bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term captivity is associated with changes to sensory organ morphology in a critically endangered insect
Authors: Freelance Christopher B. , Magrath Michael J. L. , Elgar Mark A. , Wong Bob B. M. 
Published: October 2021

Abstract

Captive breeding programmes are key to many threatened species reintroduction strategies but could potentially be associated with adaptations to captivity that are maladaptive in their natural habitat. Despite the importance of sensory ecology to biological fitness, few studies explore sensory system adaptations to captivity. Captive environments are devoid of predators and provide ready access to food sources and potential mates, thus reducing the need for individuals to use signals and cues to identify and locate resources or detect potential threats. With reduced complexity of the signalling environment, relaxation of selective pressures may favour reduced investment in sensory organs in captivity.

We test this prediction in an iconic critically endangered invertebrate, the Lord Howe Island stick insect Dryococelus australis, which was extirpated from the island in the 1920s/30s and rediscovered on a nearby volcanic stack, Ball's Pyramid, in 2001.

Using historical specimens from these populations and specimens from the 8–10th and 14th generations of a long‐term conservation captive breeding programme, we examine differences in behaviourally relevant morphological traits of the compound eyes (visual organs) and antennae (olfactory organs).

We find that captivity is associated with smaller compound eye size, smaller eye ommatidia and reduced density of antennal odour receptors. These morphological changes are indicative of reduced sensitivity to visual and olfactory signals and cues, and therefore are likely to have fitness implications when reintroducing a captive population into the wild.

Synthesis and applications. We observe differences in sensory organ morphology between wild and captive‐bred populations of the critically endangered Lord Howe Island stick insect. Our results emphasise the importance of incorporating evolutionary biology and sensory ecology into conservation programme design: to minimise the potential for captive breeding environments to compromise sensory systems that support appropriate behaviours upon reintroduction of populations into a natural habitat.
Optimizing flower fields as an effective farmland eco‐scheme also during non‐breeding
Authors: Rieger Mirjam R. , Mailänder Sarah , Stier Lea , Santon Matteo , Staggenborg Julia , Anthes Nils 
Published: October 2021

Abstract

The Common Agricultural Policy (CAP) of the European Union implements several farmland eco‐schemes, but most are considered ineffective in halting the population declines of farmland birds. Sown flower fields are among the few eco‐scheme types that rate as clearly beneficial. Yet, current CAP regulations lack minimum criteria for flower fields to qualify as eco‐scheme, and thus only partially exploit their potential biodiversity benefits.

Earlier research on the attraction of farmland birds to different types of sown flower fields has focused on the breeding season. We know far less about relative use of these fields during the non‐breeding season, when food limitation can become severe. We therefore compared the attractiveness of four flower field types in SW Germany to 17 bird species during autumn and winter. Based on replicate surveys on 75–168 fields, we analysed bird incidences across these four types, and in relation to vegetation structure and landscape features.

Flower field types showed little variation in species richness, but striking differences in selection by particular species. Finches and tits were disproportionally abundant on fields in their first year since sowing, buntings and whinchat on fields in later successional stages. Most flower fields established under CAP greening regulations were ploughed between September and November in their sowing year. Therefore, such fields fail to support farmland birds and other wildlife during a critical phase in their annual cycle.

Birds were consistently more abundant on larger fields with a differentiated vegetation structure. Flower fields along hedgerows and groves primarily attracted inhabitants of woodland ecotones, while farmland birds had higher incidences on fields embedded in open landscapes.

Policy implications. EU member states currently revise their regulations for farmland eco‐schemes, including sown flower fields. We propose minimum quality standards to assure that such fields effectively support farmland birds also during the non‐breeding season. Standards include a minimum maintenance for two years, more diversified seed mixtures, field sizes exceeding 12 m width or 0.18 ha area, and local diversity in flower field placement relative to other landscape elements such as hedgerows.
Response and safety of whole‐brain radiotherapy plus temozolomide for patients with brain metastases of non‐small‐cell lung cancer: A meta‐analysis
Authors: Han Jianguo , Qiu Ming , Su Li , Wu Chong , Cheng Si , Zhao Zhijun , Li Danxia , Wang Menghui , Tao Wei , Du Shiwei 
Published: October 2021

AbstractObjectiveThe aim of the present work was to investigate the response and safety of whole‐brain radiotherapy (WBRT) plus temozolomide (TMZ) for patients with brain metastases of non‐small‐cell lung cancer (NSCLC).MethodsThe electronic databases of Pubmed, EMbase, Cochrane, Wangfang, china national knowledge infrastructure (CNKI), and Google scholar were systematically searched to identify the prospective randomized trials relevant to WBRT plus TMZ for patients with brain metastases of NSCLC. The data associated with treatment response and toxicity were extracted from original included studies. The relative risk (RR) for treatment response and toxicity between WBRT+TMZ and WBRT alone was pooled by fixed or random effect model. Publication bias was investigated by Begg's funnel plot and Egger's line regression test.ResultsTwenty‐five clinical trials fulfilled the inclusion criteria and were included in the meta‐analysis. The pooled results showed WBRT+TMZ can significant improve the objective response rate (ORR) compared with WBRT alone (RR = 1.43, 95% confidence interval [CI] 1.32–1.55, p < 0.05) under a fixed effect model. WBRT+TMZ significantly increased the III–IV hematological toxicity compared to WBRT alone (RR = 1.66, 95% CI 1.12–2.54, p < 0.05) in the fixed effect model. Grade III–IV gastrointestinal toxicity was increased in WBRT+TMZ compared to WBRT alone (RR = 1.72, 95% CI 1.29–2.30, p < 0.05). Begg's funnel plot and Egger's line regression test indicated publication bias.ConclusionBased on the present work, WBRT+TMZ can improve the ORR for brain metastases of NSCLC, but the risk of treatment‐associated grade III/IV hematological toxicity and gastrointestinal toxicity were also increased compared to WBRT alone.
Spatio‐temporal variation in tick community composition and abundance in a wildlife–livestock interface within Nyanga National Park, Zimbabwe
Authors: Mutizhe Silas W. , Mhlanga Lindah , Sithole Rudo , Maya Banele T. , Sibanda Artwell , Mpofu Protect 
Published: October 2021

AbstractHuman settlement expansion around Nyanga National Park has led to increased wildlife–livestock interaction. Tick community dynamics was evaluated in high, medium and low wildlife–livestock interaction sectors designated by extent of livestock incursions. Out of a total of 4281 ticks recorded, 39.8% were Rhipicephalus zambeziensis and 28.2% Rhipicephalus appendiculatus. Hyalomma truncatum, Rhipicephalus simus, Rhipicephalus decoloratus and Amblyomma variegatum were each less than seven percent, whereas Hyalomma rufipes, Rhipicephalus compositus, Amblyomma hebraeum, Rhipicephalus evertsi evertsi and Haemaphysalis leachi were each less than three percent. Tick species richness (S = 11) was highest in high interaction sectors. Amblyomma variegatum, A. hebraeum, R. compositus and R. eversti evertsi did not occur in low interaction sectors, whereas Ha. leachi was not recorded within shrublands and at high altitude. Tick abundance (p = 0.046) and diversity (p = 0.044) were only significantly influenced by interaction intensity. This could be attributed to greater host availability and increased animal bidirectional movement across the interface. Tick abundance was highest during summer. Tick dense spatial distribution was projected in areas where interaction is high. Increased interaction will increase abundance and spread of ticks into new areas within the park unless strategies to prevent animal bidirectional movement are instituted.
A retrospective cohort study of tubal occlusion or salpingectomy for permanent contraception in Australia
Authors: Baltus Tanja , Brown James , Kapurubandara Supuni 
Published: October 2021

Background:Laparoscopic permanent contraception was previously accomplished most commonly using tubal occlusion procedures. Bilateral salpingectomy (BS) has recently been introduced as an alternative due to possibly superior contraception and greater protection against ovarian cancer.Aims:The aim of this study is to assess uptake, feasibility and perioperative outcomes of laparoscopic BS as an alternative to tubal occlusion in Australia.Materials and Methods:A retrospective review of permanent female contraception at two Australian hospitals from January 2014 through December 2020 was performed. The primary outcome was the uptake of BS. Secondary outcomes were feasibility, procedure length, number of ports, perioperative complications and admission length.Results:A total of 414 women were included; 92 (22.2%) underwent BS and 322 (77.8%) underwent tubal occlusion. There was a slow uptake of BS from 2014 to 2016 (0–3.2%), with a steep uptake from 2017 to 2020 (30–72%) (P = 0.001). Procedure feasibility was 96.8% (62/64) and 99.3% (282/284) for BS and tubal occlusion group, respectively (P = 0.64). BS procedure time was longer by 23 min (P < 0.001). Three or more surgical ports were used in all cases of BS compared to 4.5% of the tubal occlusion group (P < 0.001). There were no intraoperative complications. There were nine and six postoperative complications in the tubal occlusion versus BS group, respectively (P = 0.10). The median admission length was 7.1 (tubal occlusion) versus 7.3 (BS) h (P = 0.10), with five unintended overnight admissions.Conclusion:BS is an increasing choice for permanent contraception. It appears equally feasible as tubal occlusion but typically requires a longer procedure time and a minimum of three surgical ports.
Characteristics of COVID‐19 patients up to 6 months of age admitted to a paediatric emergency department
Authors: Bellini Tommaso , Rotulo Gioacchino Andrea , Caruggi Samuele , Carta Sabina , Bonato Irene , Piccotti Emanuela 
Published: October 2021

AbstractVery young age could be a potential risk factor for community‐acquired severe acute respiratory syndrome coronavirus 2, due to immature immune systems. We retrospectively enrolled 39 infants up to 6 months of age who had presented to our tertiary Italian children's hospital emergency room between 9 March 2020 and 8 March 2021 and tested positive for the virus. Of those, 38 had a non‐specific mild or asymptomatic clinical course and only one patient was admitted to intensive care with severe symptoms. We concluded that very young infants with COVID‐19 had a generally favourable disease course.
Impact of target‐mediated drug disposition on hetrombopag pharmacokinetics and pharmacodynamics in Chinese healthy subjects and patients with chronic idiopathic thrombocytopenic purpura
Authors: Wang Zhenlei , Zeng Zhijun , Ye Lijun , Zhu Xiaohong , Pei Yuwen , Wang Yongsheng , Zheng Li 
Published: October 2021

AimsThe pharmacokinetics (PK) of hetrombopag were found to be nonlinear across evaluated dose ranges. The aim of this study was to develop a mechanism‐based population pharmacokinetic/pharmacodynamic (PopPK/PD) model and to provide a reasonable expected therapeutic dose for a future confirmatory clinical study of hetrombopag.MethodsNonlinear mixed‐effects modelling was performed using pooled 2168 hetrombopag concentrations and 1526 platelet counts from 72 healthy subjects and 32 chronic idiopathic thrombocytopenic purpura (ITP) patients from two phase I studies and one phase II study. The final model was evaluated via goodness‐of‐fit plots, visual predictive check and nonparametric bootstrap. Simulations from the validated PopPK/PD model were used to devise an expected therapeutic dose for later confirmatory clinical study.ResultsThe pharmacokinetic data of hetrombopag were well described by a modified target‐mediated drug disposition (TMDD) model with dual sequential first‐order absorption. Mean parameter estimates (interindividual variability) were CL/F 7.66 L/h (63.5%), Vc/F 30.0 L (77.2%) and Kdeg 0.693/h (87.1%). The pharmacodynamic profile was well described by a five‐compartment lifespan model with four‐transit and one‐platelet compartments. Simulation results suggested that chronic ITP patients following 10 mg once‐daily hetrombopag would able to achieve an ideal platelet count level (50‐200 × 109/L).ConclusionTMDD was the primary reason leading to nonlinear PK profile of hetrombopag. Our PK/PD modelling and simulation results support 10 mg once‐daily as the recommended therapeutic dose for chronic ITP patients in subsequent confirmatory clinical study of hetrombopag.
Cytoreductive nephrectomy and exposure to sunitinib – a post hoc analysis of the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial
Authors: Abu‐Ghanem Yasmin , van Thienen Johannes V. , Blank Christian , Aarts Maureen J. B. , Jewett Michael , de Jong Igle Jan , Lattouf Jean‐Baptiste , van Melick Harm H. E. , Wood Lori , Mulders Peter , Rottey Sylvie , Wagstaff John , Zondervan Patricia , Powles Tom , Neven Anouk , Collette Laurence , Tombal Bertrand , Haanen John , Bex Axel 
Published: October 2021

AbstractObjectiveTo analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm.Patients and MethodsA post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention‐to‐treat population of the immediate and deferred arm. Descriptive methods and 95% confidence‐intervals (CI) were used.ResultsIn the deferred arm, 97.7% (95% CI 89.3–99.6%; n = 48) received sunitinib vs 80% (95% CI 66.9–88.7%, n = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm.ConclusionsIn comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit.
Model‐informed assessment of ethnic sensitivity and dosage justification for Asian populations in the global clinical development and use of cladribine tablets
Authors: Munafo Alain , Terranova Nadia , Li Dandan , Liu Ping , Venkatakrishnan Karthik 
Published: October 2021

AbstractCladribine tablets have been approved in many countries for the treatment of patients with various forms of relapsing multiple sclerosis (MS). Cladribine has a unique pharmacokinetic/pharmacodynamic (PK/PD) profile with a short elimination half‐life (~ 1 day) relative to a prolonged PD effect on specific immune cells (most notably a reversible reduction in B and T lymphocyte counts). This results in a short dosing schedule (up to 20 days over 2 years of treatment) to sustain efficacy for at least another 2 years. Global clinical studies were conducted primarily in White patients, in part due to the distinctly higher prevalence of MS in White patients. Given the very low prevalence in Asian countries, MS is considered as a rare disease there. In spite of the limited participation of Asian patients, to demonstrate favorable benefit/risk profile in the treatment of MS demanded application of a Totality of Evidence approach to assess ethnic sensitivity for informing regulatory filings in Asian countries and supporting clinical use of cladribine in Asian patients. Population PD modeling and simulation of treatment‐related reduction in absolute lymphocyte count, as a mechanism‐related biomarker of drug effect, confirmed consistent PDs in Asian and non‐Asian patients with MS, supporting absence of ethnic sensitivity and a common dosage across populations. Through this example, we demonstrate the value of holistic integration of all available data using a model‐informed drug development (MIDD) framework and a Totality of Evidence mindset to evaluate ethnic sensitivity in support of Asia‐inclusive development and use of the drug across populations.
Primary cutaneous anaplastic large‐cell lymphoma with aberrant cytokeratin expression: An unusual mimicker of poorly differentiated carcinomas
Authors: Lee Jack , Jiang Hong , Gru Alejandro A. 
Published: October 2021

AbstractAn 81‐year‐old male presented with a rapidly growing cheek nodule. Biopsy revealed a dermal infiltrate of large atypical cells, some exhibiting a horseshoe‐shaped nucleus. Immunohistochemistry revealed positivity for CD4, CD3, CD45, and CD30 (>95%). Melanocytic markers, cytotoxic markers, CD20, CD56, ALK1, synaptophysin, CD1a, and ETS‐related gene (ERG) were negative. Notably, there was weak but diffuse expression of pan‐cytokeratin (AE1/AE3) and Oscar keratin. There was also a weak expression of epithelial membrane antigen (EMA). CAM 5.2, p40, and IRF4/DUSP22 rearrangement were negative. Further staging revealed skin‐limited disease. A diagnosis of primary cutaneous anaplastic large‐cell lymphoma (PC‐ALCL) was rendered. We present a rare case of cytokeratin positive PC‐ALCL, a finding never reported in the literature. Both PC‐ALCL and systemic ALCL (S‐ALCL) evoke a broad differential. CD45, EMA, and cytokeratin stains help differentiate from metastatic carcinomas. There have been rare prior reports of cytokeratin expression in S‐ALCL, which tend to stain with an unusual cytoplasmic and membranous pattern like our case, have variable co‐expression of EMA, and null T‐cell phenotypes. These show the significant diagnostic challenges that can arise in differentiating ALCL from metastatic or primary skin carcinomas. Awareness, careful attention to morphology (e.g., hallmark cells), and considering routine CD30 can help lead the pathologist to the correct diagnosis.
Health service use among adults with cerebral palsy: a mixed‐methods systematic review
Authors: Manikandan Manjula , Kerr Claire , Lavelle Grace , Walsh Michael , Walsh Aisling , Ryan Jennifer M 
Published: October 2021

AimTo determine the proportion of adults with cerebral palsy (CP) using health services and frequency of use, and to explore experiences and perceptions of health services for this population.MethodA mixed‐methods systematic review was conducted using the Joanna Briggs Institute methodology. Five databases were searched to September 2020. Observational and qualitative studies were included. Two reviewers screened titles, abstracts, and full texts; extracted data; and assessed the quality of included studies. Separate meta‐analyses were used to pool the proportion of adults using each service and frequency of use. A meta‐aggregation approach was used to synthesize qualitative data. Quantitative and qualitative findings were integrated using the Andersen and Newman Model of health care utilization.ResultsFifty‐seven studies (31 quantitative, 26 qualitative) of 14 300 adults with CP were included. The proportion of adults using services ranged from 7% (95% confidence interval [CI]: 2–13%) for urologists to 84% (95% CI: 78–90%) for general practitioners. Incidence of visits ranged from 67 (95% CI: 37–123) hospital admissions to 404 (95% CI: 175–934) general practitioner visits per 100 person‐years. Qualitative themes highlighted issues regarding accessibility, caregivers’ involvement, health workers’ expertise, unmet ageing needs, transition, and health system challenges.InterpretationAdults with CP used a wide range of health services but faced context‐specific challenges in accessing required care. Appropriate service delivery models for adults with CP are required. This review emphasizes a need to develop an appropriate service model for adults with CP to meet their needs.
Delayed perihematomal hypoperfusion is associated with poor outcome in intracerebral haemorrhage
Authors: Morotti Andrea , Busto Giorgio , Boulouis Gregoire , Scola Elisa , Bernardoni Andrea , Fiorenza Alessandro , Amadori Tommaso , Carbone Federico , Casetta Ilaria , Montecucco Fabrizio , Fainardi Enrico 
Published: October 2021

AbstractBackgroundThe aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH).MethodsA single‐centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6 h from onset (T0) and at 7 days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low‐density area. Poor functional prognosis (modified Rankin Scale 3–6) at 90 days was the outcome of interest, and predictors were explored with multivariable logistic regression.ResultsA total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3–6 at 90 days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change −7.8 vs. −6.0 ml/100 g/min, p < .001, and median CBV change −0.5 vs. −0.4 ml/100 g, p = .010, respectively). This finding remained significant after adjustment for confounders (odds ratio [OR] for 1 ml/100 g/min CBF reduction: 1.33, 95% confidence interval [CI] (1.15–1.55), p < .001; OR for 0.1 ml/100 g CBV reduction: 1.67, 95% CI 1.18–2.35, p = .004). The presence of CBF < 20 ml/100 g/min at T7 was then demonstrated as an independent predictor of poor functional outcome (adjusted OR: 2.45, 95% CI 1.08–5–54, p = .032).ConclusionPerihaemorrhagic hypoperfusion becomes more severe in the days following acute ICH and is independently associated with poorer outcome. Understanding the underlying biological mechanisms responsible for delayed decrease in perihematomal perfusion is a necessary step towards outcome improvement in patients with ICH.