bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Lipid-Lowering Therapy in Patients Who Were Functionally Deferred Percutaneous Coronary Intervention
Authors: Abe Takuro , Shimazaki Kensuke , Moriyama Tetsu , Murohashi Akira , Iwanami Yuji , Sasaki Akihito , Saito Katsumi , Jujo Kentaro
Published: February 2022

Background
Deferral of percutaneous coronary intervention (PCI) for functionally insignificant stenosis, defined as fractional flow reserve (FFR) > 0.80, is associated with favorable long-term prognoses. The lower-the-better strategy for low-density lipoprotein cholesterol (LDL-C) management is an established non-angioplasty therapy to improve the clinical outcomes of patients undergoing PCI. We examined the optimal LDL-C management in cases of intermediate coronary stenosis with deferred PCI on the basis of FFR values.
Methods
This observational study included 273 consecutive patients with a single target vessel and deferred PCI with an FFR > 0.80. Patients with an FFR of 0.81–0.85 (n = 93) and those with FFR > 0.85 (n = 180) were classified into the lower (< 100 mg/dL) and higher (≥ 100 mg/dL) LDL-C groups. The endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, non-fatal myocardial infarction, ischemic stroke, heart failure hospitalization, and unplanned revascularization.
Results
Patients with an FFR of 0.81–0.85 had a significantly higher MACCE rate than those with an FFR > 0.85 (log-rank, p = 0.003). In patients with an FFR of 0.81–0.85, the lower LDL-C group showed a significantly lower MACCE rate than the higher LDL-C group (log-rank, p = 0.006). However, the event rate did not differ significantly between the two groups in patients with FFR > 0.85 (log-rank, p = 0.84).
Conclusions
Uncontrolled LDL-C levels were associated with higher MACCE rates in cases with deferred PCI due to an FFR of 0.81–0.85. This high-risk population for adverse cardiovascular events should receive strict LDL-C-lowering therapy.
Superconductivity at 50 K of a Coordination Polymer System
Authors: Xu Zhengtao , He Jun , Liu Zhiqing , Tang Liangming , Ye Xinhe , Hu Jieying
Published: February 2022

The synthesis of coordination polymers (e.g., Prussian blue) is as old as modern chemistry, but never stops surprising people. Underlying this rich chemistry is the infinite organic molecules that can be designed to link up various metal ions or clusters. We here report superconductivity observed of a designer coordination polymer system sporting the chemically soft mercaptan and hard carboxyl groups. The mercaptan-carboxyl (dubbed Mercarb, or QiuSuo in Mandarin Pinyin) synergy smacks of Daoism and here carries over from the molecular to the solid state: the soft sulfur donors bond with Co2+/Ni2+ (or other transition metal ions) to afford 2D sheets for charge transport, while the interlayer metal-carboxylate domain is more ionic and mediates the transition into the superconductive state. Besides the flexible QiuSuo design, this CP system is open, and allows exchange of molecule guests for tuning the electron-hole balance, in order to achieve high-temperature superconductivity.
BRD4 inhibition by JQ1 protects against LPS-Induced Cardiac Dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes
Authors: Li wenjun , Shen XiuFeng , Feng Shenglan , Liu Yue , Zhao Huiying , Zhou Guohao , Sang Ming , Sun Xiaodong , Jiao Rong , Liu Fuyuan
Published: February 2022

JQ1, a BRD4 protein inhibitor, first identified because of its therapeutic role in cancer, has gradually demonstrated a protective effect on the heart in recent years; however, it is unclear whether JQ1 also plays a role in LPS-induced cardiac dysfunction. This paper aims to investigate the effects of the BRD4 inhibitor JQ1 on LPS-induced cardiac dysfunction and its mechanism. In the experiments, we found that BRD4 was significantly upregulated in the hearts of LPS-treated mice.JQ1 treatment improved survival and cardiac function in LPS-treated mice and reduced cardiomyopathologic injury, inflammation, and oxidative injury.JQ1 treatment similarly reduced the release of lactate dehydrogenase and inflammatory factors in H9C2 cells treated with LPS.JQ1 significantly upregulated silent information regulator 1 (SIRT1) expression and suppressed the upregulation of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and GSDMD in heart tissues induced by LPS.Meanwhile, we obtained the same results in H9C2 cells treated with LPS. The administration of the SIRT1 inhibitor (EX527) intervention partially blocked the JQ1-mediated downregulation of NLRP3, cleaved caspase-1, GSDMD in LPS-induced H9C2 cells. Therefore, we propose that JQ1 can improve LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes, which may be a promising strategy for treating sepsis cardiomyopathy.
Sample Size Calculation for Prevalence Studies Using Scalex and ScalaR Calculators
Authors: NAING Lin , NORDIN Rusli , RAHMAN Hanif ABDUL , NAING Yuwadi Thein
Published: February 2022

Although books and articles guiding the methods of sample size calculation for prevalence studies are available, authors observe several issues related to sample size calculation in published articles such as incorrect calculation, incorrect use of formula, incorrect parameters, and incomplete sample size reporting. This brief article focuses on sample size calculation for a prevalence study, choosing correct parameters with proper understanding, and reporting issues, and demonstrate use of a well-prepared calculator which also assist users to make proper decision making and appropriate report. Two calculators can be used with free software (spreadsheet and RStudio) which benefit researchers with limited resources. The calculators are available at: (https://sites.google.com/view/sr-ln/ssc)
Artemisinin inhibits innate immune cell chemotaxis, cytokine production and NET release
Authors: Morad Hassan , Luqman Suaib , Pinto Larissa , Cunningham Kevin P. , Vilar Bruno , Clayton Georgia , Shankar-Hari Manu , McNaughton Peter A.
Published: February 2022

Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines. In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here we identify the antimalarial compound artemisinin as a potent and selective inhibitor of neutrophil and macrophage chemotaxis induced by many chemotactic agents. Artemisinin released calcium from intracellular stores in a similar way to thapsigargin, a known inhibitor of the Sarco/Endoplasmic Reticulum Calcium ATPase pump (SERCA), but unlike thapsigargin, artemisinin blocks only the SERCA3 isoform. Inhibition of SERCA3 by artemisinin was irreversible and was inhibited by iron chelation, suggesting iron-catalysed alkylation of a specific cysteine residue in SERCA3 as the mechanism by which artemisinin inhibits immune cell motility. In murine infection models, artemisinin potently suppressed immune cell invasion into both peritoneum and lung in vivo and inhibited the release of cytokines/chemokines and neutrophil extracellular traps (NETs). This work suggests that artemisinin may have value as a therapy in conditions such as sepsis and Covid-19 in which over-activation of the innate immune system causes tissue injury that can lead to death.
Applying the Omaha System to Determine Health Problems Among Child Workers: Example from a Suburb of Istanbul
Authors: Ornek Ozlem Koseoglu , Kolac Nurcan , ozdemir Saadet
Published: February 2022

Background: Education has important effects on the physical and psychosocial development of children. However, a high rate of children worldwide engaged in child labour, and a majority of them deprived of formal education opportunities due to work. Work conditions have a multifaceted, negative effect on children's health and quality of life. In this context, it was aimed to determine the physiological, psychosocial, and health-related behaviours, as well as the environmental problems of migrant and non-migrant child workers in lower-secondary schools in using the Omaha System Problem Classification Scheme, and to examine related factors. Method: This is descriptive-correlational and observational study. The sample was selected using a purposive sampling method. The study population comprised migrant and non-migrant child workers from two lower-secondary schools in suburb of Istanbul. Descriptive Characteristics Assessment Form and Nightingale Notes Software based on the terminology of the Omaha System were used for data collection.Results: The participants were 81 child workers aged 10–13 years, 86% of them were male. 12% of them were migrant from Syria. 85% worked to contribute their family income. The most common health problems were mental health, neglect, income, oral health, nutrition, personal care, physical activity, sleep and rest patterns, and neighbourhood/workplace safety. There was an association between mental health problems and family health status; between individual health status and oral health as well as role change; between maternal education level and oral health as well as personal care and between nutrition and paternal education level (p<.05).Conclusion: The Omaha system was found suitable for determining health problems of migrant and non-migrant juvenile labour. However, it is necessary to prevent poverty, develop the understanding of the social state, and comply with legal norms. We recommend that researchers examine the health of child workers in long-term and mixed-method observational studies.
Serological evidence of zoonotic filovirus exposure among bushmeat hunters in Guinea
Authors: Carroll Miles
Published: February 2022

Recent human Ebola virus (EBOV) outbreaks caused by persistent EBOV infection raised questions on the role of zoonotic spillover in filovirus epidemiology. To characterise potential historical filovirus zoonotic exposure, we collected cross-sectional serum samples from bushmeat hunters (n = 498) in Macenta Prefecture Guinea, adjacent to the index site of the 2013 EBOV-Makona spillover event. We identified distinct immune signatures (20/498, 4.0%) to multiple EBOV antigens (GP, NP, VP40) using a stepwise ELISA and Western blot analysis and, live EBOV neutralisation (5/20; 25%). Using comparative serological data from PCR-confirmed survivors of the 2013–2016 EBOV outbreak, we demonstrated that most signatures (15/20) were not plausibly explained by prior EBOV-Makona exposure. Subsequent data-driven modelling of EBOV immunological outcomes to remote-sensing environmental data also revealed consistent associations with intact closed canopy forest. Together our findings suggest past exposure to other closely related filoviruses prior to the 2013–2016 west African epidemic and highlight future surveillance priorities.
Utility of 3D printed models in acetabular fracture teaching for Orthopaedic trainees
Authors: Goyal Saumitra , Chua Chen Xi Kasia , Chen Yongsheng , Murphy Diarmuid , O’Neill Gavin Kane
Published: February 2022

Objective To evaluate the utility of 3-D printed models of acetabular fractures as a teaching and assessment tool compared to conventional lecture based teaching among orthopaedic trainees. MethodsThis was randomised prospective study conducted in a tertiary hospital setting which was consisted of 16 Orthopaedic residents. Ten different cases of acetabular fracture patterns were identified and printed as 3-D models. Baseline knowledge of acetabular fracture classification and surgical approach was determined by an x-ray based pre-test. Trainees were then randomly assigned into two groups. Group I received only lectures. Group II were additionally provided with 3-D printed models during the lecture. Participants then received a post-test and were assessed for comprehension and retention of teaching. ResultsSixteen trainees participated in the trial. Both Group 1 and Group 2 improved post teaching with mean score of 2.5 and 1.9 to 4.4 and 6 out of 10 respectively. Post test score for fracture classification and surgical approach were significantly higher for 3-D model group (p<0.05). Trainees felt physical characteristics of the 3-D models were good representation of acetabular fracture configuration, and should be used routinely for teaching and surgical planning. Conclusion3-D printed model of real clinical cases have significant educational impact compared to lecture based learning in improving young trainees understanding of complex acetabular fractures.
Intention to be screened following presentation of benefits and harms of breast cancer screening: a study of women’s views in 5 European countries
Authors: Ritchie David , Hal Guido Van , Broucke Stephan Van den
Published: February 2022

BackgroundThis study aimed to understand whether being informed about the awareness of benefits and harms of mammography screening impacts on the intention to be screened for breast cancer.MethodsA cross-sectional survey of women from five countries (Belgium, France, Italy, Spain, and the United Kingdom) was performed in January 2021. The survey contained items to measure cognitive variables from the theory of planned behaviour and health belief model and included the 6-item version of the European Health Literacy Survey Questionnaire (HLS-EU-Q6). ResultsA total of 1180 participants responded to the survey. 19.5% of participants (n=230) were able to correctly identify that mammography screening carries both benefits and harms. 56.9% of participants (n=672) responded that they would be more likely to participate in screening in the future after being informed about the benefits and harms of mammography screening. ConclusionsThe presentation of simple but accurate information about the benefits and harms of participation in mammography screening to women did not negatively impact upon intention to be screened. Screening programme managers should not be discouraged by the assumption of decreased participation through increasing efforts to address the lack of knowledge on benefits and harms.
The role of Emergency Medicine Interest Groups in the development of Emergency Medicine: A case of MUST-EMIG in Uganda
Authors: Kajjimu Jonathan , Odakha Justine Athieno , Makai Conrad , Kaginda Beneth Tusiime , Nakachwa Janat , Karungi Annet , Lubega Frank , Tukamuwebwa Jespa , Kakande Reagan , Lyon Mary Ellen , Tagg Andrew
Published: February 2022

BackgroundEmergency medicine (EM) is a new specialty in Uganda since 2017 which is currently actively engaged in improving its emergency care system. To build a strong emergency care system, it is important to have a critical mass of specially trained health professionals with the skillset and dedication to work in emergency departments. There is no current formal EM undergraduate curriculum and so most undergraduates do not get the chance to interact with the new specialists and to gain interest. The MUST-EMIG was established to bridge this gap. This study was done to assess the contribution of MUST-EMIG towards the development of this critical mass.Objectives1. Discover students' reasons for joining the Mbarara University of Science and Technology Emergency Medicine Interest Group (MUST-EMIG).2. Assess whether interest in learning emergency medicine was affected by participation in MUST-EMIG.3. Evaluate plans to pursue emergency medicine as a specialty before and after joining MUST-EMIG.4. Determine whether MUST-EMIG affected students’ perception of emergency medicine’s importance in Uganda’s health care system.5. Elicit feedback from students on their experience as members of MUST-EMIG. MethodsThe MUST-EMIG executive developed a membership survey which was reviewed by MUST-EMIG’s faculty advisor for suitability. Members of MUST-EMIG were voluntarily asked to participate in the online survey. Results of the survey were summarized using descriptive statistics and thematic analysis.Results49 responses (46.7% response rate) were collected and analysed. Participants included 29 (59.2%) male and 20 (40.8%) female medical students. The majority of participants were fourth year students 22 (44.9%). 44 (89.8%) students joined MUST-EMIG to learn how to handle medical emergencies, and expressed a desire of at least 6/10 to learn more about emergency medicine after utilising opportunities provided by MUST-EMIG. Overall, students had a good experience with MUST-EMIG. They reported that our interest group had provided them networking, unique learning, and leadership opportunities. Having an EMIG significantly affects students’ desire to pursue a career in emergency medicine and their perception of the relevance of emergency medicine.ConclusionAn EMIG helps develop interest of medical students in emergency medicine. Students passionate about emergency medicine need to be supported to help them preserve and further develop this passion.
Electronic Medical Record Use and Associated Factors in Diredawa, Eastern Ethiopia. A mixed Method Study
Authors: Tolera Abebe , Oljira Lamessa , Dingeta Tariku , Abaerei Admas Abera , Shore Hirbo
Published: February 2022

Background: Despite rapid growth in the information technology (IT), adoption rate of electronic medical records (EMR) in health care setting is lagging behind in Ethiopia. EMRs have long been considered as essential elements in improving healthcare quality and safety, enhance service performance, reduce adverse events for patients, and support clinical decision support system. However, utilization of EMR among healthcare providers still remains low and there has been little progress toward harnessing the benefits of EMR particularly in developing countries. Objective: This study, therefore, is aimed at exploring EMR use and its determinants among health care providers. Methods: Quantitative cross-sectional study was conducted on 402 health professionals working at public health facilities supplemented with an exploratory qualitative study in Dire Dawa, Ethiopia. Descriptive statistics and logistic regression analysis were used to explore determinant factors of EMR use while qualitative data were thematically analyzed. Results: Overall, about a quarter (26.6%) of health professionals were using electronic medical record. Work experience of 6 years or less (AOR=2.23; 95% CI: [1.15-4.31]), discussion on EMR (AOR=14.47; 95% CI: [5.58-37.57]), presence of EMR manual (AOR=3.10 95%CI: [1.28-7.38]), and positive attitude towards EMR system (AOR=11.15; 95%CI: [4.90-25.36]) and service quality (AOR=8.02; 95% CI: [4.09-15.72]) were independent determinants of EMR use.Conclusion: The analysis carried out indicates that EMR use by health professionals in the study area is very low. Therefore, there is a need to leverage through continuous technical support and commitment to enhance EMR use which has the potential to improve health service performance.
In vitro efficacy of albendazole-loaded β-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto
Authors: Bakhtiar Nayer Mehdizad , Akbarzadeh Abolfazl , Ahmadpour Ehsan , Mahami-Oskouei Mahmoud , Casulli Adriano , Norouzi Roghayeh , Asadi Milad , Ebrahimi Mina , Asadi Nahideh , Oliveira Sonia M. Rodrigues , Pereira Maria de Lourdes , Spotin Adel
Published: February 2022

Background: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus is represented as a public health concern in humans. The therapeutic failure of albendazole (ABZ) against CE depends on its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have been also observed following the long-term use of ABZ in vivo. Methods: We evaluated the apoptotic effects of ABZ-loaded β-cyclodextrin (ABZ-β-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure time, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-β-CD. To assess the treatment efficacy of ABZ-β-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. Results: A significant scolicidal activity of ABZ was observed only at a concentration of 800 μg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 μg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 μg/mL ABZ-β-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that ABZ and ABZ-β-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the ABZ-β-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference against growth and antioxidant properties of PSCs. Conclusions: These data provide new insights into the nanostructured β-CD carriers of ABZ appear as a promising candidate to improve the treatment of CE in vivo models.
A Landscape Assessment of the Activities and Capacities of Evidence to Policy Intermediaries (EPI) in Behavioral Health
Authors: Almquist Lars , Walker Sarah Cusworth , Purtle Jonathan
Published: February 2022

Background:A significant gap exists between the production of research evidence and its use in behavioral health policymaking. Organizations providing consulting and support activities for improving policy represent a promising source for strengthening the infrastructure to address this gap. Understanding the characteristics and activities of these evidence-to-policy intermediary (EPI) organizations can inform the development of capacity-building activities, leading to strengthened evidence-to-policy infrastructure and more widespread evidence-based policymaking.Methods:Online surveys were sent to 51 organizations from English-speaking countries involved in evidence-to-policy activities in behavioral health. The survey was grounded in a rapid evidence review of the academic literature regarding strategies used to influence research use in policymaking. The review identified 17 strategies, which were classified into four activity categories. We administered the surveys via Qualtrics and calculated descriptive statistics, scales, and internal consistency statistics using R.Results:A total of 31 individuals completed surveys from 27 organizations (53% response rate) in four English-speaking countries. EPIs were evenly split between university (49%) and non-university settings (51%). Nearly all EPIs conducted direct program support (mean=4.19/5 [sd=1.25]) and knowledge-building (4.03 [1.17]) activities. However, engagement with traditionally marginalized and nontraditional partners (2.84 [1.39]) and development of evidence reviews using formal critical appraisal methods (2.81 [1.70]) were uncommon.EPIs tend to be specialized, focusing on a group of highly related strategies rather than incorporating multiple evidence-to-policy strategies in their portfolios. Inter-item consistency was moderate to high, with scale α’s ranging from 0.67 to 0.85. Ratings of respondents’ willingness to pay for training in one of three evidence dissemination strategies revealed high interest in program and policy design.Conclusions:Our results suggests that evidence-to-policy strategies are frequently used by existing EPIs; however, organizations tend to specialize rather than engage a breadth of strategies. Further, few organizations reported consistently engaging with non-traditional or community partners. Focusing on building capacity for a network of new and existing EPIs could be a promising strategy for growing the infrastructure needed for evidence-informed behavioral health policymaking.
Carbon Stock And Spatial Dynamics In Natural Forests Of Awi Zone, Amhara Region, Northwestern Ethiopia: Implication For Climate Change Mitigation And Adaptation
Authors: Kassaye Melkamu , Derebe Yonas , Kibrie Wondwosson , Debebe Fekadu , Gedamu Bahiru
Published: February 2022

Background: As a mitigation measure of climate change, the natural forest plays a key role in controlling the carbon cycle and ecosystem stability through sequestrating the carbon dioxide. However, there have been limited scientifically investigation and communication of the potential carbon stock potential of natural forest resources with the global community. Therefore, inventory and estimation of stocks and fluxes of carbon from natural vegetation under different forest communities and different environmental patterns should be done and communicate to the global community for conservation and to get appropriate credit. To do this, 9 forest communities in different agroecology were selected areas of Awi Zone, Northwest Ethiopia. To this end 76 quadrates with 20meter*20meter quadrate size 200meter distance within quadrates and transect lines Diameter, height, and environmental gradient data were collected and analyzed with R Ver.3.1, XLSTAT, and SPSS Ver.25. Result: There was a significant difference (p < 0.029) of above and belowground biomass, carbon stock, carbon dioxide sequestration potential, and soil organic carbon across forests communities, slope, altitude, aspect, and agro-ecologies. ‘Saharakani’ forest has the highest carbon stock as the overall pool. Highland forest communities had a better overall carbon pool. In terms of slop gradient, low slope gradient has recorded the highest allover carbon pool followed by a steep slope and lower slope. In altitude gradient all over carbon pool have in decreasing order with increasing of altitude. South facing had the highest carbon stock as overall pools followed by east-facing and west-facing and the least is north facing. Lowland forests had better Soil organic carbon followed by highland and mid-altitude forests. Carbon stock as an overall pool is especially dynamics within environmental patterns. Conclusion: There is a huge amount of carbon stock in the natural forest in the study area which has a great potential in carbon dioxide sequestration which mitigates the crisis of climate change. However, appropriate credit was not given yet for this natural forest and the resources are continuously declining. Thus, first of all, urgent conservation is required, and then further plan-based sustainable conservation should work should be done for successfully ecologically climate change mitigation.
Encephalitis on An Immunocompromised Patient Following Covid-19 Vaccination. Causal Or Coincidental Correlation?
Authors: Grosi Effrosyni , Tsolaki Anthoula , Saoulidis Iordanis , Liouta Eleni , Savopoulos Christos , Bakaimi Isidora , Spilioti Martha
Published: February 2022

The Covid-19 pandemic has made a major impact worldwide. The vaccines production was a huge biotechnology achievement empowering the defense against this fatal threat. However, as billions of shots have been administered, some safety issues have been raised. We present a case of a 55-year-old patient with a history of CLL(Chronic Lymphocytic Leukemia), who had encephalitis seventeen days post vaccination. Although the benefits outweigh the risk of vaccination at this point, all the rare and serious adverse events should be reported. The significance of such reports is even greater when refer to special patient sub-groups, regarded as immunocompromised.
Developing A Risk Stratification Tool For Predicting Opioid-Related Respiratory Depression After Noncardiac Surgery
Authors: Roy Sounak , Bruehl Stephen , Feng Xiaoke , Shotwell Matthew S. , De Ven Thomas Van , Shaw Andrew D. , Kertai Miklos D.
Published: February 2022

Background: Accurately assessing the probability of significant respiratory depression following opioid administration can potentially enhance perioperative risk assessment and pain management. We developed and validated a risk prediction tool to estimate the probability of significant respiratory depression (indexed by naloxone administration) in patients undergoing noncardiac surgery. Methods: We studied n=63,084 patients (mean age 47.1±18.2 years; 50% male) who underwent emergency or elective noncardiac surgery between January 1st, 2007 and October 30th, 2017 at Vanderbilt University Medical Center. A derivation subsample reflecting two-thirds of available patients (n=42,082) was randomly selected for model development, and associations were identified between predictor variables and naloxone administration occurring within 5 days following surgery. The resulting probability model for predicting naloxone administration was then cross-validated in a separate validation cohort reflecting the remaining one-third of patients (n=21,002).Results: The rate of naloxone administration was identical in the derivation (n = 2,720 [6.5%]) and validation (n = 1,360 [6.5%]) cohorts. The risk prediction model identified female sex (Odds Ratio [OR]: 3.01; 95% confidence interval [CI]: 2.73-3.32), high-risk surgical procedures (OR: 4.16; 95% CI: 3.78-4.58), history of drug abuse (OR: 1.81; 95% CI: 1.52-2.16), and any opioids being administered on a scheduled rather than as-needed basis (OR: 8.31; 95% CI: 7.26-9.51) as risk factors for naloxone administration. Advanced age (OR: 0.40; 95% CI: 0.36-0.43), opioids administered via patient-controlled analgesia pump (OR: 0.55; 95% CI:0.49-0.62), and any scheduled non-opioids (OR: 0.63; 95% CI: 0.58-0.69) were associated with decreased risk of naloxone administration. An overall risk-prediction model incorporating the common clinically-available variables above displayed excellent discriminative ability both the derivation and validation cohorts (c-index = 0.820 and 0.814, respectively).Conclusion: Our cross-validated clinical predictive model accurately estimates the risk of serious opioid-related respiratory depression requiring naloxone administration in postoperative patients. In the precision medicine context, it may prove useful in facilitating selection of opioid-sparing pain management strategies for high-risk surgical patients.
Implementation Strategies Preferred by Primary Care Clinicians to Facilitate Cancer Prevention and Control Activities
Authors: Glasgow Russell , Brtnikova Michaela , Dickinson L. Miriam , Carroll Jennifer K. , Studts Jamie L.
Published: February 2022

Introduction: Key stakeholders need to be involved in the identification of feasible and impactful implementation strategies for evidence-based interventions. While a wide range of implementation strategies has been developed, there is little research on their applicability when addressing different cancer prevention and control (CPC) efforts in primary care.Methods: With an emphasis on rural practices, we conducted a survey of primary care physicians to identify implementation strategies they perceive as most feasible and impactful. The survey included both primary prevention behavior change counseling and cancer screening issues. Analyses contrasted ratings of feasibility and impact across these activities and nine implementation strategies, and among clinicians in different settings with a focus on comparisons between clinicians in rural vs. non-rural settings.Results: We had 326 respondents from a wide range of practice types, representing four different practice-based research networks, 49 states, and including 177 clinicians in rural settings. Ratings of impact were somewhat higher than those for feasibility. Few of the nine implementation strategies were high on both impact and feasibility. Only ‘adapting to my practice’ was rated higher than a 4 (“moderate”) on both impact and feasibility. There were relatively few differences between rural and non-rural clinicians or associated with other clinician or setting characteristics.Conclusions: There is considerable variability in perceived impact and feasibility of implementation strategies for CPC activities among primary care clinicians. It is important to assess both feasibility and impact of implementation strategies as well as their generalizability across settings. Our results suggest that optimal strategies to implement evidence-based CPC activities will likely need to be developed or adapted for primary care settings. Future research is needed to replicate these findings with different settings and interventions, and identify practical, stakeholder informed implementation strategies.
IL-2 and zoledronic acid therapy restores the in vivo anti-leukemic activity of human lymphocytes pre-exposed to simulated microgravity
Authors: Mylabathula Preteesh Leo , Diak Douglass M. , Baker Forrest L. , Niemiro Grace M. , Markofski Melissa M. , Crucian Brian E. , Katsanis Emmanuel , Simpson Richard J.
Published: February 2022

Background: We have previously shown that the anti-tumor activity of human lymphocytes is diminished in vitro after 12-hours pre-exposure to simulated microgravity (SMG). Here we used an immunocompromised mouse model to determine if this loss of function would extend in vivo, and to also test the efficacy of IL-2 and zoledronic acid (ZOL) therapy as a potential countermeasure against SMG-induced immune dysfunction. We adoptively transferred human lymphocytes that were exposed to either SMG or 1G-control into NSG-Tg(Hu-IL 15) mice 1-week after they were injected with a luciferase-tagged human chronic myeloid leukemia (K562) cell line. Tumor growth was monitored 2x weekly with bioluminescence imaging (BLI) for up to 6-weeks. Results: Mice that received lymphocytes exposed to SMG showed greater tumor burden compared to those receiving lymphocytes exposed to 1G (week 6 BLI: 1.8e10 ± 8.07e9 versus 2.22e8 ±1.39e8 photons/second; p<0.0001). Peak BLI was also higher in the SMG group compared to 1G-control (2.34e10 ±1.23e10 versus 3.75e8 ±1.56e8 photons/second; p=0.0062). Exposure to SMG did not affect the ability of human lymphocytes to engraft or evoke xeno-graft-versus-host disease in the mice. Additionally, we injected the mice with IL-2 and zoledronic acid (ZOL) to expand and activate the anti-tumor activity of NK cells and γδ-T cells, respectively. This was found to revive the loss in anti-leukemic function observed in vivo when lymphocytes were pre-exposed to SMG. Conclusion: Microgravity plays a contributory role in loss of tumor control in vivo. Immuno-stimulating agents like ZOL+IL-2 may offer an important countermeasure for immune dysregulation during prolonged spaceflight.
Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy, Risk Factors, and Role of Prophylactic Antibiotics: Data From the US Immunodeficiency Network (USIDNET)
Authors: Syed Maha N. , Kutac Carleigh , Miller Jennifer M , Marsh Rebecca , Rundles Charlotte Cunningham , Fuleihan Ramsay L , Kheradmand Farrah , Hajjar Joud
Published: February 2022

Background Despite immunoglobulin replacement (IgRT) therapy, some patients with Primary Antibody Deficiency (PAD) continue to develop respiratory infections. Recurrent and severe respiratory infections, particularly pneumonia, can lead to significant morbidity and mortality. Therefore, we sought to determine the risk factors of developing pneumonia in PAD patients, already receiving IgRT.MethodsWe evaluated clinical, and laboratory features of PAD patients enrolled in the US Immune Deficiency Network (USIDNET) registry by April 2017. Patients were included if they met the following criteria: 1) PAD diagnosis (common variable immunodeficiency (CVID), Agammaglobulinemia, hypogammaglobinemia, and specific antibody deficiency (SAD). 2) Available data on infections before and after IgRT. Patients were excluded if they were not receiving IgRT, or no pre/post infections data were available. Descriptive and multivariable logistic regression analyses were used to identify factors associated with pneumonia post-IgRT.Results A total of 1286 patients met the inclusion criteria. Following IgRT, 226 patients (17.6%) were reported to have at least one pneumonia episode. Using multivariate logistic regression analysis, we found a statistically significant increased risk of pneumonia in patients with asthma (OR: 1.79, 95% CI [1.20-2.67], p=0.004), bronchiectasis (OR: 2.81, 95% CI [1.64-4.80], p<0.001), and interstitial lung disease (ILD) (OR: 2.90, 95% CI [1.26-6.70], p=0.013). Patients who did not receive prophylactic antibiotics had a much higher risk of pneumonia (OR: 27.65, 95% CI [8.63-88.59]; p<0.001), compared to those who received prophylactic antibiotics. For every 50 unit increase in IgA, the odds of reporting pneumonia post-IgRT decreased significantly (OR: 0.82, 95% CI [0.69-0.97], p=0.018). Patients with X-Linked Agammaglobulinemia had a lower risk of pneumonia than other PAD diagnoses (OR: 0.84; 95% CI [0.75-0.93]; p=0.001). The infectious organism was reported in 39 of 226 patients who reported pneumonia after IgRT. Haemophilus influenzae was the most frequently reported (n=11, 28.21%), followed by Streptococcus Pneumoniae (n=9, 23.08%).ConclusionOur findings suggest a role for prophylactic antibiotics patients with PAD, especially in those with pre-existing lung disease. However, our study is limited by the cross-sectional nature of the USIDNET database and limited longitudinal data. Therefore, prospective studies evaluating the indications of prophylactic antibiotics are warranted.Clinical ImplicationsPatients with primary antibody deficiency and structural lung disease may benefit from prophylactic antibiotics to prevent persisted infections despite IgRT.
Nutritional Benefit of Remnant Gastric Preservation in Patients with Esophageal Cancer Undergoing Radical Esophagectomy and Right Colon Interposition
Authors: Kitadani Junya , Ojima Toshiyasu , Hayata Keiji , Goda Taro , Takeuchi Akihiro , Katsuda Masahiro , Tominaga Shinta , Fukuda Naoki , Nakai Tomoki , Nagano Shotaro , Yamaue Hiroki
Published: February 2022

Background
This retrospective study aimed to investigate the short-term surgical outcomes and nutritional status of right colon interposition in patients with esophageal cancer who could not undergo gastric tube reconstruction.
Methods
64 patients underwent subtotal esophagectomy with reconstruction using right colon interposition for esophageal cancer at Wakayama Medical University Hospital between January 2001 and July 2020.
Results
18 patients had cologastrostomy and 46 patients had colojejunostomy. The median operation time in the cologastorostomy group was significantly shorter than that in the colojejunostomy group (494 minutes vs. 600 minutes; P = 0.0013). And, the median amount of blood loss in the cologastrostomy group was significantly less than that in the colojejunostomy group (209 ml vs. 485 ml; P = 0.037). The perforation of colon graft was observed in 3 patients (7%) and colon graft necrosis was observed in 1 patient (2%) were each observed in the gastrojejunostomy group. Median body weight change in one year after surgery in the cologastrostomy group was significantly less than that of the colojejunostomy group (93.6% vs. 86.8%; P = 0.041). Further, each of median serum total protein level and serum albumin level in one year after surgery in the cologastrostomy group was significantly higher than that of the colojejunostomy group (7.0g/dL vs. 6.5g/dL, P = 0.024, 3.9g/dL vs. 3.6g/dL, P = 0.045).
Conclusions
Subtotal esophagectomy with reconstruction using right colon interposition is a safe and feasible procedure for the patients with esophageal cancer in whom gastric tubes cannot be used. Cologastrostomy with preserving remnant stomach had benefits of the surgical outcomes and the postoperative nutritional status.
A molecular-engineered rotaxane overcomes longstanding biofluid-challenges and enables optical tryptophan detection in human serum
Authors: Krämer Joana , Grimm Laura , Zhong Chunting , Hirtz Michael , Biedermann Frank
Published: February 2022

Despite excelling in simple solvent mixtures, almost all known supramolecular chemosensors cannot be applied in real biofluids due to their adverse interactions with salts, proteins, and other biomolecules. Instead of following the established strategy of searching for alternative synthetic binders with improved affinity and selectivity parameters, we herein report a molecular engineering approach that specifically addresses this bio¬fluid challenge. The developed dual-macrocycle rotaxane is the first supramolecular system that can sense the biomarker tryptophan in biofluids at physiological relevant concentrations, even in protein- and lipid-containing blood serum. Moreover, this chemosensor is used for emission-based high-throughput screening in a microplate format, in label-free enzymatic reaction monitoring, and in chirality sensing through induced circular dichroism. Printed sensor chips with surface-immobilized microarrays of this rotaxane were used for fluorescence microscopy imaging of tryptophan. Our chemosensor achieves a long-awaited applicability in complex biomedia and will foster future applications of supramolecular sensors for molecular diagnostics.
Early effects of ovariectomy on bone microstructure, bone turnover markers and mechanical properties in rats
Authors: Guo Xingman , Yu Xiyue , Yao Qianqian , Qin Jian
Published: February 2022

Background: Fragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of PMOP is very important for elderly women.Methods and materials: Forty 12-week-old female rats were divided into two groups including the ovariectomy group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bodies and femurs were dissected completely for micro-CT scanning, biological modulus detection and histomorphological observation.Results: In OVX group, BV/TV, Conn.D and Tb.N decreased significantly with time (P＜0.05). The elastic modulus of femur in OVX group was lower than that in control group, but there was no significant difference between them (P＞0.05). Over time, the TRAP, BGP, PINP and CTX-I in OVX group increased significantly (P＜0.05). The micrographs of the OVX group showed sparse loss of the trabecular interconnectivity and widening intertrabecular spaces over time. Conclusion: The bone turnover rate of OVX rats in the early stage of estrogen deficiency increased. The bone loss patterns of vertebral body and femur were different, and the changes of biomechanical properties weren’t obvious.
Prognostic biomarker IL17A correlated with immune infiltrates in head and neck cancer
Authors: Yu Meng , Qian XingXing , Li Guang , Cheng Zexing , Lin Zhijie
Published: February 2022

Objective
The underlying functions and mechanisms of the Th17 pathway in Head and neck squamous cell carcinoma (HNSCC) progression and tumor immunology are still unclear. We investigated the correlation between IL17A expression and certain clinical parameters, tumor-infiltrating immune cells (TIICs) in TCGA HNSCC samples.
Methods
HNSCC files from the TCGA database were analyzed to obtain data on immune system infiltrates, gene expression, and related clinical information. R(Version 3.6.3) software, GEPIA and TIMER online analysis tools were used to profile the relationship between the expression of IL17A and the prognosis, clinical stages, survival status and immune cell tumor-infiltrating levels of HNSCC patients. GEPIA and TIMER online analysis tools were used to verify the data.
Results
The expression of IL17A was significantly decreased in tumor tissues from HNSCC. IL17A expression was associated with M, N stage, lymphovascular invasion and patients OS event. GSEA revealed that IL17A was closely related to humoral immune response, T cells response and cytokine signal. TCGA database and TIMER online analysis indicated that the B cells and T cells levels were correlated with IL17A. The correlation between IL17A expression and correlated genes was analyzed.
Conclusion
IL-17A plays a key role in HNSCC. The levels of IL17A are important values for the determination of the occurrence and development of the HNSCC. The IL17A and correlated genes may be potential immunotherapeutic targets for HNSCC.
RETRACTED: Near-Surface Site Characterization of Shimla city, Northwest Himalaya using Combination of Passive and Active Seismic methods
Authors: SHARMA HARSH , Mahajan Ambrish Kumar
Published: February 2022

The authors have requested that this preprint be removed from Research Square.
Heat flux Distribution Model and Transient Temperature Field Analysis in Grinding of Helical Raceway
Authors: Guo Zongfu , Yi Jun , Hu Xiaoping , Wang Jiugen , Zhao Kun
Published: February 2022

To solve the problem of low processing efficiency of screw helical raceway by using high-efficiency grinding technology, this paper carried out theoretical, simulation and experimental analysis on the grinding temperature which mainly affects the selection of high-efficiency grinding process parameters. First, based on the distribution characteristics of the grinding allowance of the screw helical raceway, the analysis shows that the geometry of the grinding contact area is trapezoidal. Then, based on the existing triangular heat flux distribution model of the rectangular contact area, two heat flux distribution models of the triangle and the concave triangle are proposed according to the characteristics of the trapezoidal contact area. Finally, the plane grinding experiment was carried out to correct the simulation parameters, and the modified simulation parameters were used to predict the grinding temperature of the screw raceway, so as to achieve the maximum removal efficiency and avoid burns. The analysis results show that the highest temperature in the grinding area is on the lowest point of the helical raceway, and the temperature and temperature gradient in the grinding area obtained by using the concave triangular heat flux distribution model are the highest. By comparing the process parameters for the onset of grinding burns predicted by simulation and experimentally, the temperature predicted by the concave triangle heat flux distribution model in the trapezoidal contact area is higher than the actual temperature, while the temperature predicted by the triangle heat flux distribution model in the trapezoidal contact area is lower than the actual temperature.