bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraints on the paleoelevation history of the Eastern Cordillera of Colombia from its palynological record
Authors: Molnar Peter , Pérez-Angel Lina C. 
Published: June 2021

Abstract
We attempted to make an objective assessment of whether fossil pollen assemblages from the Sabana de Bogotá require surface uplift of ~2000 m since 6–3 Ma, as has been argued. We relied on recently published elevation ranges of plants for which fossil pollen has been found in sites 2000–2500 m high in the Sabana de Bogotá. The elevation ranges of fossil plants do not overlap, suggesting that those ranges may be too narrow. By weighting these elevation ranges by percentages of corresponding fossil pollen and summing them, we estimated probability density functions for past elevations. These probability distributions of past elevations overlap present-day elevations and therefore do not require surface uplift since deposition of the pollen. Fossil pollen assemblages include pollen from some plant taxa for which we do not know present-day elevation ranges, and therefore, with a more complete knowledge of elevation distributions, tighter constraints on elevations should be obtainable. The elevation of the oldest assemblage, from Tequendama, which lies at the southern edge of the Sabana de Bogotá and is thought to date from 16 to 6 Ma, is least well constrained. Although our analysis permits no change in elevation since the pollen was deposited, we consider 1000–2000 m of elevation gain since 15 Ma to be likely and consistent with an outward growth of the Eastern Cordillera.
Return to sport decisions after an acute lateral ankle sprain injury: introducing the PAASS framework—an international multidisciplinary consensus
Authors: Smith Michelle D , Vicenzino Bill , Bahr Roald , Bandholm Thomas , Cooke Rosalyn , Mendonça Luciana De Michelis , Fourchet François , Glasgow Philip , Gribble Phillip A , Herrington Lee , Hiller Claire E , Lee Sae Yong , Macaluso Andrea , Meeusen Romain , Owoeye Oluwatoyosi B A , Reid Duncan , Tassignon Bruno , Terada Masafumi , Thorborg Kristian , Verhagen Evert , Verschueren Jo , Wang Dan , Whiteley Rod , Wikstrom Erik A , Delahunt Eamonn 
Published: June 2021

BackgroundDespite being the most commonly incurred sports injury with a high recurrence rate, there are no guidelines to inform return to sport (RTS) decisions following acute lateral ankle sprain injuries. We aimed to develop a list of assessment items to address this gap.MethodsWe used a three-round Delphi survey approach to develop consensus of opinion among 155 globally diverse health professionals working in elite field or court sports. This involved surveys that were structured in question format with both closed-response and open-response options. We asked panellists to indicate their agreement about whether or not assessment items should support the RTS decision after an acute lateral ankle sprain injury. The second and third round surveys included quantitative and qualitative feedback from the previous round. We defined a priori consensus being reached at >70% agree or disagree responses.ResultsSixteen assessment items reached consensus to be included in the RTS decision after an acute lateral ankle sprain injury. They were mapped to five domains with 98% panellist agreement—PAASS:Pain (during sport participation and over the last 24 hours),Ankle impairments (range of motion; muscle strength, endurance and power),Athlete perception (perceived ankle confidence/reassurance and stability; psychological readiness),Sensorimotor control (proprioception; dynamic postural control/balance),Sport/functional performance (hopping, jumping and agility; sport-specific drills; ability to complete a full training session).ConclusionExpert opinion indicated that pain severity, ankle impairments, sensorimotor control, athlete perception/readiness and sport/functional performance should be assessed to inform the RTS decision following an acute lateral ankle sprain injury.Trial registration numberACTRN12619000522112.
Man with headache and altered mental status
Authors: Prucnal Christiana K , Jansson Paul S 
Published: June 2021

PresentationAn 83-year-old man presented for headache and altered mental status. Four days prior, he underwent endoscopic sinus surgery for nasal polyps. Over the two previous days, he gradually developed a headache and was brought to the emergency department when his wife noted mild confusion and generalised weakness. His examination was notable for a heart rate of 101 beats per minute, clear nasal discharge, meningismus and confusion to the date with generalised weakness. A lumbar puncture revealed cloudy cerebrospinal fluid (CSF) with a white blood cell count of 3519x10ˆ9/L (95% neutrophils). A CT scan of the head was obtained (figure 1).Figure 1Non-contrast CT scan of the head in axial plane.QuestionWhat is the appropriate next step in management?Obtain MRI of the brain to localise ischaemic damage.Administer broad-spectrum antibiotics, includingpseudomonalcoverage.Consult otolaryngology to arrange functional endoscopic sinus surgery for CSF leak closure.Consult neurosurgery for surgical decompression of mass lesion(s).
Impact of cuts to local government spending on Sure Start children’s centres on childhood obesity in England: a longitudinal ecological study
Authors: Mason Kate E , Alexiou Alexandros , Bennett Davara Lee , Summerbell Carolyn , Barr Ben , Taylor-Robinson David 
Published: June 2021

BackgroundChildhood obesity is rising in disadvantaged areas in England. Sure Start children’s centres provide community-based services for children <5 years and their parents, including many services that can support healthy weight, directly or indirectly. Since 2010, austerity-driven cuts to local authority (LA) budgets have led to substantially reduced public expenditure on Sure Start services. We assessed whether childhood obesity prevalence has increased more since 2010 in those areas in England that experienced greater cuts to spending on Sure Start.MethodsThis longitudinal ecological study covers the period 2010/2011–2017/2018. Our exposure was LA expenditure on Sure Start, using Department for Education data. Our main outcome was LA obesity prevalence at age 4–5 years, using National Child Measurement Programme data. We used fixed-effects panel regression to quantify the association between change in spending and change in the prevalence of childhood obesity.ResultsSpending on Sure Start children’s centres decreased on average 53% over the study period, with deeper cuts in more deprived LAs. Each 10% spending cut was associated with a 0.34% relative increase in obesity prevalence the following year (95% CI 0.15% to 0.53%). We estimated there were an additional 4575 children with obesity (95% CI 1751 to 7399) and 9174 overweight or obese (95% CI 2689 to 15 660) compared with expected numbers had funding levels been maintained.ConclusionsCuts to spending on Sure Start children’s centres were associated with increased childhood obesity. With deprived areas experiencing bigger spending cuts, reinvesting in these services may, alongside wider benefits for child development, contribute to reducing inequalities in childhood obesity.
Brief intervention using the PaperWeight Armband to identify older people at risk of undernutrition in the community: a preliminary evaluation
Authors: Edwards Steven , Farrer Kirstine , Rose Emma , Haynes David , McLaughlin John 
Published: June 2021

BackgroundThe risk of undernutrition in older adults in the community is high, with clear negative impacts on health and well-being. Nutritional screening is not routine and undernutrition often goes unrecognised. A community-level population public health intervention has the potential to target environments where the risk of undernutrition is highest. A programme has been established locally using the PaperWeight Armband as a simple nutritional screening tool in residents over 65 years, followed by supporting advice and community interventions. We undertook a nested pilot cohort evaluation within the wider programme to assess whether this could impact positively.MethodsParticipants found to be at risk of undernutrition in the programme were recruited consecutively. Baseline weight and other descriptors including accommodation and frailty were recorded, and then again at 12 weeks.Results83 participants were recruited from a wide variety of community settings, age range 65–99 years; 75% were women. Sixty-seven recruits were followed up for 12-week review. Of these, 54 (81%) had a positive outcome, recording either weight gain (66%) or no weight loss (15%) at 12 weeks. Benefit was seen in all living circumstances but was least evident in the frailest participants.ConclusionThe intervention is associated with positive outcomes, with reduction or stabilisation of nutritional risk in the majority of participants studied. The intervention can be delivered in a wide range of settings and does not require healthcare professions for the screening. Longer and larger studies are now required to study the health, well-being and socioeconomic impacts of the intervention in depth.
Serratus anterior plane versus paravertebral nerve blocks for postoperative analgesia after non-mastectomy breast surgery: a randomized controlled non-inferiority trial
Authors: Gabriel Rodney A , Swisher Matthew W , Sztain Jacklynn F , Curran Brian P , Said Engy T , Abramson Wendy B , Khatibi Bahareh , Alexander Brenton S , Finneran John J , Wallace Anne M , Armani Ava , Blair Sarah , Dobke Marek , Suliman Ahmed , Reid Christopher , Donohue Michael C , Ilfeld Brian M 
Published: June 2021

Background
Paravertebral and serratus plane blocks are both used to treat pain following breast surgery. However, it remains unknown if the newer serratus block provides comparable analgesia to the decades-old paravertebral technique.

Methods
Subjects undergoing unilateral or bilateral non-mastectomy breast surgery were randomized to a single-injection serratus or paravertebral block in a subject-masked fashion (ropivacaine 0.5%; 20 mL unilateral; 16 mL/side bilateral). We hypothesized that (1) analgesia would be non-inferior in the recovery room with serratus blocks (measurement: Numeric Rating Scale), and (2) opioid consumption would be non-inferior with serratus blocks in the operating and recovery rooms. In order to claim that serratus blocks are non-inferior to paravertebral blocks, both hypotheses must be at least non-inferior.

Results
Within the recovery room, pain scores for participants with serratus blocks (n=49) had a median (IQR) of 4.0 (0–5.5) vs 0 (0–3.0) for those with paravertebral blocks (n=51): 0.95% CI −3.00 to −0.00; p=0.001. However, the difference in morphine equivalents did not reach statistical significance for superiority with the serratus group consuming 14 mg (10–19) vs 10 mg (10–16) for the paravertebral group: 95% CI −4.50 to 0.00, p=0.123. Since the 95% CI lower limit of −4.5 was less than our prespecified margin of −2.0, we failed to conclude non-inferiority of the serratus block with regard to opioid consumption.

Conclusions
Serratus blocks provided inferior analgesia compared with paravertebral blocks. Without a dramatic improvement in safety profile for serratus blocks, it appears that paravertebral blocks are superior to serratus blocks for postoperative analgesia after non-mastectomy breast surgery.

Trial registration number

NCT03860974
.
Differential Effect of Graft-versus-Host Disease on Survival in Acute Leukemia according to Donor Type
Authors: Konuma Takaaki , Kanda Junya , Kuwatsuka Yachiyo , Yanada Masamitsu , Kondo Tadakazu , Hirabayashi Shigeki , Kako Shinichi , Akahoshi Yu , Uchida Naoyuki , Doki Noriko , Ozawa Yukiyasu , Tanaka Masatsugu , Eto Tetsuya , Sawa Masashi , Yoshioka Satoshi , Kimura Takafumi , Kanda Yoshinobu , Fukuda Takahiro , Atsuta Yoshiko , Kimura Fumihiko 
Published: June 2021

Abstract

Purpose:
The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source.

Experimental Design:
We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)].

Results:
The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I–II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P &lt; 0.001), overall mortality (OM; P &lt; 0.001), relapse (P &lt; 0.001), and non-relapse mortality (NRM; P &lt; 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure (P &lt; 0.001), OM (P &lt; 0.001), and NRM (P &lt; 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status.

Conclusions:
These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.
Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma
Authors: Burgener Justin M. , Zou Jinfeng , Zhao Zhen , Zheng Yangqiao , Shen Shu Yi , Huang Shao Hui , Keshavarzi Sareh , Xu Wei , Liu Fei-Fei , Liu Geoffrey , Waldron John N. , Weinreb Ilan , Spreafico Anna , Siu Lillian L. , de Almeida John R. , Goldstein David P. , Hoffman Michael M. , De Carvalho Daniel D. , Bratman Scott V. 
Published: June 2021

AbstractPurpose:Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation.Experimental Design:We conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I–IVA human papillomavirus–negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls.Results:CAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated (r &gt; 0.85). Patients with detectable pretreatment ctDNA by both methods demonstrated significantly worse overall survival (HR = 7.5; P = 0.025) independent of clinical stage, with lack of ctDNA clearance post-treatment strongly correlating with recurrence. We further leveraged cfMeDIP-seq profiles to validate a prognostic signature identified from TCGA samples.Conclusions:Tumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications.
Radiopotentiation Profiling of Multiple Inhibitors of the DNA Damage Response for Early Clinical Development
Authors: Gill Sonja J. , Wijnhoven Paul W.G. , Fok Jacqueline H.L. , Lloyd Rebecca L. , Cairns Jonathan , Armenia Joshua , Nikkilä Jenni , Lau Alan , Bakkenist Christopher J. , Galbraith Susan M. , Vens Conchita , O'Connor Mark J. 
Published: June 2021

Abstract
Radiotherapy is an effective anticancer treatment, but combinations with targeted agents that maximize efficacy while sparing normal tissue are needed. Here, we assess the radiopotentiation profiles of DNA damage response inhibitors (DDRi) olaparib (PARP1/2), ceralasertib (ATR), adavosertib (WEE1), AZD0156 (ATM), and KU-60648 (DNA-PK). We performed a radiotherapy combination screen and assessed how drug concentration and cellular DDR deficiencies influence the radiopotentiation ability of DDRi. We pre-selected six lung cancer cell lines with different genetic/signaling aberrations (including mutations in TP53 and ATM) and assessed multiple concentrations of DDRi in combination with a fixed radiotherapy dose by clonogenic assay. The effective concentration of DDRi in radiotherapy combinations is lower than that required for single-agent efficacy. This has the potential to be exploited further in the context of DDR deficiencies to increase therapeutic index and we demonstrate that low concentrations of AZD0156 preferentially sensitized p53-deficient cells. Moreover, testing multiple concentrations of DDRi in radiotherapy combinations indicated that olaparib, ceralasertib, and adavosertib have a desirable safety profile showing moderate increases in radiotherapy dose enhancement with increasing inhibitor concentration. Small increases in concentration of AZD0156 and particularly KU-60648, however, result in steep increases in dose enhancement. Radiopotentiation profiling can inform on effective drug doses required for radiosensitization in relation to biomarkers, providing an opportunity to increase therapeutic index. Moreover, multiple concentration testing demonstrates a relationship between drug concentration and radiotherapy effect that provides valuable insights that, with future in vivo validation, can guide dose-escalation strategies in clinical trials.
TPX-0131, a Potent CNS-penetrant, Next-generation Inhibitor of Wild-type ALK and ALK-resistant Mutations
Authors: Murray Brion W. , Zhai Dayong , Deng Wei , Zhang Xin , Ung Jane , Nguyen Vivian , Zhang Han , Barrera Maria , Parra Ana , Cowell Jessica , Lee Dong J. , Aloysius Herve , Rogers Evan 
Published: June 2021

Abstract

Since 2011, with the approval of crizotinib and subsequent approval of four additional targeted therapies, anaplastic lymphoma kinase (ALK) inhibitors have become important treatments for a subset of patients with lung cancer. Each generation of ALK inhibitor showed improvements in terms of central nervous system (CNS) penetration and potency against wild-type (WT) ALK, yet a key continued limitation is their susceptibility to resistance from ALK active-site mutations. The solvent front mutation (G1202R) and gatekeeper mutation (L1196M) are major resistance mechanisms to the first two generations of inhibitors while patients treated with the third-generation ALK inhibitor lorlatinib often experience progressive disease with multiple mutations on the same allele (mutations in cis, compound mutations). TPX-0131 is a compact macrocyclic molecule designed to fit within the ATP-binding boundary to inhibit ALK fusion proteins. In cellular assays, TPX-0131 was more potent than all five approved ALK inhibitors against WT ALK and many types of ALK resistance mutations, e.g., G1202R, L1196M, and compound mutations. In biochemical assays, TPX-0131 potently inhibited (IC50 &lt;10 nmol/L) WT ALK and 26 ALK mutants (single and compound mutations). TPX-0131, but not lorlatinib, caused complete tumor regression in ALK (G1202R) and ALK compound mutation-dependent xenograft models. Following repeat oral administration of TPX-0131 to rats, brain levels of TPX-0131 were approximately 66% of those observed in plasma. Taken together, preclinical studies show that TPX-0131 is a CNS-penetrant, next-generation ALK inhibitor that has potency against WT ALK and a spectrum of acquired resistance mutations, especially the G1202R solvent front mutation and compound mutations, for which there are currently no effective therapies.
Improving Efficiency of the Barbershop Model of Hypertension Care for Black Men With Virtual Visits
Authors: Blyler Ciantel A. , Ebinger Joseph , Rashid Mohamad , Moy Norma P. , Cheng Susan , Albert Christine M. , Rader Florian 
Published: June 2021

Background
The LABBPS (Los Angeles Barbershop Blood Pressure Study) developed a new model of hypertension care for non‐Hispanic Black men that links health promotion by barbers to medication management by pharmacists. Barriers to scaling the model include inefficiencies that contribute to the cost of the intervention, most notably, pharmacist travel time. To address this, we tested whether virtual visits could be substituted for in‐person visits after blood pressure (BP) control was achieved.

Methods and Results

We enrolled 10 Black male patrons with systolic BP ≥140 mm Hg into a proof‐of‐concept study in which barbers promoted follow‐up with pharmacists who initially met each patron in the barbershop, where they prescribed BP medication under a collaborative practice agreement with the patrons' physician. Medications were titrated during bimonthly in‐person visits to achieve a BP goal of ≤130/80 mm Hg. Once BP goal was reached, visits were done by videoconference. Final BP and safety outcomes were assessed at 12 months. Nine patients completed the intervention. Baseline BP of 155±14/83.9±11 mm Hg decreased by −28.7±13/−8.9±15 mm Hg (
P
<0.0001). These data are statistically indistinguishable from prior LABBPS data (
P
=0.8 for change in systolic BP and diastolic BP). Hypertension control (≤130/80 mm Hg) was 67% (6 of 9), numerically greater than the 63% observed in LABBPS (
P
=not significant). As intended, the mean number of in‐person visits decreased from 11 in LABBPS to 6.6 visits over 12 months. No treatment‐related serious adverse events occurred.

Conclusions
Virtual visits represent a viable substitute for in‐person visits, both improving pharmacist efficiency and reducing cost while preserving intervention potency.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT 03726710.
Cognitive Metaphor Theory Integrated into Comparative Theology
Authors: Remias Yesudasan 
Published: June 2021

Abstract
The emergence of the new comparative theology in the west has greatly benefitted from Indian Vedic texts and related ones. Despite their extensive use for western theological reflection, comparative theology, however, has not come to the limelight in India, since most of the western initiatives have been perceived to be camouflaged missionary efforts. This paper proposes the cognitive metaphor theory as a fitting supplement to comparative theology. I argue that combining both has much to offer to study, learn, and relate religions in the multi-religiously coexisting context of India. I explore its possibilities and challenges and address how new comparative theology stays distinct from its nineteenth-century efforts in terms of bridging religious traditions by learning from them. This paper draws much from my own experiences, insights, and studies as a native of Indian culture, brought up in Christian tradition. My studies and researches are focused on comparative theology developed through the lens of cognitive metaphor theory.