bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Care Resource Nurse Team
Authors: Christopher-Dwyer Katherine , Scanlon Katherine G. , Crimlisk Janet T.
Published: November 2021

The Critical Care Resource Nurse Team (CCRNT) evolved from our traditional Rapid Response Team (RRT). The CCRNT is a unique paradigm created using the conceptual framework of the American Association of Critical Care Nursing Synergy Model for Patient Care. The goal of the CCRNT is to help align nurse competencies with patient needs. This team was seen as a much-needed strong clinical support by nursing leadership as large numbers of inexperienced new graduate registered nurses were hired and senior experienced nurses were leaving the workforce. The CCRNT supports 24/7 RRT, Code Blue, Code Stroke, Emergency Airway Response Team, Early Warning System, Medical Emergency Team, simulation team training, and bedside nurse support and mentoring. Coverage expanded from inpatient medical/surgical areas to all areas of the medical center and included hospital-wide initiatives. The focus for the CCRNT changed to a system-wide nursing and patient safety model to improve practice and intervene in near-miss events. This model improved communication between disciplines, provided critical surveillance of at-risk patients, supported patient safety with a significant decrease in patient mortality, and offered a 24/7 expert critical care nurse resource team for staff.
Maneuvering the Institutional Review Board Process
Authors: Aldridge Michael D.
Published: November 2021

Institutional review boards (IRBs) exist to protect the rights and welfare of research participants. Critical care nurses and researchers may interface with IRBs directly or indirectly. Having an understanding of how the IRB process works will help nurses advocate for patients who may also be research participants and will help researchers facilitate approval of their research studies.
Polidocanol Sclerotherapy in Pyogenic Granulomas
Authors: Khurana Ananta , Mathachan Sinu Rose
Published: November 2021

BACKGROUND

Polidocanol is a safe sclerosing agent with anesthetic properties and minimal skin toxicity.

OBJECTIVE

To evaluate the efficacy, safety, and recurrence rates with polidocanol sclerotherapy in the treatment of pyogenic granulomas (PGs).

METHODS AND METHODS

Thirty-nine patients with PG were injected with polidocanol 1% solution. Repeat injections were given weekly in case of incomplete clinical/dermoscopic resolution, until a maximum of 3 sittings. A higher strength (3%) was used for subsequent sessions in those with a minimal response to 1% solution. A final assessment for relapses was performed at 3, 6, and 12 months.

RESULTS

All 39 patients achieved complete resolution (100% clearance rate), with most (n = 26) lesions resolving after the first sitting. Side effects noted were postprocedure pain (22), erythema (2), superficial ulceration (2), paresthesias (1), prominent edema (4), thrombophlebitis (1), cyanotic discoloration (1), purpuric staining around injection site (4), and mild local pruritus (1). The procedure was well tolerated across the age spectrum (4–63 years) included.

CONCLUSION

We report polidocanol to be a highly effective, safe, and cost-effective sclerosant for treatment of PGs with no recurrences or need for special postprocedure care.
Neonatal outcomes following prophylactic administration of phenylephrine or noradrenaline in women undergoing scheduled caesarean delivery
Authors: Singh Apoorva , Jain Kajal , Goel Nitika , Arora Aashima , Kumar Praveen
Published: November 2021

BACKGROUND

There is limited evidence to support the use of noradrenaline over phenylephrine during elective caesarean section with regards to its impact on foetal acidosis. Concerns regarding a deleterious effect of noradrenaline on foetal blood gas analysis because of its β-mimetic activity cannot currently be ruled out by data from randomised controlled trials.

OBJECTIVE

We hypothesised that noradrenaline would be associated with higher umbilical artery base excess values and less foetal acidosis compared with phenylephrine. This study aimed to observe the effect of prophylactic infusions of phenylephrine or noradrenaline in low-risk elective caesarean delivery on umbilical artery blood gas analysis.

DESIGN

A prospective, randomised, double-blind trial.

SETTING

Labour room operating theatre of tertiary care hospital in Northern India from April 2020 to November 2020.

PATIENTS

Full-term, nonlabouring pregnant women, scheduled for elective caesarean delivery under spinal anaesthesia.

INTERVENTION

Equipotent prophylactic infusions of either phenylephrine 100 μg min−1 or noradrenaline 5 μg min−1 were administered to maintain maternal SBP between 90 and 110% of baseline using a predefined algorithm.

MAIN OUTCOME MEASURE

The primary outcome was umbilical artery base excess in noradrenaline versus the phenylephrine group. The incidence of foetal acidosis defined as umbilical artery base excess less than −6 mmol l−1 was also assessed for noradrenaline versus phenylephrine.

RESULTS

Median [IQR] umbilical artery base excess was significantly higher in the noradrenaline group: −5.4 [−6.6 to −4.03] versus −6.95 [−9.02 to −4.53] in the phenylephrine group (P = 0.014). No significant difference in the incidence of foetal acidosis was observed between noradrenaline and phenylephrine groups: 36 versus 54% (P 0.07); difference 18% (95% CI, −1.4 to 35.6%).

CONCLUSION

Prophylactic noradrenaline 5 μg min−1 infusion resulted in higher base excess values compared with phenylephrine 100 μg min−1 infusion. A comparable incidence of foetal acidosis was observed in women receiving either noradrenaline or phenylephrine. Maternal bradycardia was more pronounced with phenylephrine while targeting blood pressure goals.

CTRI

CTRI/2020/03/023986.
Lip Reshaping with LOVE Approach: A Prospective Analysis Based on Two Hyaluronic Acid Fillers
Authors: Bertossi Dario , Nocini Riccardo , van der Lei Berend , Magistretti Philippe , Gualdi Alessandro , Pirayesh Ali , Marchetti Alberto
Published: November 2021

Background:

Aesthetic improvement of the lips with hyaluronic acid fillers is a popular procedure. A comprehensive, modular, and highly individualizable method has been developed: the Lip Omnicomprehensive Volume Enhancement (LOVE) approach. The present study assessed the safety and effectiveness of LOVE across different patient age groups.

Methods:

This was a prospective, single-center study of women aged 20–70 years seeking nonsurgical lip enhancement or asymmetry correction. Three equally sized groups were formed based on patient age: 20–34, 35–45, and 46 years or older. Individualized treatment plans were developed taking into account patient preferences expressed in a pre-injection questionnaire. Treatment used one or more of the three modules of LOVE: lip shape [vermilion border, Vycross (VYC)-17.5]; volume (vermilion body, VYC-17.5); and hydration (submucosal area, VYC-12). Follow-up lasted 6 months.

Results:

Sixty patients were enrolled (mean age: 41.3 ± 13.3 years; n = 20 per age group), all of whom were White. Most were treated with all three LOVE modules. Mean filler quantities increased with age: 20–34 years, 1.1 ± 0.1 mL; 35–45 years, 1.5 ± 0.1 mL; 46 years or older, 1.6 mL ± 0.2 mL. Mean patient satisfaction at 4 weeks [on a seven-point scale from 0 (extremely dissatisfied) to 6 (extremely satisfied)] was 4.8–4.9 in each age group. Apart from minor and transient edema/bruising, there was only one complication: a case of lumps that resolved with home massage.

Conclusion:

The LOVE approach is safe and effective across a range of ages, with high levels of patient satisfaction.
The prevalence of chronic pain in young adults: a systematic review and meta-analysis
Authors: Murray Caitlin B. , de la Vega Rocío , Murphy Lexa K. , Kashikar-Zuck Susmita , Palermo Tonya M.
Published: November 2021

Previous systematic reviews have summarized the prevalence and impact of chronic pain in “average” pediatric (ie, school-age children) and adult (ie, middle-aged individuals) age groups. To the best of our knowledge, this is the first study to describe the prevalence of chronic pain in the subgroup of individuals who fall in between established boundaries of “childhood” and “adulthood”—known as young adulthood. The goal of this research was to meta-analyze prevalence data on pain in young adults based on available data published between 2008 and 2020. Searches were identified with MEDLINE, Embase, and PsycINFO. We included general population and university-based studies presenting prevalence estimates of chronic pain (pain lasting ≥3 months) in young adults. We identified 43 articles providing prevalence estimates across a combined population of 97,437 young adult respondents (age range: 15-34 years), with studies undertaken in 22 countries. Available data allowed for stratification of prevalence according to pain condition. The overall pooled random-effect prevalence rate of chronic pain in young adults was 11.6%, suggesting that 1 in every 9 young adults experience chronic pain worldwide. Prevalence rates varied considerably according to pain condition. Estimates did not vary according to sex, geographic location, and several study methodological characteristics (ie, population type, sampling area, sampling year, investigation period, and assessment method). Overall, young adult chronic pain is common and should be recognized as a major public health concern. Considering the difficulties young adults face accessing adult health care, greater attention is needed to develop transition programs and evidence-based treatments tailored to the unique needs of this age group.
Accuracy of the Simplified HOSPITAL Score in Predicting COVID-19 Readmissions—Exploring Outcomes from a Hospital-at-Home Program
Authors: Gavin Warren , Rager Joshua , Russ Jason , Subramoney Kavitha , Kara Areeba
Published: November 2021

Goal:

As strategies emerge to off-load hospital systems and prevent readmissions amid the COVID-19 pandemic, pragmatic assessments of readmission risk become increasingly important. The simplified HOSPITAL score is an extensively validated tool that predicts 30-day potentially avoidable readmission (PAR). Scores of 0 to 4 predict a 30-day PAR risk of 6.4%, while scores ≥ 5 predict a 30-day PAR risk of 17.3%. Its role in patients with COVID-19 is unknown. Our goal was to assess the simplified HOSPITAL score’s accuracy in patients with COVID-19 and explore outcomes related to a hospital-at-home program.

Methods:

Patients discharged following an admission for clinically symptomatic COVID-19 from two hospitals belonging to the same healthcare system in the Midwest were included. Those who died, discharged to hospice or an acute care hospital, whose length of stay was < 1 day, or who discharged against medical advice were excluded. The simplified HOSPITAL score was tabulated for included patients to predict their 30-day PAR risk. The Brier score was calculated to compare the observed rates of 30-day readmission with rates predicted by the simplified HOSPITAL score. Prediction models with a Brier score <.25 are considered useful.

Principal Findings:

Among 612 patients, the overall 30-day PAR rate was 10.1%. Most patients (n = 522 [85.3%]) had simplified HOSPITAL scores of 0 to 4, and 41 (7.8%) of these patients were readmitted. Among the 90 patients (14.7%) with scores ≥5, 21 (23.3%) were readmitted. The Brier score was 0.088, indicating very good accuracy between the predicted readmission risk and observed readmissions. In patients with scores 0 to 4, readmissions were highest in those discharged to acute or subacute rehabilitation (10.4% [8/77]), intermediate in those discharged home (8.1% [32/394]), and lowest in those discharged to hospital at home (1.9% [1/51]). However, these differences did not reach statistical significance.

Application to Practice:

The simplified HOSPITAL score was accurate in patients with COVID-19 and can be used to direct resources toward those predicted to be at increased risk for readmission and to assess outcomes from readmission reduction strategies. Hospitals at home may be a promising strategy to decrease readmissions in patients with COVID-19.
Association Between Long Working Hours and Chronic Kidney Disease According to Diabetic Status
Authors: Kim Ki Duk , Jang Suk-Yong
Published: November 2021

Objective:

This study aimed to investigate the relationship between long working hours and chronic kidney disease (CKD) according to diabetic status.

Methods:

Twelve thousand seven hundred three full-time employees without diabetes and 2136 with diabetes were included in this study. Participants were grouped according to working hours: ≤40, 41 to 52, and >52 h/week. Multiple logistic regression was used to evaluate the association between working hours and CKD prevalence.

Results:

Participants with diabetes who worked 41 to 52 h/week showed 1.85 times higher odds of CKD (95% CI 1.15–2.96; P = 0.0112) compared with those who worked ≤40 h/week after adjusting for covariates. An interaction between diabetes and long working hours was observed (P for interaction = 0.0212) in the model.

Conclusion:

Long working hours are associated with CKD in participants with diabetes. An interaction between long working hours and diabetes leading to CKD development may exist.
Physician Assistant Education Community Assumptions About an Entry-level Doctoral Degree
Authors: Brown Darwin , Quincy Brenda , Snyder Jennifer
Published: November 2021

Purpose

This study described the assumptions that PA educators hold regarding the option and/or transition to a doctoral entry-level degree for PA graduates.

Methods

A cross-sectional electronic survey of all members of accredited PA programs was administered. The survey comprised 32 Likert-type statements that measured respondents' level of agreement ranging from strongly disagree to strongly agree and general demographic information. Mean scores are reported for each Likert statement and then compared with analysis of variance and post hoc testing for subgroups of baseline variables.

Results

Responses indicate wide-ranging opinions regarding the adoption of an entry-level doctoral degree for PAs. However, the preponderance of responses appeared more neutral or in opposition to an entry-level doctoral degree. The statement with the strongest level of agreement was that “consideration of the entry-level doctoral degree was really about competing with advanced practice nurses.” Educators who were PAs and those who were physicians differed significantly in their responses for 17 of 32 statements.

Conclusion

Most respondents believed that the master's degree is “enough for clinical practice.” If there is not a deliberate discussion informing the transition to a doctoral entry-level degree, then the change is likely to occur at the individual program level as it did with the transition from a certificate to a bachelor's degree and then to a master's degree. If the PA profession moves to the acceptance of an entry-level doctoral degree, the PA professional organizations should continue to be involved in developing a measured plan forward.
The relationship between brain glucose metabolism and insulin resistance in subjects with normal cognition – a study based on 18F-FDG PET
Authors: Chen Yuqi , Qiu Chun , Yu Wenji , Shao Xiaonan , Zhou Mingge , Wang Yuetao , Shao Xiaoliang
Published: November 2021

Objective

Insulin resistance can increase the risk of cognitive dysfunction and dementia. Our purpose is to use 18F-FDG PET imaging to explore the effect of insulin resistance on brain glucose metabolism in cognitively normal subjects.

Methods

A total of 189 cognitively normal subjects who underwent PET examinations were enrolled. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate the presence of insulin resistance. Multivariate linear regression and generalized additive models were used to analyze the association between HOMA-IR and glucose metabolism in the whole brain and evaluate the effects of various covariates. The SPM12 software was used to evaluate the regional effect of insulin resistance on brain glucose metabolism.

Results

After being fully adjusted for confounding factors, HOMA-IR showed an approximately linear negative correlation with brain glucose metabolism (β = −0.219, T = −3.331, P = 0.021). Compared with normal subjects, insulin-resistant subjects had reduced glucose metabolism in bilateral middle temporal gyrus, bilateral middle frontal gyrus, right precentral gyrus, right inferior frontal gyrus, right cuneiform lobe and bilateral cerebellar regions. In cognitively normal subjects, systemic insulin resistance has a significant effect on brain glucose metabolism.

Conclusions

18F-FDG brain PET imaging could be helpful for the early diagnosis and treatment of changes in brain glucose metabolism caused by insulin resistance.
A 4-Part Strategy to Engage Frontline Nurses in Cultural Humility
Authors: Virkstis Katherine , Whitemarsh Karl , Rewers Lauren , Paiewonsky Allyson
Published: November 2021

Although many clinical leaders use the cultural competency model to help clinicians deliver equitable care, evidence on the model's effectiveness is mixed. In this article, the authors propose that nursing leaders adopt cultural humility as a framework that better positions nurses to build trust, engage patients in their care, and improve health outcomes. This article outlines 4 strategies that leaders can use to actively engage staff in cultural humility and support the cultural transformation required to mitigate the impact of clinician bias in care delivery.
Understanding Inpatient Surgical Nurses' Meaningful Recognition Preferences
Authors: Leger Kierrah , Lajoie Debra , Wood Laura J.
Published: November 2021

Nurse leaders have a responsibility to nurture a work environment that prioritizes meaningful recognition. This quality improvement project explored the perceptions of meaningful recognition of inpatient pediatric surgical nurses. Meaningful recognition provides a chance to honor all voices, particularly those that have not been previously heard. To be heard is to be honored and to be recognized is to be valued.
Introducing the 2023 Magnet Application Manual®
Authors: Lal M. Maureen
Published: November 2021

In November, the American Nurses Credentialing Center (ANCC) released its revised 2023 Magnet Application Manual®
, the 13th manual in the program's 31-year history. This month's “Magnet Perspectives” takes a deep dive into the new edition of the manual, examining the rigorous, multistep review process, the modernized standards, and the coalition of experts that contributed insights to inform the latest edition. Each edition raises the bar to promote the highest levels of nursing excellence, and the 2023 manual is no exception. Learn how this forward-looking edition addresses emerging challenges and changes to reflect what is happening in healthcare today.
Adherence to Best Practice Advice for Diagnosis of Pulmonary Embolism
Authors: Prentice Donna , Wipke-Tevis Deidre D.
Published: November 2021

Purpose

This study evaluated clinician adherence to the American College of Physicians Best Practice Advice for diagnosis of pulmonary embolism.

Design

A prospective, single-center, descriptive design was utilized.

Methods

A heterogeneous sample of 111 hemodynamically stable adult inpatients with a computed tomography pulmonary angiogram ordered was consented. Electronic medical records were reviewed for demographic and clinical variables to determine adherence. The 6 individual best practice statements and the overall adherence were evaluated by taking the sum of “yes” answers divided by the sample size.

Results

Overall adherence was 0%. Partial adherence was observed with clinician-recorded clinical decisions rules and obtaining d-dimer (3.6% [4/111] and 10.2% [9/88], respectively) of low/intermediate probability scorers. Age adjustment of d-dimer was not recorded. Computed tomography pulmonary angiogram was the first diagnostic test in 89.7% (79/88) in low/intermediate probability patients.

Conclusion

In hemodynamically stable, hospitalized adults, adherence to best practice guidelines for diagnosis of pulmonary embolism was minimal. Clinical utility of the guidelines in hospitalized adults needs further evaluation. Systems problems (eg, lack of standardized orders, age-adjusted d-dimer values, information technology support) likely contributed to poor guideline adherence.
Mutational Alterations of DNA Methylation-related Genes CTCF, ZFP57, and ATF7IP Genes in Colon Cancers
Authors: Moon Seong Won , Mo Ha Yoon , Choi Eun Ji , Yoo Nam Jin , Lee Sug Hyung
Published: November 2021

Deregulations of DNA-methylation-related genes are common in cancers, but frameshift mutation status in colon cancer (CC) is unknown. Our study aims to assess whether CTCF, ZFP57, and ATF7IP genes in this category are mutated in CC. CTCF, ZFP57, and ATF7IP genes have repeat coding sequences, which are frequently deleted or duplicated in CC, harboring the phenotype of unstable or high microsatellite instability (MSI-H). We studied 140 CCs [95 MSI-H CCs and 45 stable MSI (MSS) CCs], and found 7 CCs with MSI-H (6/95: 6.3%) harbored frameshift mutations within the repeats, whereas those with MSS did not. Of note, the CTCF frameshift mutations showed the regional difference in the 2 (12.5%) of 16 MSI-H CCs, indicating there was intratumoral heterogeneity. In the immunohistochemistry for ATF7IP, the MSI-H CC showed low intensity compared to MSS CC. Together, CTCF, ZFP57, and ATF7IP genes, despite the low incidence of the mutations, are altered in several ways (mutation, expression, and intratumoral heterogeneity) and could contribute to MSI-H CC development.
Saving the ground beneath our feet: Establishing priorities and criteria for governing soil use and protection
Authors: Peake Lewis , Robb Cairo
Published: November 2021

The continual loss and impairment of soil ecosystem services (SES) across the globe calls for a fundamental reconsideration of soil governance mechanisms. This critical synthesis charts the history and evolution of national and international soil law and seeks to unravel certain challenges that have contributed to this failure in governance. It describes and categorizes law and policy responses to different soil threats, and identifies a worrying widespread absence of legislation for oversight and protection of agricultural soils from urbanization, as well as a lack of clear legal mechanisms to determine national priorities for soil protection. A reduction in the world's prime farmland threatens SES, including food security, carbon storage and biodiversity. Falling between the stalls of agricultural and environmental law, the fate of farmland is often left to planners who do not see themselves as responsible for soils. Consequently, legal instruments with the greatest power to affect soil, sometimes irreversibly, are often framed and worded with little or no reference to the soil. Nevertheless, emerging conceptual frameworks might offer positive outcomes. The authors advocate robust holistic policies of soil governance and land use planning that place SES and natural capital at the heart of decision making.
Model-based representational similarity analysis of blood-oxygen-level-dependent fMRI captures threat learning in social interactions
Authors: Undeger Irem , Visser Renée M. , Becker Nina , de Boer Lieke , Golkar Armita , Olsson Andreas
Published: November 2021

Past research has shown that attributions of intentions to other's actions determine how we experience these actions and their consequences. Yet, it is unknown how such attributions affect our learning and memory. Addressing this question, we combined neuroimaging with an interactive threat learning paradigm in which two interaction partners (confederates) made choices that had either threatening (shock) or safe (no shock) consequences for the participants. Importantly, participants were led to believe that one partner intentionally caused the delivery of shock, whereas the other did not (i.e. unintentional partner). Following intentional versus unintentional shocks, participants reported an inflated number of shocks and a greater increase in anger and vengeance. We applied a model-based representational similarity analysis to blood-oxygen-level-dependent (BOLD)-MRI patterns during learning. Surprisingly, we did not find any effects of intentionality. The threat value of actions, however, was represented as a trial-by-trial increase in representational similarity in the insula and the inferior frontal gyrus. Our findings illustrate how neural pattern formation can be used to study a complex interaction.
Rainwater-driven microbial fuel cells for power generation in remote areas
Authors: Amen Mohamed Taha , Yasin Ahmed S. , Hegazy Mohamed I. , Jamal Mohammad Abu Hena Mostafa , Hong Seong-Tshool , Barakat Nasser A. M.
Published: November 2021

The possibility of using rainwater as a sustainable anolyte in an air-cathode microbial fuel cell (MFC) is investigated in this study. The results indicate that the proposed MFC can work within a wide temperature range (from 0 to 30°C) and under aerobic or anaerobic conditions. However, the rainwater season has a distinct impact. Under anaerobic conditions, the summer rainwater achieves a promised open circuit potential (OCP) of 553 ± 2 mV without addition of nutrients at the ambient temperature, while addition of nutrients leads to an increase in the cell voltage to 763 ± 3 and 588 ± 2 mV at 30°C and ambient temperature, respectively. The maximum OCP for the winter rainwater (492 ± 1.5 mV) is obtained when the reactor is exposed to the air (aerobic conditions) at ambient temperature. Furthermore, the winter rainwater MFC generates a maximum power output of 7 ± 0.1 mWm−2at a corresponding current density value of 44 ± 0.7 mAm−2at 30°C. While, at the ambient temperature, the maximum output power is obtained with the summer rainwater (7.2 ± 0.1 mWm−2at 26 ± 0.5 mAm−2). Moreover, investigation of the bacterial diversity indicates thatLactobacillusspp. is the dominant electroactive genus in the summer rainwater, while in the winter rainwater,Staphylococcusspp. is the main electroactive bacteria. The cyclic voltammetry analysis confirms that the electrons are delivered directly from the bacterial biofilm to the anode surface and without mediators. Overall, this study opens a new avenue for using a novel sustainable type of MFC derived from rainwater.
Does it pay to imitate? No evidence for social gains from lexical imitation
Authors: Lelonkiewicz Jarosław R. , Pickering Martin J. , Branigan Holly P.
Published: November 2021

According to an influential hypothesis, people imitate motor movements to foster social interactions. Could imitation of language serve a similar function? We investigated this question in two pre-registered experiments. In Experiment 1, participants were asked to alternate naming pictures and matching pictures to a name provided by a partner. Crucially, and unknown to participants, the partner was in fact a computer program which in one group produced the same names as previously used by the participant, and in the other group consistently produced different names. We found no difference in how the two groups evaluated the partner or the interaction and no difference in their willingness to cooperate with the partner. In Experiment 2, we made the task more similar to natural interactions by adding a stage in which a participant and the partner introduced themselves to each other and included a measure of the participant's autistic traits. Once again, we found no effects of being imitated. We discuss how these null results may inform imitation research.
Molecular characterization of Vibrio cholerae O1 isolates obtained from outbreaks in the Philippines, 2015–2016
Authors: Bugayong Mark Philip , Izumiya Hidemasa , Bilar Josie M. , Morita Masatomo , Arakawa Eiji , Saito-Obata Mariko , Oshitani Hitoshi , Ohnishi Makoto
Published: November 2021

Introduction. The Philippines, comprising three island groups, namely, Luzon, Visayas and Mindanao, experienced an increase in cholera outbreaks in 2016. Previous studies have shown that Vibrio cholerae isolates obtained from the Philippines are novel hybrid El Tor strains that have evolved in the country and are clearly distinct from those found in Mozambique and Cameroon.

Gap statement. The characterization of the strains isolated from outbreaks has been limited to phenotypic characteristics, such as biochemical and serological characteristics, in most previous studies.

Aim. We performed multilocus variable-number tandem repeat (VNTR) analysis (MLVA) for V. cholerae isolates obtained from 2015 to 2016 to further characterize and understand the emergence and dissemination of the strains in the Philippines.

Methodology. A total of 139 V. cholerae O1 Ogawa biotype El Tor isolates were obtained from the Philippines during diarrhoeal outbreaks in 18 provinces between 2015 and 2016. VNTR data were analysed to classify the MLVA profiles where the large-chromosome types (LCTs) were applied for grouping.

Results. We identified 50 MLVA types among 139 isolates originating from 18 provinces, and 14 LCTs. The distribution of the LCTs was variable, and a few were located in specific areas or even in specific provinces. Based on eBURST analysis, 99 isolates with 7 LCTs and 32 MLVA types belonged to 1 group, suggesting that they were related to each other. LCT A was predominant (n=67) and was isolated from Luzon and Visayas. LCT A had 14 MLVA types; however, it mostly emerged during a single quarter of a year. Eight clusters were identified, each of which involved specific MLVA type(s). The largest cluster involved 23 isolates showing 3 MLVA types, 21 of which were MLVA type A-14 isolated from Negros Occidental during quarter 4 of 2016. Comparative analysis showed that almost all isolates from the Philippines were distinct from those in other countries.

Conclusions. The genotypic relationship of the V. cholerae isolates obtained during outbreaks in the Philippines was studied, and their emergence and dissemination were elucidated. MLVA revealed the short-term dynamics of V. cholerae genotypes in the Philippines.
Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein
Authors: Jiang Sheng , Wu Shuting , Zhao Gan , He Yue , Guo Xinrong , Zhang Zhiyu , Hou Jiawang , Ding Yuan , Cheng Alex , Wang Bin
Published: November 2021

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants including the most recent Omicron and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.
Impaired astrocytic Ca2+ signalling in awake Alzheimer’s disease transgenic mice
Authors: Åbjørsbråten Knut Sindre , Syverstad Skaaraas Gry H. E. , Cunen Céline , Bjørnstad Daniel M. , Gullestad Binder Kristin M. , Jensen Vidar , Nilsson Lars N.G. , Rao Shreyas B. , Tang Wannan , Hermansen Gudmund Horn , Nagelhus Erlend A. , Ottersen Ole Petter , Torp Reidun , Enger Rune
Published: November 2021

Increased astrocytic Ca2+ signaling related to amyloid plaques has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signalling in such mice without the confounding effects of anesthesia. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signalling in 15-months old plaque-bearing mice. This points to a potential decoupling of neuromodulatory activation and astrocytic Ca2+ activity, which may account for some of the cognitive dysfunctions observed in Alzheimer’s disease.
Serological responses to COVID-19 booster vaccine in England
Authors: Ireland Georgina , Whitaker Heather , Ladhani Shamez N , Baawuah Frances , Subbarao Vani , Linley Ezra , Warrener Lenesha , O’Brien Michelle , Whillock Corinne , Moss Paul , Ramsay Mary E , Amirthalingam Gayatri , Brown Kevin E
Published: November 2021

Introduction

There are limited data on immune responses after COVID-19 vaccine boosters in individuals receiving primary immunisation with BNT162b2 (Pfizer-BioNTech) or AZD1222 (AstraZeneca).

Methods

A prospective, cohort study to assess SARS-CoV-2 antibody responses before and after booster vaccination with BNT162b2 in adults receiving either (i) two BNT162b2 doses <30 days apart (BNT162b2-control), (ii) two BNT162b2 doses ≥30 days apart (BNT162b2-extended) or (iii) two AZD1222 doses ≥30 days apart (AZD1222-extended) in London, England. SARS-CoV-2 spike protein antibody geometric mean titres (GMTs) before and 2-4 weeks after booster were compared.

Results

Of 750 participants, 626 provided serum samples for up to 38 weeks after their second vaccine dose. Antibody GMTs peaked at 2-4 weeks after the second dose, before declining by 68% at 36-38 weeks after dose 2 for BNT162b2-control participants, 85% at 24-29 weeks for BNT162b2-extended participants and 78% at 24-29 weeks for AZD1222-extended participants. Antibody GMTs was highest in BNT162b2-extended participants (942 [95%CI, 797-1113]) than AZD1222-extended (183 [124-268]) participants at 24-29 weeks or BNT162b2-control participants at 36-38 weeks (208; 95%CI, 150-289). At 2-4 weeks after booster, GMTs were significantly higher than after primary vaccination in all three groups: 18,104 (95%CI, 13,911-23,560; n=47) in BNT162b2-control (76.3-fold), 13,980 (11,902-16,421; n=118) in BNT162b2-extended (15.9-fold) and 10,799 (8,510-13,704; n=43) in AZD1222-extended (57.2-fold) participants. BNT162b2-control participants (median:262 days) had a longer interval between primary and booster doses than BNT162b2-extended or AZD1222-extended (both median:186 days) participants.

Conclusions

We observed rapid serological responses to boosting with BNT162b2, irrespective of vaccine type or schedule used for primary immunisation, with higher post-booster responses with longer interval between primary immunisation and boosting. Boosters will not only provide additional protection for those at highest risk of severe COVID-19 but also prevent infection and, therefore, interrupt transmission, thereby reducing infections rates in the population. Ongoing surveillance will be important for monitoring the duration of protection after the booster.
Germany’s low SARS-CoV-2 seroprevalence confirms effective containment in 2020: Results of the nationwide RKI-SOEP study
Authors: Neuhauser Hannelore , Rosario Angelika Schaffrath , Butschalowsky Hans , Haller Sebastian , Hoebel Jens , Michel Janine , Nitsche Andreas , Poethko-Müller Christina , Prütz Franziska , Schlaud Martin , Steinhauer Hans W. , Wilking Hendrik , Wieler Lothar H. , Schaade Lars , Liebig Stefan , Gößwald Antje , Grabka Markus M. , Zinn Sabine , Ziese Thomas
Published: November 2021

Pre-vaccine SARS-CoV-2 seroprevalence data from Germany are scarce outside hotspots, and socioeconomic disparities remained largely unexplored. The nationwide RKI-SOEP study with 15,122 adult participants investigated seroprevalence and testing in a supplementary wave of the Socio-Economic-Panel conducted predominantly in October-November 2020. Self-collected oral-nasal swabs were PCR-positive in 0.4% and Euroimmun anti-SARS-CoV-2-S1-IgG ELISA from dry capillary blood in 1.3% (95% CI 0.9-1.7%, population-weighted, corrected for sensitivity=0.811, specificity=0.997). Seroprevalence was 1.7% (95% CI 1.2-2.3%) when additionally adjusting for antibody decay. Overall infection prevalence including self-reports was 2.1%. We estimate 45% (95% CI 21-60%) undetected cases and analyses suggest lower detection in socioeconomically deprived districts. Prior SARS-CoV-2 testing was reported by 18% from the lower educational group compared to 25% and 26% from the medium and high educational group (p<0.0001). Symptom-triggered test frequency was similar across educational groups. However, routine testing was more common in low-educated adults, whereas travel-related testing and testing after contact with an infected person was more common in highly educated groups. In conclusion, pre-vaccine SARS-CoV-2-seroprevalence in Germany was very low. Notified cases appear to capture more than half of infections but may underestimate infections in lower socioeconomic groups. These data confirm the successful containment strategy of Germany until winter 2020.
Association Between a 22-feature Genomic Classifier and Biopsy Gleason Upgrade During Active Surveillance for Prostate Cancer
Authors: Press Benjamin H , Jones Tashzna , Olawoyin Olamide , Lokeshwar Soum D , Rahman Syed N , Khajir Ghazal , Lin Daniel W , Cooperberg Matthew R , Loeb Stacy , Darst Burcu F , Zheng Yingye , Chen Ronald C , Witte John S , Seibert Tyler M , Catalona William J , Leapman Michael S , Sprenkle Preston C
Published: November 2021

Background:
Although the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing risks of biopsy reclassification among patients on active surveillance, a key event that often triggers treatment.
Objective:
To evaluate the association between Decipher genomic classifier and biopsy Gleason upgrade among patients on active surveillance.
Design, Setting, and Participants:
Retrospective cohort study among patients with low- and favorable-intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of clinical care.
Outcomes measures and statistical analysis:
Any increase in biopsy Gleason grade group (GG). We evaluated the association between Decipher score using univariable and multivariable logistic regression. We compared area under the receiver operating characteristic curve (AUC) of models comprised of baseline clinical variables with or without Decipher score.
Results and limitations:
We identified 133 patients of median age 67.7 years and median PSA 5.6 ng/mL. At enrollment 75.9% were GG1 and 24.1 GG2. Forty-three patients experienced biopsy upgrade. On multivariable logistic regression, Decipher score was significantly associated with biopsy upgrade (OR 1.37 per 0.10 unit increase, 95% CI 1.05-1.79 p=0.02). Decipher score was associated with upgrade among patients with biopsy Grade group 1, but not Grade Group 2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51-0.74) was improved with the integration of Decipher score (AUC 0.69, 95% CI 0.58-0.80).
Conclusions:
The Decipher genomic classifier was associated with short-term biopsy Gleason upgrading among patients on active surveillance.
Patient summary:
The results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance.
Cocaine exacerbates neurological impairments and neuropathologies in the iTat model of HIV-associated neurocognitive disorder through genome-wide alterations of DNA methylation and gene expression
Authors: Zhao Xiaojie , Zhang Fan , Kandel Suresh R. , Brau Frédéric , He Johnny J.
Published: November 2021

HIV infection of the central nervous system causes HIV-associated neurocognitive disease (HAND) in up to 50% HIV-infected individuals. Cocaine use is prevalent in the HIV-infected population and has been shown to facilitate the HAND progression. However, the cellular and molecular mechanism of the cocaine-facilitated HAND progression remains largely unknown. In this study, we took advantage of the doxycycline inducible and brain-specific HIV Tat transgenic mouse model (iTat) of HAND and characterized effects of chronic cocaine exposure and long- term Tat expression on HAND-associated neurology and neuropathology. We found that cocaine exposure worsened the learning and memory of iTat mice, coupled with dendritic spine swelling, increased synaptophysin expression, and diminished microglia and astrocyte activation. We then employed the single-base resolution whole genome bisulfate sequencing and RNA sequencing and identified 14,838 hypermethylated CpG-related differentially methylated regions (DMR) and 15,800 hypomethylated CpG-related DMR that were linked to 52 down- and 127 up-regulated genes by cocaine and Tat. We further uncovered these genes to be mostly enriched at neuronal function- and cell morphology- and synapse formation-relatedECM-receptor interactionpathway, and to be linked to behavioral and pathological changes altered by cocaine and Tat. Eight mostly affected genes included four in microgliaIft172,Eif2ak4,Pik3c2a,andPhf8, two in astrocytesGarem1andAdgrb3, and two in neuronsDcun1d4andAdgrb3. These findings demonstrated for the first time that cocaine and Tat interactively contributed to HAND neurology and neuropathology through genome-wide changes of DNA methylation and gene expression and suggest that targeting epigenetic changes serves as a potentially new therapeutic strategy to treat cocaine use disorder in people living with HAND.
Genomic variation across a clinical Cryptococcus population linked to disease outcome
Authors: Sephton-Clark Poppy , Tenor Jennifer L. , Toffaletti Dena L. , Meyers Nancy , Giamberardino Charles , Molloy Síle F. , Palmucci Julia R. , Chan Adrienne , Chikaonda Tarsizio , Heyderman Robert , Hosseinipour Mina , Kalata Newton , Kanyama Cecilia , Kukacha Christopher , Lupiya Duncan , Mwandumba Henry C. , Harrison Thomas , Bicanic Tihana , Perfect John R. , Cuomo Christina A.
Published: November 2021

Cryptococcus neoformans is the causative agent of cryptococcosis, a disease with poor patient outcomes, accounting for approximately 180,000 deaths each year. Patient outcomes may be impacted by the underlying genetics of the infecting isolate; however, our current understanding of how genetic diversity contributes to clinical outcomes is limited. Here, we leverage clinical, in vitro growth and genomic data for 284 C. neoformans isolates to identify clinically relevant pathogen variants within a population of clinical isolates from patients with HIV-associated cryptococcosis in Malawi. Through a genome-wide association study (GWAS) approach, we identify variants associated with fungal burden and growth rate. We also find both small and large-scale variation, including aneuploidy, associated with alternate growth phenotypes, which may impact the course of infection. Genes impacted by these variants are involved in transcriptional regulation, signal transduction, glycosylation, sugar transport, and glycolysis. We show that growth within the CNS is reliant upon glycolysis in an animal model, and likely impacts patient mortality, as CNS yeast burden likely modulates patient outcome. Additionally, we find genes with roles in sugar transport are enriched in regions under selection in specific lineages of this clinical population. Further, we demonstrate that genomic variants in two genes identified by GWAS impact virulence in animal models. Our approach identifies links between genetic variation in C. neoformans and clinically relevant phenotypes and animal model pathogenesis; shedding light on specific survival mechanisms within the CNS and identifying pathways involved in yeast persistence.

Importance

Infection outcomes for cryptococcosis, most commonly caused by C. neoformans, are influenced by host immune responses, as well as host and pathogen genetics. Infecting yeast isolates are genetically diverse; however, we lack a deep understanding of how this diversity impacts patient outcomes. To better understand both clinical isolate diversity and how diversity contributes to infection outcome, we utilize a large collection of clinical C. neoformans samples, isolated from patients enrolled in a clinical trial across 3 hospitals in Malawi. By combining whole-genome sequence data, clinical data, and in vitro growth data, we utilize genome-wide association approaches to examine the genetic basis of virulence. Genes with significant associations display virulence attributes in both murine and rabbit models, demonstrating that our approach can identify potential links between genetic variants and patho-biologically significant phenotypes.
Is It Really Musculoskeletal Pain? Differential diagnosis and screening for referral in paediatric musculoskeletal disorders: a scoping review protocol
Authors: D’Aversa A , Bonetti F , Gallotti M , Maselli F
Published: November 2021

Introduction

Musculoskeletal disorders are common in children and adolescents. They could have a broad spectrum of causes, which the most are self-limiting and usually do not need a referral to specialistic care. It is mandatory for the healthcare professionals working primary care settings to be able to understand when to perform a “wait and see” approach or when further investigations are needed. This study aims to identify signs and symptoms reliable to serious or life-threatening conditions that could be detected during the screening process and the physical examination of children and adolescent with common musculoskeletal disorders by a healthcare professional in direct access clinical setting.

Materials and Methods

The scoping review (ScR) will be performed following the six-stage methodology suggested by Arksey and O’Malley and the extensions to the original framework that are recommended by the Joanna Briggs Institute. Fourteen electronic databases will be investigated since their inception. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist will be used to meet the required standards of quality and reproducibility. Review tools will be used for the quality assessment of the included studies. This protocol received input from all authors who have expertise in research methodology and paediatric and musculoskeletal disorders.

Ethics and Dissemination

The results of this ScR will be relevant given that screening for referral in paediatric musculoskeletal disorders has not been addressed in the literature properly yet. Dissemination will include submission to peer-reviewed journal. Ethical approval is not required for scoping reviews.

PROTOCOL INFORMATION

Anticipated or actual start date: January 2021

Anticipated completion date: December 2021