bluuebunny/crossref_metadata_2025_split huggingface dataset:
Menthol-Based Topical Analgesic Induces Similar Upper and Lower Body Pain Pressure Threshold Values: A Randomized Trial
Authors: Behm David G. , Herat Nehara , Power Gerard M.J. , Brosky Joseph A. , Page Phil , Alizadeh Shahab 
Published: September 2021

Context: Both health professionals and consumers use menthol-based topical analgesics extensively for the temporary relief of pain from musculoskeletal ailments or injury. However, there are no reports of differences in the pain pressure threshold (PPT) or the relative effectiveness of topical analgesics to reduce pain in the upper and lower body muscles and tendons. The objective of this study was to investigate whether differences existed in PPT and relative pain attenuation associated with a menthol-based topical analgesic over a variety of upper and lower body muscles and tendons. Design: Randomized allocation, controlled, intervention study. Methods: Sixteen participants (10 females and 6 males) were tested on their dominant or nondominant side. The order of specific muscle/tendon testing was also randomized, which included upper body (middle deltoid, biceps brachii, and lateral epicondylar tendon) and lower body locations (quadriceps, hamstrings, gastrocnemius, lumbosacral erector spinae muscles, and patellar and Achilles tendons). The PPT was monitored before and 15 minutes following the application of a menthol-based topical analgesic. Results: A menthol-based topical analgesic increased PPT (decreased pain sensitivity) overall (P = .05; 11.6% [2.4%]; d = 1.05) and PPT was higher (P < .0001; 31.5%–44.2%; d = 1.03–1.8) for lower versus upper body locations. Conclusions: Health professionals and the public can be assured of similar reductions in pain sensitivity independent of the location of application of a menthol-based topical analgesic.
Implementation of an adapted Sepsis Risk Calculator algorithm to reduce antibiotic usage in the management of early onset neonatal sepsis: a multicentre initiative in Wales, UK
Authors: Goel Nitin , Cannell Stephanie , Davies Gemma , Natti Murali Sridhar , Kirupaalar Vickness , Abelian Artur , Saeed Shakir , Smith Rhian , Manikonda Ravi , Pitchaikani Prem Kumar , Davies Dawn , Morris Rachel May , Edwards Lynsey , Govindaraju Roopashree , Creese Kate , Jones Jane , Choudhary Jalil , Rowley Sarah , Sethuraman Chidambaram , Muxworthy Helen , Curtis Felicity , Donnelly Patricia , Joishy Manohar , Barnard Ian , Kenny Celyn , Pal Rajarshi , Jones Karen , Banerjee Sujoy 
Published: September 2021

ObjectiveAssess the impact of introducing a consensus guideline incorporating an adapted Sepsis Risk Calculator (SRC) algorithm, in the management of early onset neonatal sepsis (EONS), on antibiotic usage and patient safety.DesignMulticentre prospective studySettingTen perinatal hospitals in Wales, UK.PatientsAll live births ≥34 weeks’ gestation over a 12-month period (April 2019–March 2020) compared with infants in the preceding 15-month period (January 2018–March 2019) as a baseline.MethodsThe consensus guideline was introduced in clinical practice on 1 April 2019. It incorporated a modified SRC algorithm, enhanced in-hospital surveillance, ongoing quality assurance, standardised staff training and parent education. The main outcome measure was antibiotic usage/1000 live births, balancing this with analysis of harm from delayed diagnosis and treatment, disease severity and readmissions from true sepsis. Outcome measures were analysed using statistical process control charts.Main outcome measuresProportion of antibiotic use in infants ≥34 weeks’ gestation.Results4304 (14.3%) of the 30 105 live-born infants received antibiotics in the baseline period compared with 1917 (7.7%) of 24 749 infants in the intervention period (45.5% mean reduction). All 19 infants with culture-positive sepsis in the postimplementation phase were identified and treated appropriately. There were no increases in sepsis-related neonatal unit admissions, disease morbidity and late readmissions.ConclusionsThis multicentre study provides evidence that a judicious adaptation of the SRC incorporating enhanced surveillance can be safely introduced in the National Health Service and is effective in reducing antibiotic use for EONS without increasing morbidity and mortality.
Maternal vitamin B12, folate during pregnancy and neurocognitive outcomes in young adults of the Pune Maternal Nutrition Study (PMNS) prospective birth cohort: study protocol
Authors: Behere Rishikesh V , Deshpande Gopikrishna , Bandyopadhyay Souvik Kumar , Yajnik Chittaranjan 
Published: September 2021

IntroductionThe Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that intrauterine and early life exposures significantly influence fetal development and risk for disease in later life. Evidence from prospective birth cohorts suggests a role for maternal B12and folate in influencing neurocognitive outcomes in the offspring. In the Indian setting, B12deficiency is common during the pregnancy while rates of folate deficiency are lower. The long-term influences of maternal nutrition during the pregnancy on adult neurocognitive outcomes have not been examined. The Pune Maternal Nutrition Study (PMNS) is a preconceptional birth cohort into its 24th year and is considered a unique resource to study the DOHaD hypothesis. We found an association between maternal B12status in pregnancy and child’s neurocognitive status at 9 years of age. We now plan to assess neurocognitive function and MRI measurements of brain structural–functional connectivity at young adult age to study its association with maternal nutritional exposures during the pregnancy.Methods and analysisAs part of ongoing prospective follow-up in young adults of the PMNS at the Diabetes Unit, KEM Hospital Research Center, Pune India, the following measurements will be done: neurocognitive performance (Standardised Tests of Intelligence, Verbal and Visual Memory, Attention and Executive Functions), temperament (Adult Temperament Questionnaire), psychopathology (Brief Symptom Inventory and Clinical Interview on Mini Neuropsychiatric Interview 7.0). Brain MRI for structural T1, resting-state functional connectivity and diffusion tensor imaging will be performed on a subset of the cohort (selected based on exposure to a lower or higher maternal B12status at 18 weeks of pregnancy).Ethics and disseminationThe study is approved by Institutional ethics committee of KEM Hospital Research Center, Pune. The results will be shared at national and international scientific conferences and published in peer-reviewed scientific journals.Trial registration numberNCT03096028
Influence of COVID-19 on the preventive health behaviours of Indigenous Peoples of Australia residing in New South Wales: a mixed-method study protocol
Authors: Usher Kim , Bhullar Navjot , Sibbritt David , Anubha Amarasena Suruchi Sue , Peng Wenbo , Durkin Joanne , Smallwood Reakeeta , Power Tamara , Porter Cheryl , McGowen Debbie , Jackson Debra 
Published: September 2021

IntroductionChronic conditions impact Indigenous Peoples of Australia at a much higher rate than non-Indigenous Australians. Attendance at the Medicare Benefits Scheme (MBS) supported Indigenous health checks are crucial to improve prevention and management of chronic health conditions. However, in conjunction with lifestyle and environmental factors, attendance rates at primary healthcare services for screening and treatment have fallen in Australia during the COVID-19 pandemic. This study aims to explore the influence of the COVID-19 pandemic on preventive health behaviours of Indigenous Australians and the associated barriers to, and enablers of, engagement with health services to formulate a targeted intervention strategy.Methods and analysisA concurrent mixed-methods study (comprising quantitative and qualitative data collection methods) will be employed. Descriptive analysis of MBS data about the characteristics of Indigenous Peoples of Australia claiming health assessment services will be performed. Generalised estimating equation regression models will be used to examine the use of health assessment services over time. Qualitative interviews informed by Indigenous research methods will be conducted. Interviews will investigate barriers to, and enablers of, engagement with health services. Thematic approach guided by the principles of indigenist praxis, storytelling and collaborative research will be used to analyse the interview data. The project commenced in July 2020 and will be completed by July 2022.Ethics and disseminationThe project received ethics approval from the Aboriginal Health and Medical Research Council of New South Wales and the University of New England Human Research Ethics Committee. Findings will be disseminated via peer-reviewed journal articles, conferences, government and relevant stakeholder reports, and infographics.
A long and winding road: non-traditional routes into medical leadership
Authors: Gulati Steve , Shrimpton Christiane 
Published: September 2021

IntroductionClinicians enter the medical profession through a variety of routes. This paper explores how non-traditional routes into the medical profession can follow through into subsequent medical leadership practice, influencing issues of confidence, self-image and assumptions about leadership as a concept.MethodThe first-person reflections of a doctor who entered the profession and the National Health Service from the German system and with a non-standard background are considered. We then discuss how those involved in leadership education can use diversity as a developmental tool. The article starts and ends with personal reflections and observations from a Consultant Opthalmologist, interposed with insights from the pedagogy of leadership development by a University academic.ConclusionsWe conclude that medical leadership development can be enriched through recognising the value that non-traditional routes in clinical leadership can bring, and that educators can use the leverage of difference and diversity to create positive loops of development activity.
Trajectories of opioid consumption from day of surgery to 28 days postoperatively: a prospective cohort study in patients undergoing abdominal, joint, or spine surgery
Authors: McCarthy Robert J , Adams Ashley Meng , Sremac Amanda C , Kreider Wendy Jo , Pelletier Pete L , Buvanendran Asokumar 
Published: September 2021

IntroductionDescriptions of opioid use trajectories and their association with postsurgical pain and opioid consumption are limited. We hypothesized that trajectories of opioid consumption in the first 28 days following surgery would be associated with unique patterns of pain and duration of opioid use.MethodsA prospective longitudinal cohort of patients undergoing elective inpatient abdominal, joint, or spine surgery between June 2016 and June 2019 was studied. At hospital discharge and every 7 days for 28 days, patients were assessed for pain, analgesic use, pain interference, satisfaction, and side effects. Duration of opioid use was determined for 6 months. The primary analysis used latent class group modeling to identify trajectories of opioid use.ResultsDecreasing, high, and persistent opioid trajectories were identified following joint and spine surgery and a decreasing and persistent trajectory following abdominal surgery. Reported pain was greater in the high and persistent trajectories compared with the decreasing use trajectories. Compared with the decreasing opioid trajectory, the median duration of opioid use was increased by 4.5 (95% CI 1 to 22, p<0.01) weeks in persistent opioid use abdominal and by 6 (95% CI 0 to 6, p<0.01) weeks in the high or persistent use joint and spine groups. The odds (95% CI) of opioid use at 6 months in the high or persistent opioid use trajectory was 24.3 (2.9 to 203.4) for abdominal and 3.7 (1.9 to 7.0) for joint or spine surgery compared with the decreasing use trajectory. Morphine milliequivalent per 24 hours of hospitalization was the primary independent predictor of opioid use trajectories.ConclusionsWe observed distinct opioid use trajectories following abdominal and joint or spine surgery that were associated with different patterns of pain and duration of opioid use postoperatively. Prediction of postoperative opioid use trajectory groups may be clinically important for identifying risk of prolonged opioid use.
Critical insights in laboratory shear wave velocity correlations of clays
Authors: Elbeggo Dania , Ethier Yannic , Dubé Jean-Sébastien , Karray Mourad 
Published: September 2021

Shear wave velocity, Vs, is an important mechanical–dynamic parameter allowing the characterization of a soil in the elastic range (γ < 10–3%). Thirty-five existing Gmax or Vs laboratory correlations were examined in this study and are grouped into different general forms based on their geotechnical properties. A database of 11 eastern Canadian clay deposits was selected and used for the critical insights. The effect of the coefficient of earth pressure at rest, K0, was also examined. A range of variation for each general form of correlation was determined to take the plasticity index and void ratio values of investigated sites into account. The analysis shows a significant scatter in Vs1 values predicted by existing correlations and raises questions on the applicability of these correlations, especially for eastern Canadian clays. New correlations are proposed for Champlain clays based on laboratory measurement of Vs using the piezoelectric ring-actuator technique, P-RAT, incorporated in consolidation cells. An analysis of P-RAT results reveals the sample disturbance effect and suggests an approach to correct the effect of disturbance on laboratory Vs measurements. The applicability of the proposed correlations, including the disturbance correction, is validated by comparison with in situ measurements using multi-modal analysis of surface waves (MMASW).
Soft Group Action From Classical View Point
Authors: Goldar Sujay 
Published: September 2021

Soft set theory, proposed by Molodtsov, Soft set theory — First results, Computers and Mathematics with Applications 37(4/5) (1999) 19–31, has been regarded as an effective mathematical tool to deal with uncertainties. In this paper, we introduce the notion of the soft group action as a general group action and study their properties. Some interesting results and relation between soft group action and ordinary group action are studied. Also, Soft Stabilizer, Soft Centralizer and Soft Normalizer have been depicted.
Declarative Power Sequencing
Authors: Schult Jasmin , Schwyn Daniel , Giardino Michael , Cock David , Achermann Reto , Roscoe Timothy 
Published: September 2021

Modern computer server systems are increasingly managed at a low level by baseboard management controllers (BMCs). BMCs are processors with access to the most critical parts of the platform, below the level of OS or hypervisor, including control over power delivery to every system component. Buggy or poorly designed BMC software not only poses a security threat to a machine, it can permanently render the hardware inoperative. Despite this, there is little published work on how to rigorously engineer the power management functionality of BMCs so as to prevent this happening.
This article takes a first step toward putting BMC software on a sound footing by specifying the hardware environment and the constraints necessary for safe and correct operation. This is best accomplished through automation: correct-by-construction power control sequences can be efficiently generated from a simple, trustworthy model of the platform’s power tree that incorporates the sequencing requirements and safe voltage ranges of all components.
We present both a modeling language for complex power-delivery networks and a tool to automatically generate safe, efficient power sequences for complex modern platforms. This not only increases the trustworthiness of a hitherto opaque yet critical element of platform firmware: regulator and chip power models are significantly simpler to produce than hand-written power sequences. This, combined with model reuse for common components, reduces both time and cost associated with platform bring-up for new hardware.
We evaluate our tool using a new high-performance 2-socket server platform with >100W per socket TDP, tight voltage limits and 25 distinct power regulators needing configuration, showing both fast (<10s) tool runtime, and correct power sequencing of a live system.
Two Different Upper Tract Urological Malignancies on Either Side
Authors: De Silva W. S. L. , De Almeida S. R. , Karunarathne G. D. B. J. , Samarathunga A. A. S. , Gannoruwa K. M. C. S. , Jayasundara J. A. S. B. 
Published: September 2021

Introduction. The genitourinary system is a recognized site for multiple primary malignant neoplasms even without syndromic anomalies. However, to the best of our knowledge, a case of upper tract urothelial carcinoma (UTUC) with contralateral renal cell carcinoma (RCC) is not reported in surgical literature so far. Case Presentation. A 52-year-old Sri Lankan male patient was found to have a right lower ureteric tumour and a left renal mass together upon investigating for painless visible hematuria. The right ureteric tumour measured

32
×
22

mm

resulting in moderate hydronephrosis and cortical thinning of the right kidney, and the left renal mass measured

43
×
38

mm

involving the lower pole. The biopsy of the right ureteric lesion revealed a high-grade transitional cell carcinoma with focal nested pattern and that of the left renal mass revealed a clear cell carcinoma. Right nephroureterectomy followed by a left partial nephrectomy was performed in six weeks’ interval. The histology of both the resected specimens confirmed the biopsy findings. Discussion. A high-risk upper tract urothelial carcinoma such as the right ureteric tumour of this patient required a nephroureterectomy which makes the management of the contralateral renal cell carcinoma more complex. An adequate functional renal remnant was ensured after offering oncologically sound surgical treatment for both the malignancies of this patient. Conclusion. A UTUC when associated with a contralateral RCC poses challenges in patient management. The preservation of renal excretory function has to be considered as an important determinant in addition to oncologically sound surgical resection when managing complex cases of genitourinary malignancies involving both sides of the upper urinary tract.
FSTL1 Secreted by Activated Fibroblasts Promotes Hepatocellular Carcinoma Metastasis and Stemness
Authors: Loh Jia-Jian , Li Tsz-Wai , Zhou Lei , Wong Tin-Lok , Liu Xue , Ma Victor W.S. , Lo Chung-Mau , Man Kwan , Lee Terence K. , Ning Wen , Tong Man , Ma Stephanie 
Published: September 2021

Abstract

The tumor microenvironment plays a critical role in maintaining the immature phenotype of tumor-initiating cells (TIC) to promote cancer. Hepatocellular carcinoma (HCC) is a unique disease in that it develops in the setting of fibrosis and cirrhosis. This pathologic state commonly shows an enrichment of stromal myofibroblasts, which constitute the bulk of the tumor microenvironment and contribute to disease progression. Follistatin-like 1 (FSTL1) has been widely reported as a proinflammatory mediator in different fibrosis-related and inflammatory diseases. Here we show FSTL1 expression to be closely correlated with activated fibroblasts and to be elevated in regenerative, fibrotic, and disease liver states in various mouse models. Consistently, FSTL1 lineage cells gave rise to myofibroblasts in a CCL4-induced hepatic fibrosis mouse model. Clinically, high FSTL1 in fibroblast activation protein–positive (FAP+) fibroblasts were significantly correlated with more advanced tumors in patients with HCC. Although FSTL1 was expressed in primary fibroblasts derived from patients with HCC, it was barely detectable in HCC cell lines. Functional investigations revealed that treatment of HCC cells and patient-derived 3D organoids with recombinant FSTL1 or with conditioned medium collected from hepatic stellate cells or from cells overexpressing FSTL1 could promote HCC growth and metastasis. FSTL1 bound to TLR4 receptor, resulting in activation of AKT/mTOR/4EBP1 signaling. In a preclinical mouse model, blockade of FSTL1 mitigated HCC malignancy and metastasis, sensitized HCC tumors to sorafenib, prolonged survival, and eradicated the TIC subset. Collectively, these data suggest that FSTL1 may serve as an important novel diagnostic/prognostic biomarker and therapeutic target in HCC.

Significance:
This study shows that FSTL1 secreted by activated fibroblasts in the liver microenvironment augments hepatocellular carcinoma malignancy, providing a potential new strategy to improve treatment of this aggressive disease.
Clinical Trials Assessing Hypomethylating Agents Combined with Other Therapies: Causes for Failure and Potential Solutions
Authors: Zavras Phaedon D. , Shastri Aditi , Goldfinger Mendel , Verma Amit K. , Saunthararajah Yogen 
Published: September 2021

Abstract

Purpose:
Azacitidine and decitabine are hypomethylating agents (HMA), that is, both inhibit and deplete DNA methyltransferase 1 (DNMT1). HMAs are standard single-agent therapies for myelodysplastic syndromes and acute myelogenous leukemias. Several attempts to improve outcomes by combining HMAs with investigational agents, excepting with the BCL2-inhibitor venetoclax, have failed in randomized clinical trial (RCT) evaluations. We extract lessons from decades of clinical trials to thereby inform future work.

Experimental Design:
Serial single-agent clinical trials were analyzed for mechanism and pathway properties of HMAs underpinning their success, and for rules for dose and schedule selection. RCTs were studied for principles, dos and don'ts for productive combination therapy.

Results:
Single-agent HMA trial results encourage dose and schedule selection to increase S-phase–dependent DNMT1 targeting, and discourage doses that cause indiscriminate antimetabolite effects/cytotoxicity, because these attrit myelopoiesis reserves needed for clinical response. Treatment-related myelosuppression should prompt dose/frequency reductions of less active investigational agents rather than more active HMA. Administering cytostatic agents concurrently with HMA can antagonize S-phase–dependent DNMT1 targeting. Supportive care that enables on-time administration of S-phase (exposure-time)–dependent HMA could be useful. Agents that manipulate pyrimidine metabolism to increase HMA pro-drug processing into DNMT1-depleting nucleotide, and/or inhibit other epigenetic enzymes implicated in oncogenic silencing of lineage differentiation, could be productive, but doses and schedules should adhere to therapeutic index/molecular–targeted principles already learned.

Conclusions:
More than 40 years of clinical trial history indicates mechanism, pathway, and therapeutic index properties of HMAs that underpin their almost exclusive success and teaches lessons for selection and design of combinations aiming to build on this treatment foundation.
Individualism during Crises
Authors: Bian Bo , Li Jingjing , Xu Ting , Foutz Natasha Z. 
Published: September 2021

Abstract
Individualism has long been linked to economic growth. Using the COVID-19 pandemic, we show that such a culture can hamper the economy's response to crises, a period with heightened coordination frictions. Exploiting variation in U.S. counties' frontier experience, we show that more individualistic counties engage less in social distancing and charitable transfers and are less willing to receive COVID-19 vaccines. The effect of individualism is stronger where social distancing has higher externality and holds at the individual level when we exploit migrants for identification. Our results suggest that individualism can exacerbate collective action problems during economic downturns.