtuin-1 (SIRT-1) protein was detected by western blot. Treatment of HepG2 cells with UC-MSCs-derived exosomes for 24 and 48 h. demonstrated a significant reduction of cells survival compared to the control group (p < 0.05). The SIRT-1 protein, and VEGF, SDF-1, CXCR-4 expression levels were significantly lower, TNF-α and caspase-3 expression levels were significantly higher in exosomal-treated HepG2 cells for 24 and 48 h. than those in the control group. Moreover, our findings documented that the anti-proliferative, apoptotic, and anti-angiogenic effects were achieved in a time-dependent manner in which more effects were determined after 48 h supplementation compared to 24 h (p < 0.05). UC-MSCs-derived exosomes exert anticarcinogenic molecular effects on HepG2 cells through the involvement of SIRT-1, SDF-1, and CXCR-4. Hence, exosomes would be a potential novel therapy regimen against HCC. Large-scale studies are recommended to verify this conclusion.
Establishing effective conservation management strategies for a poorly known endangered species: a case study using Australia’s Night Parrot (Pezoporus occidentalis)
Authors: Leseberg Nicholas P. , Kutt Alex , Evans Megan C. , Nou Tida , Spillias Scott , Stone Zoe , Walsh Jessica C. , Murphy Stephen A. , Bamford Mike , Burbidge Allan H. , Crossing Kate , Davis Robert A. , Garnett Stephen T. , Kavanagh Rodney P. , Murphy Robert , Read John , Reid Julian , van Leeuwen Stephen , Watson Alexander W. T. , Watson James E. M. , Maron Martine
Published: June 2023

An evidence-based approach to the conservation management of a species requires knowledge of that species’ status, distribution, ecology, and threats. Coupled with budgets for specific conservation strategies, this knowledge allows prioritisation of funding toward activities that maximise benefit for the species. However, many threatened species are poorly known, and determining which conservation strategies will achieve this is difficult. Such cases require approaches that allow decision-making under uncertainty. Here we used structured expert elicitation to estimate the likely benefit of potential management strategies for the Critically Endangered and, until recently, poorly known Night Parrot (Pezoporus occidentalis). Experts considered cat management the single most effective management strategy for the Night Parrot. However, a combination of protecting and actively managing existing intact Night Parrot habitat through management of grazing, controlling feral cats, and managing fire specifically to maintain Night Parrot habitat was thought to result in the greatest conservation gains. The most cost-effective strategies were thought to be fire management to maintain Night Parrot habitat, and intensive cat management using control methods that exploit local knowledge of cat movements and ecology. Protecting and restoring potentially suitable, but degraded, Night Parrot habitat was considered the least effective and least cost-effective strategy. These expert judgements provide an informed starting point for land managers implementing on-ground programs targeting the Night Parrot, and those developing policy aimed at the species’ longer-term conservation. As a set of hypotheses, they should be implemented, assessed, and improved within an adaptive management framework that also considers the likely co-benefits of these strategies for other species and ecosystems. The broader methodology is applicable to conservation planning for the management and conservation of other poorly known threatened species.
Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry
Authors: Martín Miguel , Carrasco Eva , Rodríguez-Lescure Álvaro , Andrés Raquel , Servitja Sonia , Antón Antonio , Ruiz-Borrego Manuel , Bermejo Begoña , Guerrero Ángel , Ramos Manuel , Santaballa Ana , Muñoz Montserrat , Cruz Josefina , Lopez-Tarruella Sara , Chacón Jose I. , Álvarez Isabel , Martínez Purificación , Miralles Juan J. , Polonio Óscar , Jara Carlos , Aguiar-Bujanda David
Published: June 2023

Purpose

The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib.

Methods

HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1–3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR).

Results

A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003–10 (210), and GEICAM-2006–10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%.

Conclusions

This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted.

Trial registration

ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.
Physicalism, Foundationalism, and Infinite Descent
Authors: Werner Jonas
Published: June 2023

This paper contributes to answering the question how physicalism can be defined for a world without fundamental physical phenomena. In a recent paper in this journal, Torin Alter, Sam Coleman, and Robert J. Howell propose a necessary condition on physicalism. They argue that physicalism is true only if there is no infinitely descending chain of mentally constituted phenomena. I argue that this alleged necessary condition faces counterexamples. An infinitely descending chain of mentally constituted phenomena is compatible with physicalism. Afterwards I propose a simpler definition of physicalism that does not fall prey to my counterexample.
The mental labyrinth of postgraduate research: a qualitative study of postgraduate mental health and wellbeing and the impact of the supervisory relationship
Authors: White Naomi , Milicev Jelena , Bradford Daniel R. R. , Rodger Amy , Gardani Maria
Published: June 2023

Postgraduate research students (PGRs) experience disproportionately high levels of psychological distress. Many factors contribute to this poor mental wellbeing and relate to each other in complex and dynamic ways. However, the relationship between PGRs and their supervisor(s) is known to strongly affect the wellbeing of the former. This study explores the mental health and wellbeing of PGRs with a focus on the role of the student—supervisor relationship. Using combined qualitative data from a large survey of PGRs and focus groups and reflexive thematic analysis, we found that PGRs experience the overarching process of obtaining a research degree as a mental labyrinth. Three constituent themes were identified: (1) inequity in navigating the labyrinth, (2) the labyrinth as a place of uncertainty and isolation, and (3) supervisors as labyrinth guides, not mental care providers. The results suggest that significant inequities exist which contribute to poorer mental wellbeing in particular subgroups of PGRs, both in general and specifically in relation to the supervisory relationship. Experiences of loneliness and ambiguity around progress were also identified as being detrimental to mental health. Furthermore, although supervisors can be a vital source of support and have a positive influence on PGR mental health, students recognise supervisors cannot reasonably be expected to act as professional mental health care providers and institutions must do more to provide equitable access to mental health support services.
Scientific collaboration amid geopolitical tensions: a comparison of Sweden and Australia
Authors: Shih Tommy , Chubb Andrew , Cooney-O’Donoghue Diarmuid
Published: June 2023

Significant collaborations with research partners in China are seen in many Western countries. With increasing US-China geopolitical tensions, governments, research institutions, and individuals in established scientific systems are increasingly required to address a proliferating array of risks and challenges associated with collaboration with China. Academic researchers are only beginning to describe how countries are responding to the ongoing need for global scientific collaboration amidst intensifying geopolitical competition. Several studies have examined the securitization of scientific connections with China in the USA, while others have documented developments in nations such as Australia, the UK, and Sweden. However, there is limited comparative research on approaches to international science amid geopolitical tensions. This paper bridges the gap, illuminating the key dimensions of variation in country-level responses by comparing the cases of Sweden and Australia. The questions we ask are as follows: Who responds to the challenges? By what means? And to what ends are responses directed? Swedish government have been largely passive, but Swedish funding agencies have developed “responsible internationalisation” guidelines that aim to induce proactive reflection by institutions and individual researchers. Australia’s approach, by contrast, has centred on legislation, the exercise of ministerial powers, along with sector-wide enactment of expanded due diligence protocols. The comparison highlights key differences in the actors, methods and goals of responses to the intensifying geopolitics of scientific collaboration.
Current and historical patterns of recruitment of Yellowstone cutthroat trout in Yellowstone Lake, Wyoming, as revealed by otolith microchemistry
Authors: Stewart Kole P. , McMahon Thomas E. , Koel Todd M. , Humston Robert
Published: June 2023

Yellowstone cutthroat trout inhabiting Yellowstone Lake have declined substantially over the past 25 years as a result of predation by invasive lake trout, the presence of whirling disease, and periods of persistent drought. We used otolith microchemistry to assess whether cutthroat trout recruitment patterns have changed in response to these environmental stressors. Though water chemistry variation among the 22 sampled spawning tributaries was low, we identified 9 distinct spawning stream clusters. Random forest models were developed for assessing relative recruitment, yielding a high classification accuracy of 84.4% for known-origin cutthroat trout fry otoliths and 79.0% for simulated otolith signatures based on water chemistry. Proportion of recruitment varied significantly between pre- and post-stressor samples (X2 = 15.40,P = 0.03). The majority of pre- (0.84) and post-stressor (0.77) recruitment occurred in the same three stream clusters, but there was a notable decrease in recruitment in streams with high whirling disease prevalence, and a notable increase from the tributary cluster without whirling disease and with low lake trout predation risk. Conservation efforts should be focused on protecting important spawning tributaries and improving cutthroat trout recruitment in spawning streams that in the past likely contributed much greater numbers of fish.
Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study
Authors: Tambe Prasad Kisan , Qsee H. S. , Bharati Sanjay
Published: June 2023

Background

Recent evidences highlight role of mitochondria in the development of 5-fluorouracil (5-FU)-induced intestinal toxicity. Mitochondria-targeted antioxidants are well-known for their protective effects in mitochondrial oxidative stress- mediated diseases. In the present study, we investigated protective effect of Mito-TEMPO in 5-FU-induced intestinal toxicity.

Methods

Mito-TEMPO (0.1 mg/kg b.w.) was administered intraperitoneally to male BALB/c mice for 7 days, followed by co-administration of 5-FU for next 4 days (intraperitoneal 12 mg/kg b.w.). Protective effect of Mito-TEMPO on intestinal toxicity was assessed in terms of histopathological alterations, modulation in inflammatory markers, apoptotic cell death, expression of 8-OhDG, mitochondrial functional status and oxidative stress.

Results

5-FU administered animals showed altered intestinal histoarchitecture wherein a shortening and atrophy of the villi was observed. The crypts were disorganized and inflammatory cell infiltration was noted. Mito-TEMPO pre-protected animals demonstrated improved histoarchitecture with normalization of villus height, better organized crypts and reduced inflammatory cell infiltration. The inflammatory markers and myeloperoxidase activity were normalized in mito-TEMPO protected group. A significant reduction in intestinal apoptotic cell death and expression of 8-OhDG was also observed in mito-TEMPO group as compared to 5-FU group. Further, mtROS, mtLPO and mitochondrial antioxidant defense status were improved by mito-TEMPO.

Conclusion

Mito-TEMPO exerted significant protective effect against 5-FU-induced intestinal toxicity. Therefore, it may be used as an adjuvant in 5-FU chemotherapy.
From Blind Spot to Crucial Concept: On the Role of Animal Welfare in Food System Changes towards Circular Agriculture
Authors: Meijboom Franck L.B. , Staman Jan , Pothoven Ru
Published: June 2023

Agriculture in Western Europe has become efficient and productive but at a cost. The quality of biodiversity, soil, air, and water has been compromised. In the search for ways to ensure food security and meet the challenges of climate change, new production systems have been proposed. One of these is the transition to circular agriculture: closing the cycles of nutrients and other resources to minimise losses and end the impact on climate change. This development aims to address existing problems in food production but also raises questions about animal health and welfare. Although the role animals can play in this development is not ignored, the animal welfare dimension of circular agriculture seems to be overlooked. We argue that this is a problem both for the success of circular agriculture and for the animals involved. To substantiate this claim, we analyse the background to this lack of attention, which we find in (a) the way circular agriculture is conceptualised; (b) the institutional hurdles related to the legal, political and economic context; and (c) the concept of animal welfare, which requires further innovation. By analysing these aspects, we develop stepping stones for an animal-welfare inclusive concept of circular agriculture. These stepping stones include: recognising the animal as a participant with its own interests in the innovation towards circular agriculture; using a dynamic concept of animal welfare; a concept of circularity that provides space for social values, including animal welfare; and attention to institutional innovation by improving public engagement and building trust.
Propagation of Chaos for Weakly Interacting Mild Solutions to Stochastic Partial Differential Equations
Authors: Criens David
Published: June 2023

This article investigates the propagation of chaos property for weakly interacting mild solutions to semilinear stochastic partial differential equations whose coefficients might not satisfy Lipschitz conditions. Furthermore, we establish existence and uniqueness results for mild solutions to SPDEs with distribution dependent coefficients, so-called McKean–Vlasov SPDEs.
A Versatile Stochastic Dissemination Model
Authors: Chan K. M. D. , Mandjes M. R. H.
Published: June 2023

This paper considers a highly general dissemination model that keeps track of the stochastic evolution of the distribution of wealth over a set of agents. There are two types of events: (i) units of wealth externally arrive, and (ii) units of wealth are redistributed among the agents, while throughout Markov modulation is allowed. We derive a system of coupled differential equations describing the joint transient distribution of the agents’ wealth values, which translate into linear differential equations when considering the corresponding means and (co-)variances. While our model uses the (economic) terminology of wealth being distributed over agents, we illustrate through a series of examples that it can be used considerably more broadly. Indeed, it also facilitates the analysis of the spread of opinions over a population (thus generalizing existing opinion dynamics models), and the analysis of the dynamics of a file storage system (thus allowing the assessment of the efficacy of storage policies).
Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats
Authors: Zhan Haohong , Zhang Qiang , Zhang Chenyu , Cheng Jingge , Yang Yilin , Liu Cong , Li Shuhao , Wang Chuyue , Yang Junqin , Ge Hanmei , Zhou Dawang , Li Bo , Wei Hongyan , Hu Chunlin
Published: June 2023

Previous studies have shown that AMPK plays an important role in cerebral ischemia–reperfusion injury by participating in apoptosis, but the exact mechanism and target of action remains unclear. This study aimed to investigate the protective mechanism of AMPK activation on brain injury secondary to cardiac arrest. HE, Nills and TUNEL assays were used to evaluate neuronal damage and apoptosis. The relationships between AMPK, HNF4α and apoptotic genes were verified by ChIP-seq, dual-luciferase and WB assays. The results showed that AMPK improved the 7-day memory function of rats, and reduced neuronal cell injury and apoptosis in the hippocampal CA1 region after ROSC, while the use of HNF4α inhibitor weakened the protective effect of AMPK. Further research found that AMPK positively regulated the expression of HNF4α, and AMPK could promote the expression of Bcl-2 and inhibit the expression of Bax and Cleaved-Caspase 3. In vitro experiments showed that AMPK ameliorated neuronal injury by inhibiting apoptosis through the activation of HNF4α. Combined with ChIP-seq, JASPAR analysis and Dual-luciferase assay, the binding site of HNF4α to the upstream promoter of Bcl-2 was found. Taken together, AMPK attenuates brain injury after CA by activating HNF4α to target Bcl-2 to inhibit apoptosis.
Preliminary insights from hydrological field monitoring for the evaluation of landslide triggering conditions over large areas
Authors: Schilirò Luca , Marmoni Gian Marco , Fiorucci Matteo , Pecci Massimo , Mugnozza Gabriele Scarascia
Published: June 2023

Rainfall-induced landslides represent a major threat to human activities, and thus an improved understanding of their triggering mechanisms is needed. The paper reports some preliminary inferences on this topic, based on the data recorded over a 2-year period by a multi-parametric monitoring station located on one of the slopes of the Monterosso catchment (Cinque Terre, north-western Italy). This catchment has experienced multiple, concurrent shallow landslides after intense rainfall events. After defining a soil hydraulic model through data interpretation and numerical simulations, slope stability analyses were performed to elucidate several aspects related to shallow landslide occurrence. Both long-term climate conditions and single rainfall events were simulated via physically based approaches. The findings from these simulations enabled us to assume the pattern of infiltration and quantify the impact of soil hydraulic behavior on landslide triggering conditions. In this regard, various analyses were carried out on the same triggering event both at local scale and in the overall catchment, with a view to highlighting the role of initial soil moisture and soil hysteretic behavior in slope stability.
Sociodemographic factors and use of pain medication are associated with health-related quality of life: results from an adult community mental health service in Norway
Authors: Lindberg Martin Schevik , Brattmyr Martin , Lundqvist Jakob , Roos Eirik , Solem Stian , Hjemdal Odin , Havnen Audun
Published: June 2023

Purpose

Health-related quality of life (HRQoL) is an important aspect of mental health outcomes. There are few studies on HRQoL in heterogeneous patient populations seeking help at community mental health services. The aims of the study were to compare how HRQoL, measured by the EuroQol five dimensions with five levels (EQ-5D-5L), was distributed compared to other samples from national and international studies, and to explore what factors are associated with HRQoL.

Methods

In a cross-sectional study, 1379 Norwegian outpatients reported their HRQoL before starting treatment. Associations with demographic variables, job status, socio-economic status, and use of pain medication were examined using multiple regression analysis.

Results

Most of the sample, 70% to 90%, reported problems with usual activities, pain/discomfort, and anxiety/depression; 30% to 65% reported that these problems were of a moderate to extreme degree. Forty percent reported problems with mobility, and about 20% reported problems with self-care. The sample’s HRQoL was considerably lower than the general population, and comparable to patient-groups from specialist mental health services. Originating from a developing country, lower level of education, lower yearly household income, being on sick leave or unemployed, and using pain medication were associated with lower HRQoL. Age, gender, and relationship status were not associated with HRQoL. This is the first study to simultaneously examine the unique contribution of these variables in one study.

Conclusion

The most impacted domains of HRQoL were pain/discomfort, anxiety/depression, and usual activities. Lower HRQoL was associated with several socio-demographic factors and use of pain medication. These findings might have clinical implications and suggest that mental health professionals should routinely measure HRQoL in addition to symptom severity, to identify areas that should be targeted to improve HRQoL.
No Evidence for Absence of Solar Dynamo Synchronization
Authors: Stefani F. , Beer J. , Weier T.
Published: June 2023

The old question of whether the solar dynamo is synchronized by the tidal forces of the orbiting planets has recently received renewed interest, both from the viewpoint of historical data analysis and in terms of theoretical and numerical modeling. We aim to contribute to the solution of this longstanding puzzle by analyzing cosmogenic radionuclide data from the last millennium. We reconsider a recent time series of 14C-inferred sunspot data and compare the resulting cycle minima and maxima with the corresponding conventional series down to 1610 A.D., enhanced by Schove’s data before that time. We find that, despite recent claims to the contrary, the 14C-inferred sunspot data are well compatible with a synchronized solar dynamo, exhibiting a relatively phase-stable period of 11.07 years, which points to a synchronizing role of the spring tides of the Venus-Earth-Jupiter system.