bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Antibiotic De-escalation by Spectrum Score in Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study
Authors: Ilges Dan , Ritchie David J , Krekel Tamara , Neuner Elizabeth A , Hampton Nicholas , Kollef Marin H , Micek Scott
Published: November 2021

Background

Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.

Methods

This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). The primary outcome was composite treatment failure, defined as all-cause mortality or readmission for pneumonia within 30 days of diagnosis.

Results

Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs 1026 NDE). Groups were well matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs 50.6%, P = .011). There was no difference in composite treatment failure (35.0% DE vs 33.8% NDE, P = .604). De-escalation was not associated with treatment failure on multivariable Cox regression analysis (hazard ratio, 1.13; 95% confidence interval, 0.96–1.33). Patients receiving DE had fewer antibiotic days (median 9 vs 11, P < .0001), episodes of Clostridioides difficile infection (2.2% vs 3.8%, P = .046), and hospital days (median 20 vs 22 days, P = .006).

Conclusions

De-escalation and NDE resulted in similar rates of 30-day treatment failure; however, DE was associated with fewer antibiotic days, episodes of C difficile infection, and days of hospitalization.
Coronavirus Disease 2019–Associated Invasive Fungal Infection
Authors: Baddley John W , Thompson George R , Chen Sharon C -A , White P Lewis , Johnson Melissa D , Nguyen M Hong , Schwartz Ilan S , Spec Andrej , Ostrosky-Zeichner Luis , Jackson Brendan R , Patterson Thomas F , Pappas Peter G
Published: November 2021

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19–associated fungal infections.
Trends and Intensity of Rhinovirus Invasions in Kilifi, Coastal Kenya, Over a 12-Year Period, 2007–2018
Authors: Mwita Morobe John , Kamau Everlyn , Murunga Nickson , Gatua Winfred , Luka Martha M , Lewa Clement , Cheruiyot Robinson , Mutunga Martin , Odundo Calleb , James Nokes D , Agoti Charles N
Published: November 2021

Background

Rhinoviruses (RVs) are ubiquitous pathogens and the principal etiological agents of common cold. Despite the high frequency of RV infections, data describing their long-term epidemiological patterns in a defined population remain limited.

Methods

Here, we analyzed 1070 VP4/VP2 genomic region sequences sampled at Kilifi County Hospital on the Kenya coast. The samples were collected between 2007 and 2018 from hospitalized pediatric patients (<60 months of age) with acute respiratory illness.

Results

Of 7231 children enrolled, RV was detected in 1497 (20.7%) and VP4/VP2 sequences were recovered from 1070 samples (71.5%). A total of 144 different RV types were identified (67 Rhinovirus A, 18 Rhinovirus B, and 59 Rhinovirus C) and at any month, several types co-circulated with alternating predominance. Within types, multiple genetically divergent variants were observed. Ongoing RV infections through time appeared to be a combination of (1) persistent types (observed up to 7 consecutive months), (2) reintroduced genetically distinct variants, and (3) new invasions (average of 8 new types annually).

Conclusions

Sustained RV presence in the Kilifi community is mainly due to frequent invasion by new types and variants rather than continuous transmission of locally established types/variants.
Evolving a New Religious Freedom Jurisprudence: A Step Towards Ensuring Equality for Women
Authors: Jawed Maria , Jadhav Dhanaji Mukundrao
Published: November 2021

India is a country of religious pluralism, and cultural diversity wherein religion is one of the important social institutions. Freedom of religion in India is guaranteed as a fundamental right which comprises ‘freedom to freely profess, practice and propagate religion’ within the Constitutional boundary. The Indian constitution fosters equality to all and has a broader interpretative connotation. Often, the judiciary is posed with the delicate task of settling the sensitive disputes relating to religion. The court's intervention into such practices may lead to a conflict of existing values backed by the religion or society with newly introduced values by the court. Recently, the Supreme Court in the Sabarimala Temple Entry case declared the practice of prohibiting women in their menstruating age from entering the temples as unconstitutional. The article substantiates that the case paves the way for ensuring equality for women in every sphere, including religion. It critically appraises the existing jurisprudence of religious freedom and argues the need to establish a much coherent jurisprudence based on constitutional principles. The article correlates moral, social, and religious intricacies in determining the constitutional validity of religious practices and tries to substantiate it based on developing jurisprudence of constitutional morality.
Galaxy morphologies revealed with Subaru HSC and super-resolution techniques. I. Major merger fractions ofLUV ∼ 3–15 L*UV dropout galaxies atz∼ 4–7
Authors: Shibuya Takatoshi , Miura Noriaki , Iwadate Kenji , Fujimoto Seiji , Harikane Yuichi , Toba Yoshiki , Umayahara Takuya , Ito Yohito
Published: November 2021

We perform a super-resolution analysis of the Subaru Hyper Suprime-Cam (HSC) images to estimate the major merger fractions of z ∼ 4–7 dropout galaxies at the bright end of galaxy UV luminosity functions (LFs). Our super-resolution technique improves the spatial resolution of the ground-based HSC images, from ∼1″ to $\lesssim \!\!{0{^{\prime \prime }_{.}}1}$, which is comparable to that of the Hubble Space Telescope, allowing us to identify z ∼ 4–7 bright major mergers at a high completeness value of $\gtrsim \!\!90\%$. We apply the super-resolution technique to 6412, 16, 94, and 13 very bright dropout galaxies at z ∼ 4, 5, 6, and 7, respectively, in a UV luminosity range of LUV ∼ 3–$15\, L_{\rm UV}^*$ corresponding to −24 ≲ MUV ≲ −22. The major merger fractions are estimated to be $f_{\rm merger}\sim 10\%$–$20\%$ at z ∼ 4 and $\sim 50\%$–$70\%$ at z ∼ 5–7, which shows no fmerger difference compared to those of a control faint galaxy sample. Based on the fmerger estimates, we verify contributions of source blending effects and major mergers to the bright-end of double power-law (DPL) shape of z ∼ 4–7 galaxy UV LFs. While these two effects partly explain the DPL shape at LUV ∼ 3–$10\, L_{\rm UV}^*$, the DPL shape cannot be explained at the very bright end of $L_{\rm UV}\gtrsim 10\, L_{\rm UV}^*$, even after the AGN contribution is subtracted. The results support scenarios in which other additional mechanisms such as insignificant mass quenching and low dust obscuration contribute to the DPL shape of galaxy UV LFs.
Protection of photosystem I during sudden light stress depends on ferredoxin:NADP(H) reductase abundance and interactions
Authors: Rodriguez-Heredia Melvin , Saccon Francesco , Wilson Sam , Finazzi Giovanni , Ruban Alexander V , Hanke Guy T
Published: November 2021

Plant tolerance to high light and oxidative stress is increased by overexpression of the photosynthetic enzyme Ferredoxin:NADP(H) reductase (FNR), but the specific mechanism of FNR-mediated protection remains enigmatic. It has also been reported that the localization of this enzyme within the chloroplast is related to its role in stress tolerance. Here, we dissected the impact of FNR content and location on photoinactivation of photosystem I (PSI) and photosystem II (PSII) during high light stress of Arabidopsis (Arabidopsis thaliana). The reaction center of PSII is efficiently turned over during light stress, while damage to PSI takes much longer to repair. Our results indicate a PSI sepcific effect, where efficient oxidation of the PSI primary donor (P700) upon transition from darkness to light, depends on FNR recruitment to the thylakoid membrane tether proteins: thylakoid rhodanase-like protein (TROL) and translocon at the inner envelope of chloroplasts 62 (Tic62). When these interactions were disrupted, PSI photoinactivation occurred. In contrast, there was a moderate delay in the onset of PSII damage. Based on measurements of ΔpH formation and cyclic electron flow, we propose that FNR location influences the speed at which photosynthetic control is induced, resulting in specific impact on PSI damage. Membrane tethering of FNR therefore plays a role in alleviating high light stress, by regulating electron distribution during short-term responses to light.
A Scoping Review of the Diurnal Variation in the Intensity of Neuropathic Pain
Authors: Hu Sally , Gilron Ian , Singh Mandeep , Bhatia Anuj
Published: November 2021

Background

Recent studies have suggested that neuropathic pain exhibits a daily diurnal pattern, with peak levels usually occurring in the late afternoon to evening and the trough in the morning hours, although literature on this topic has been sparse. This scoping review examines current evidence on the chronobiology of neuropathic pain both in animal models and in humans with neuropathic pain.

Methods

A literature search was conducted in major medical databases for relevant articles on the chronobiology of neuropathic pain both in animal models and in humans with neuropathic pain. Data extracted included details of specific animal models or specific neuropathic pain conditions in humans, methods and timing of assessing pain severity, and specific findings of diurnal variation in pain intensity or its surrogate markers.

Results

Thirteen animal and eight human studies published between 1976 and 2020 were included in the analysis. Seven of the 13 animal studies reported specific diurnal variation in pain intensity, with five of the seven studies reporting a trend toward increased sensitivity to mechanical allodynia or thermal hyperalgesia in the late light to dark phase. All eight studies in human subjects reported a diurnal variation in the intensity of neuropathic pain, where there was an increase in pain intensity through the day with peaks in the late evening and early night hours.

Conclusions

Studies included in this review demonstrated a diurnal variation in the pattern of neuropathic pain that is distinct from the pattern for nociceptive pain. These findings have implications for potential therapeutic strategies for neuropathic pain.
Prediction of sustained biologic and targeted synthetic DMARD-free remission in rheumatoid arthritis patients
Authors: Burkard Theresa , Williams Ross D , Vallejo-Yagüe Enriqueta , Hügle Thomas , Finckh Axel , Kyburz Diego , Burden Andrea M
Published: November 2021

Objectives

The aim was to develop a prediction model of sustained remission after cessation of biologic or targeted synthetic DMARD (b/tsDMARD) in RA.

Methods

We conducted an explorative cohort study among b/tsDMARD RA treatment episode courses stopped owing to remission in the Swiss Clinical Quality Management registry (SCQM; 2008–2019). The outcome was sustained b/tsDMARD-free remission of ≥12 months. We applied logistic regression model selection algorithms using stepwise, forward selection, backward selection and penalized regression to identify patient characteristics predictive of sustained b/tsDMARD-free remission. We compared c-statistics corrected for optimism between models. The three models with the highest c-statistics were validated in new SCQM data until 2020 (validation dataset).

Results

We identified 302 eligible episodes, of which 177 episodes (59%) achieved sustained b/tsDMARD-free remission. Two backward and one forward selection model, with eight, four and seven variables, respectively, obtained the highest c-statistics corrected for optimism of c = 0.72, c = 0.70 and c = 0.69, respectively. In the validation dataset (47 eligible episodes), the models performed with c = 0.99, c = 0.80 and c = 0.74, respectively, and excellent calibration. The best model included the following eight variables (measured at b/tsDMARD stop): RA duration, b/tsDMARD duration, other pain/anti-inflammatory drug use, quality of life (EuroQol), DAS28-ESR score, HAQ score, education, and interactions of RA duration and other pain/anti-inflammatory drug use and of b/tsDMARD duration and HAQ score.

Conclusion

Our results suggest that models with up to eight unique variables may predict sustained b/tsDMARD-free remission with good efficiency. External validation is warranted.
Paradoxically protective effect of glucocorticoids on bone mass and fragility fracture in a large cohort: a cross-sectional study
Authors: Bukhari Marwan , Goodson Nicola , Boers Maarten
Published: November 2021

Objectives

Glucocorticoids (GCs) increase the risk of fracture through reduction in BMD; they may also reduce bone quality, but recent supporting data are scarce. We aimed to confirm these effects in a large population-based cohort.

Methods

We used data from patients referred for first hip and lumbar spine BMD estimation by the sole DXA scanner in the north-west of England between June 2004 and September 2016. We compared the history of fractures and BMD between patients currently on GCs and patients never exposed to GC. A logistic model adjusted for possible confounders.

Results

More than 20 000 subjects were included, 82% female, with mean age 63 (s.d. 13) years; 19% were currently on GCs. The patients on GCs were more often male, with higher BMI, but their age was similar to those not exposed to GC. Surprisingly, patients receiving GCs had ∼2% higher BMD at both sites (P < 0.001) and lower prevalence of (history of) fractures (22% vs 34%; P < 0.001). The corresponding odds ratio was 0.53 (95% CI: 0.49, 0.58); adjustment for age, sex, BMI and the number of indications for scanning did not alter the association.

Conclusion

In this large population-based cohort, current GC use compared with never use was associated with higher bone mass and fewer rather than more fractures after adjusting for confounders. These results might be subject to unmeasured confounding, but for now they do not lend support to a detrimental effect of GCs on bone.
Career Mathways: evaluating a novel initiative aimed at enhancing students’ attitudes towards and appreciation of mathematics
Authors: O’Meara Niamh , Fitzmaurice Olivia , Johnson Patrick
Published: November 2021

The power and value of mathematics cannot be underestimated in today’s society. Thus, it is pertinent that education systems worldwide help students to develop an appreciation of the subject. However, research has shown that students often lose interest in science, technology, engineering and mathematics subjects, particularly mathematics, as they cannot see the relevance of it in their lives. This, in turn, leads to the development of negative attitudes towards mathematics, which have been shown to have a knock-on effect on students’ academic performance, their participation and engagement with and motivation for the subject. The purpose of this paper is to describe and evaluate the impact of an innovative programme, known as Career Mathways, designed to improve secondary school students’ attitudes towards mathematics by highlighting the applicability and usefulness of the subject in a multitude of careers. Career Mathways was piloted in five Irish secondary schools in the 2018/2019 academic year. It involved professionals (n = 13) from a variety of industries sharing insights with students (n = 156) and teachers (n = 6) about how they use mathematics in their day-to-day working lives. Based on these insights, a suite of resources for use in the classroom was developed and implemented with students across the five schools. This paper reports on the impact that this pilot study had on students’ attitudes towards mathematics. The results from pre- and post-student surveys and teacher interviews show that Career Mathways had a moderate but positive influence on students’ appreciation of the usefulness of mathematics and this impact was more profound among lower-achieving students.
Design theories and maintenance technologies of slab tracks for high-speed railways in China: a review
Authors: Ren Juanjuan , Deng Shijie , Zhang Kaiyao , Du Wei , Wu Qinghong
Published: November 2021

The durability and reliability of slab track structures are essential for the long-term safety and stable operation of high-speed railways. In order to provide a solid theoretical basis and technical reference for the advancement of high-speed railway quality, this paper comprehensively discusses design theories of slab track structures, service performance evolution and maintenance technologies, and reviews the innovation happening in the industry. On top of that, the damage evolution, fatigue features and durability of slab tracks, which are highly relevant to serviceability, are summarized, and the future research trend of slab track service behaviours is pointed out. In addition, this paper summarizes the rules of establishing standards for damage maintenance, typical solutions for repairing damage and methods of evaluating the maintenance outcomes that combine field tests and numerical simulations. It also envisions a future direction where advanced testing technologies would assist the evaluation of maintenance effects.
Clinical and biological markers in disease and biologics to treat chronic rhinosinusitis
Authors: Guo Cui-Lian , Wang Chong-Shu , Liu Zheng
Published: November 2021

Purpose of review

Chronic rhinosinusitis (CRS) is a heterogeneous disorder with diverse responses to conventional anti-inflammatory medical and surgical treatments. Even for the newly developed mAbs targeting type 2 (T2) reaction, a considerable number of patients with CRS with nasal polyps (CRSwNP) exhibited unsatisfying response. Identifying patients with a tendency to poor prognosis is critical for selecting targeted therapies to improve the treatment outcome. This review focuses on clinical and biological markers associated with prognosis of CRS patients under conventional medical and surgical treatments and provides an update summary of potential markers for T2 biologics.

Recent findings

Allergic rhinitis, asthma, prior sinus surgery, nasal polyps, tissue eosinophilia and neutrophilia, blood eosinophilia and high levels of Charcot-Leyden crystal, cystatin SN, chemokine (C-C motif) ligand 17, macrophage inflammatory protein-1β and interleukin (IL)-5 in nasal secretions have been associated with poor prognosis in CRS patients under conventional medical and surgical treatments. Blood eosinophil level might be a biomarker for anti-IL-5 (mepolizumab) and anti-IL-5R (benralizumab) biologic in patients with refractory CRSwNP.

Several clinical and biological markers have been associated with poor response to conventional treatments in CRS patients; however, majority of them should be verified by large-scale multicentre studies. More efforts are needed to identify biomarkers for biologics.
Associations Between Privacy-Related Constructs and Depression and Suicide Risk in Health Care Professionals, Trainees, and Students
Authors: Rubanovich Caryn Kseniya , Zisook Sidney , Bloss Cinnamon S.
Published: November 2021

Purpose

The University of California, San Diego screens health care professionals, trainees, and students for depression and suicide risk. Individuals complete a voluntary, anonymous online screening tool and choose whether to provide personal demographic information. This study assessed the relationship between privacy-related constructs and self-rated depression and suicide risk.

Method

The authors analyzed responses to the screening tool collected from January 2018 to December 2019. Measures of depression, suicidal ideation and behaviors, and worry about stigma for seeking mental health services (i.e., privacy-related concern) were gathered. The number of demographic item nonresponses (i.e., age, gender, ethnicity/race, professional position) was operationalized as privacy-related behavior. Linear and logistic regression models were used to determine associations between privacy-related constructs (concern and behavior) and depression and suicide measures.

Results

A total of 1,224 respondents were included. On average, respondents reported mild depression (mean = 9.12, standard deviation = 5.94), but 43% (524/1,224) reported at least moderate depression. One in 5 respondents (248/1,224) reported worry about stigma for seeking mental health services, and more than 17% (212/1,224) skipped at least 1 demographic question. Privacy-related concern was statistically significantly and positively associated with recent depression and suicidal ideation and behaviors (odds ratios [ORs] = 3.13–7.02; 95% confidence interval [CI], 2.23–19.20; P’s < .001) and with lifetime suicide attempts (OR = 1.76; 95% CI, 1.08–2.86; P = .02). Privacy-related behavior was statistically significantly and positively associated with suicide action (OR = 2.23; 95% CI, 1.24–4.02; P = .008).

Conclusions

Privacy-related constructs may be meaningful correlates of mental health as respondents who endorsed these constructs had increased odds of worse depression and suicidal ideation and behaviors. Considering privacy-related constructs may be useful for identifying health care professionals, trainees, and students experiencing distress and in need of imminent mental health resources.
DENOISING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY VOLUMETRIC SCANS USING A DEEP LEARNING MODEL
Authors: Ledesma-Gil Gerardo , Mao Zaixing , Liu Jonathan , Spaide Richard F.
Published: November 2021

Purpose:

To evaluate the use of a deep learning noise reduction model on swept source optical coherence tomography volumetric scans.

Methods:

Three groups of images including single-line highly averaged foveal scans (averaged images), foveal B-scans from volumetric scans using no averaging (unaveraged images), and deep learning denoised versions of the latter (denoised images) were obtained. We evaluated the potential increase in the signal-to-noise ratio by evaluating the contrast-to-noise ratio of the resultant images and measured the multiscale structural similarity index to determine whether the unaveraged and denoised images held true in structure to the averaged images. We evaluated the practical effects of denoising on a popular metric of choroidal vascularity known as the choroidal vascularity index.

Results:

Ten eyes of 10 subjects with a mean age of 31 years (range 24–64 years) were evaluated. The deep choroidal contrast-to-noise ratio mean values of the averaged and denoised image groups were similar (7.06 vs. 6.81, P = 0.75), and both groups had better maximum contrast-to-noise ratio mean values (27.65 and 46.34) than the unaveraged group (14.75; P = 0.001 and P < 0.001, respectively). The mean multiscale structural similarity index of the average–denoised images was significantly higher than the one from the averaged–-unaveraged images (0.85 vs. 0.61, P < 0.001). Choroidal vascularity index values from averaged and denoised images were similar (71.81 vs. 71.16, P = 0.554).

Conclusion:

Using three different metrics, we demonstrated that the deep learning denoising model can produce high-quality images that emulate, and may exceed, the quality of highly averaged scans.
Predictive and prognostic factors for outcome of microvascular decompression in trigeminal neuralgia
Authors: Huang Chih-Wei , Yang Meng-Yin , Cheng Wen-Yu , Pan Szu-Yen , Wang Chia-Lin , Lai Wei-Yi , Lin Tzu-Wei , Liu Szu-Yuan , Huang Yu-Fen , Lai Chin-ming , Shen Chiung-Chyi
Published: November 2021

Background:

Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock–like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes.

Methods:

This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test.

Results:

A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann–Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study.

Conclusion:

In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.
Robotic bronchoscopy and future directions of interventional pulmonology
Authors: Folch Erik , Mittal Abhinav , Oberg Catherine
Published: November 2021

Purpose of review

To describe the emerging field of robotic bronchoscopy within advanced diagnostic bronchoscopy. We review the literature available for these two novel platforms to highlight their differences and discuss the impact on future directions.

Recent findings

There are two distinct technologies both known as robotic bronchoscopy. The Monarch robotic-assisted bronchoscopy is based on electromagnetic guidance whereas the Ion robotic-assisted bronchoscopy is founded on shape sensing technology. Although there is ongoing work to explore the capabilities of these systems, studies have shown that both are safe modalities. Furthermore, both hold promise to improve diagnostic yield and may eventually pave the way for therapeutic bronchoscopic ablation in the future.

Although both platforms fall under the umbrella term of robotic-assisted bronchoscopy, the Monarch and Ion systems are quite unique in their technology. Thus far, both have demonstrated safety, and early data shows promising results for improved diagnostic yield compared to previously advanced bronchoscopy modalities, especially when combined with advanced confirmatory imaging. Future directions may include bronchoscopic ablation of peripheral lesions given the stability and reach of these platforms.
Innovative Hospital-Based Pediatric Virtual Learning for Nursing Students
Authors: Walsh Heather , Brown Nina , Nicholson Laura , King Simmy
Published: November 2021

Background/Problem:

Specialty clinical sites, including pediatrics, are historically scarce in prelicensure nursing education.

Approach:

Simulation educators developed the Pediatric Virtual Clinical Learning Series (PVCLS) containing 4 virtual learning modules designed to enhance knowledge and skills of prelicensure nursing students in clinical pediatric care. Topics included documentation, rapid response, code blue, and a pediatric case. The learning sessions were initially offered as synchronous virtual classes and were then posted on our e-learning platform to serve as enduring asynchronous material. The target audience was nursing students and faculty from regional and nationally affiliated nursing schools with the pediatric hospital.

Outcomes:

Faculty and 185 nursing students participated in the synchronous or asynchronous learning sessions. Students' ratings that the virtual classes met their personal expectations were 4.02 to 4.56 of 5 for the synchronous sessions and 3.41 to 3.58 of 4 for the asynchronous sessions.

Conclusions:

The PVCLS provided both synchronous and asynchronous learning experiences to fill a widening knowledge gap in pediatrics.
Unraveling the Cognitive-Motor Interaction in Individuals With Amnestic Mild Cognitive Impairment
Authors: Gaillardin Florence , Bier Jean-Christophe , De Breucker Sandra , Baudry Stéphane
Published: November 2021

Purpose:

This study aimed to determine whether increasing the contribution of executive functions worsens dual-task performance in individuals with amnestic mild cognitive impairment (aMCI).

Methods:

Fourteen individuals with aMCI (mean [SD]: 74 [4] years) and 19 control adults (71 [5] years) recalled a list of letters in the order of presentation (SPAN-O) or in alphabetic order (SPAN-A) while ascending or descending a 3-step staircase. Dual-task cost (DTC) represented the average decrement of motor and cognitive performances during dual tasks, with greater DTC indicating worse performance.

Results:

SPAN-A (P < 0.001) and stair descent (P = 0.023) increased the DTC in both groups compared with SPAN-O and stair ascent. Furthermore, individuals with aMCI had a greater DTC (93.4 [41.2]%) than the control group (48.3 [27.9]%) for SPAN-A (P < 0.001). Dual-task cost was also greater in descent (76.6 [42.1]%) than ascent (64.0 [34.5]%) in individuals with aMCI (P = 0.024) but not in the control group (P = 0.99). Significant negative partial correlations (β < −0.39; P < 0.05) were found between Montreal Cognitive Assessment score and DTC, while controlling for age and physical function.

Discussion and Conclusions:

A greater DTC in individuals with aMCI when the cognitive task requires working memory (SPAN-A) or during complex locomotor task (descent) suggests that aMCI impedes the capacity to perform 2 tasks simultaneously when higher-order cognitive processes are challenged. Furthermore, a greater DTC in our dual-task situations appears to reflect cognitive decline, as assessed by the Montreal Cognitive Assessment score. Overall, this study indicates that increasing the contribution of executive functions worsens the cognitive-motor interaction in individuals with aMCI.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A375).
A Retrospective Review of Serious Surgical Incidents in 5 Large UK Teaching Hospitals: A System-Based Approach
Authors: Serou Naresh , Slight Robert D. , Husband Andy K. , Forrest Simon P. , Slight Sarah P.
Published: November 2021

Objectives

Surgical incidents are the most common serious patient safety incidents worldwide. We conducted a review of serious surgical incidents recorded in 5 large teaching hospitals located in one London NHS trust to identify possible contributing factors and propose recommendations for safer healthcare systems.

Methods

We searched the Datix system for all serious surgical incidents that occurred in any operating room, excluding critical care departments, and were recorded between October 2014 and December 2016. We used the London Protocol system analysis framework, which involved a 2-stage approach. A brief description of each incident was produced, and an expert panel analyzed these incidents to identify the most likely contributing factors and what changes should be recommended.

Results

One thousand fifty-one surgical incidents were recorded, 14 of which were categorized as “serious” with contributing factors relating to task, equipment and resources, teamwork, work environmental, and organizational and management. Operating room protocols were found to be unavailable, outdated, or not followed correctly in 8 incidents studied. The World Health Organization surgical safety checklist was not adhered to in 8 incidents, with the surgical and anesthetic team not informed about faulty equipment or product shortages before surgery. The lack of effective communication within multidisciplinary teams and inadequate medical staffing levels were perceived to have contributed.

Conclusions

Multiple factors contributed to the occurrence of serious surgical incidents, many of which related to human failures and faulty equipment. The use of faulty equipment needs to be recognized as a major risk within departments and promptly addressed.
Back squat mechanics in persons with a unilateral transtibial amputation: A case study
Authors: Cooper Kinyata J. , Fain AuraLea , Lee Childers Walter
Published: November 2021

Case description:

A 30-year-old person with a unilateral transtibial amputation (TTAmp) was assessed performing an Olympic-style back squat with an energy storage and return prosthetic foot.

Objective:

Determine joint-level movement strategies of an individual with TTAmp while performing an Olympic-style back squat.

Study design:

Case study design.

Treatment:

Back squat mechanics are evaluated in an individual with TTAmp by comparing the contribution of the ankle, knee, and hip joint to total positive and negative amputated and sound limb work.

Outcomes:

The hip joint was the greatest contributor to total positive limb work compared with the knee and ankle, respectively, in the amputated (55.0% hip vs. 30.8% knee, P < 0.001; vs. 14.2% ankle, P = 0.001) and sound limbs (52.2% hip vs. 38.9% knee, P < 0.001; vs. 8.9% ankle, P < 0.001). The hip joint was the greatest contributor to total negative limb work compared with the ankle in both the amputated (51.0% hip vs. 15.9% ankle, P < 0.001) and sound limbs (47.3% hip vs. 10.0% ankle, P < 0.001) and the knee in the amputated limb (51.0% hip vs. 32.5% knee, P < 0.001). Ankle joint power demonstrated an atypical bimodal negative/positive/negative/positive pattern.

Conclusion:

The individual with TTAmp used a hip-dominant joint strategy in both the amputated and sound limbs while demonstrating more potential to optimize the prosthetic foot’s energy storage and return capabilities when performing a back squat.
Adjustable Medial Epicanthoplasty Using a Rotational Flap for Epiblepharon Repair
Authors: Mimura Masashi , Sato Yohei , Fujita Yasushi , Korn Bobby S. , Kikkawa Don O. , Oku Hidehiro , Sato Bunpei , Ikeda Tsunehiko
Published: November 2021

This report aimed to introduce the new adjustable rotational skin flap for epicanthoplasty in combination with traditional epiblepharon repair by the modified Hotz procedure. This retrospective study involved 25 consecutive patients with superficial punctate keratitis secondary to epiblepharon complicated with epicanthal fold who underwent the combined surgery between 2019 and 2020. The mean patient age was 11.4 years in this study with a median follow-up was 8months (range, 3–12months). The rationale of the surgery was to release vertical tension of the eyelids by dissecting dense connective tissue beneath the epicanthal fold and to form a new medial canthus using a rotational skin flap supplied by the redundant the upper and/or lower eyelid skin excised during the epiblepharon repair. Postsurgical resolution ofsuperficial punctate keratitis and patient satisfaction was achieved in all patients. Additionally, there were no complications, and no revisional surgery was required in all patients for a median 8 months follow-up period. Utilizing a rotational skin flap during epiblepharon repair is a useful adjunct during epicanthoplasty surgery. This modification is well tolerated and allows for intraoperative adjustment, whereas minimizing scarring and allowing for improved tissue relaxation.
Outcomes of Treatment With Manipulative Reduction Combine With the Disc-condyle Repositioning Splint in Acute Anterior Disc Displacement Without Reduction
Authors: Cheng Hui Na , Lee Lee Mui , Deng Yong Qiang , Di Zhang Dan , Yao Wei , Zhu Yao Min
Published: November 2021

In this report, the authors describe a case of the acute anterior disc displacement without reduction treated by manipulative reduction combined with the disc-condyle repositioning splint to improve the limited mouth opening and relieve the pain, including diagnostic images and treatment performed.
Recent zoonotic spillover and tropism shift of a Canine Coronavirus is associated with relaxed selection and putative loss of function in NTD subdomain of spike protein
Authors: Zehr Jordan D. , Kosakovsky Pond Sergei L. , Martin Darren P. , Ceres Kristina , Whittaker Gary R. , Goodman Laura B. , Stanhope Michael J.
Published: November 2021

A recent study reported the occurrence of Canine Coronavirus (CCoV) in nasopharyngeal swabs from a small number of patients hospitalized with pneumonia during a 2017-18 period in Sarawak, Malaysia. Because the genome sequence for one of these isolates is available, we conducted comparative evolutionary analyses of the spike gene of this strain (CCoV-HuPn-2018), with other available Alphacoronavirus 1 spike sequences. The most N-terminus subdomain (0-domain) of the CCoV-HuPn-2018 spike protein has sequence similarity to Transmissible Gastroenteritis Virus (TGEV) and CCoV2b strains, but not to other members of the type II Alphacoronaviruses (i.e., CCoV2a and Feline CoV2-FCoV2). This 0-domain in CCoV-HuPn-2018 has evidence for relaxed selection pressure, an increased rate of molecular evolution, and a number of unique amino acid substitutions relative to CCoV2b and TGEV sequences. A region of the 0-domain determined to be key to sialic acid binding and pathogenesis in TGEV had clear differences in amino acid sequences in CCoV-HuPn-2018 relative to both CCoV2b (enteric) and TGEV (enteric and respiratory). The 0-domain of CCoV-HuPn-2018 also had several sites inferred to be under positive diversifying selection, including sites within the signal peptide. Downstream of the 0-domain, FCoV2 shared sequence similarity to the CCoV2b and TGEV sequences, with analyses of this larger alignment identifying positively selected sites in the putative Receptor Binding Domain (RBD) and Connector Domain (CD). Recombination analyses strongly implicated a particular FCoV2 strain in the recombinant history of CCoV-HuPn-2018 with molecular divergence times estimated at around 60 years ago. We hypothesize that CCoV-HuPn-2018 had an enteric origin, but that it has lost that particular tropism, because of mutations in the sialic acid binding region of the spike 0-domain. As selection pressure on this region was reduced, the virus evolved a respiratory tropism, analogous to other Alphacoronavirus 1, such as Porcine Respiratory Coronavirus (PRCV), that have lost this region entirely. We also suggest that signals of positive selection in the signal peptide as well as other changes in the 0-domain of CCoV-HuPn-2018 could represent an adaptive role in this new host and that this could be in part due to the different spatial distribution of the N-linked glycan repertoire for this strain.
SARS-CoV-2 RdRp uses NDPs as a substrate and is able to incorporate NHC into RNA from diphosphate form molnupiravir
Authors: Wang Maofeng , Wu Cancan , Liu Nan , Zhang Fengyu , Dong Hongjie , Wang Shuai , Chen Min , Jiang Xiaoqiong , Gu Lichuan
Published: November 2021

The coronavirus disease 2019 (COVID-19) has been ravaging throughout the world for more than two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Here, we reveal that RdRp can recognize and utilize nucleoside diphosphates (NDPs) as a substrate to synthesize RNAs with an efficiency of about two thirds of using nucleoside triphosphates (NTPs) as a substrate. NDPs incorporation is also template-specific and has high fidelity. Moreover, RdRp can incorporate β-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir (MDP) as a substrate. We also observed that MDP is a better substrate for RdRp than the triphosphate form molnupiravir (MTP).
Tuning spherical cells into kinking helices in wall-less bacteria
Authors: Lartigue Carole , Lambert Bastien , Rideau Fabien , Decossas Marion , Hillion Mélanie , Douliez Jean-Paul , Hardouin Julie , Lambert Olivier , Blanchard Alain , Béven Laure
Published: November 2021

In bacteria, cell shape is determined and maintained through a complex interplay between the peptidoglycan cell wall and cytoplasmic filaments made of polymerized MreB. Spiroplasma species, members of the Mollicutes class, challenge this general understanding because they are characterized by a helical cell shape and motility without a cell wall. This specificity is thought to rely on five MreB isoforms and a specific fibril protein. In this study, combinations of these five MreBs and of the fibril from Spiroplasma citri were expressed in another Mollicutes, Mycoplasma capricolum. Mycoplasma cells that were initially pleomorphic, mostly spherical, turned into helices when MreBs and fibrils were expressed in this heterologous host. The fibril protein was essential neither for helicity nor for cell movements. The isoform MreB5 had a special role as it was sufficient to confer helicity and motility to the mycoplasma cells. Cryo-electron microscopy confirmed the association of MreBs and fibril-based cytoskeleton with the plasma membrane, suggesting a direct effect on the membrane curvature. Finally, the heterologous expression of these proteins, MreBs and fibril, made it possible to reproduce the kink-like motility of spiroplasmas without providing the ability of cell movement in liquid broth. We suggest that other Spiroplasma components, not yet identified, are required for swimming, a hypothesis that could be evaluated in future studies using the same model.
Lattice-based microenvironmental uncertainty driven phenotypic decision-making: a comparison with Notch-Delta-Jagged signaling
Authors: Pujar Aditi Ajith , Barua Arnab , Singh Divyoj , Roy Ushasi , Jolly Mohit Kumar , Hatzikirou Haralampos
Published: November 2021

Phenotypic decision-making is a process of determining important phenotypes in accordance with the available microenvironmental information. Although phenotypic decision at the level of a single cell has been precisely studied, but the knowledge is still imperceptible at the multicellular level. How cells sense their environment and adapt? How single cells change their phenotype in a multicellular complex environment (without knowing the interactions among the cells), is still a rheotorical question. To unravel the fragmental story of multicellular decision-making, Least microEnvironmental Uncertainty Principle (LEUP) was refined and applied in this context. To address this set of questions, we use variational principle to grasp the role of sensitivity, build a LEUP driven agent-based model on a lattice which solely hinges on microenvironmental information and investigate the parallels in a well-known biological system, viz., Notch-Delta-Jagged signaling pathway. The analyses of this model led us to interesting spatiotemporal patterns in a population of cells, responsive to the sensitivity parameter and the radius of interaction. This resembles the tissue-level pattern of a population of cells interacting via Notch-Delta-Jagged signaling pathway in some parameter regimes.
The response network of HSP70 defines vulnerabilities in cancer cells with the inhibited proteasome
Authors: Oroń Magdalena , Grochowski Marcin , Jaiswar Akanksha , Legierska Justyna , Jastrzębski Kamil , Nowak-Niezgoda Magdalena , Kołos Małgorzata , Kaźmierczak Wojciech , Olesiński Tomasz , Lenarcik Małgorzata , Cybulska Magdalena , Mikuła Michał , Żylicz Alicja , Miączyńska Marta , Zettl Katherina , Wiśniewski Jacek R. , Walerych Dawid
Published: November 2021

Human neoplasias are often addicted to the proteasome machinery. However, cancers have evolved efficient response mechanisms to overcome proteasome inhibition with bortezomib and carfilzomib - drugs approved for multiple myeloma treatment. To understand these responses we investigated proteome changes upon the proteasome inhibition with carfilzomib - in multiple myeloma, normal fibroblasts, and cancers of lung, colon, and pancreas. A pathway-oriented siRNA screen based on the proteomics results showed that molecular chaperones, autophagy- and endocytosis-related proteins are cancer-specific vulnerabilities combined with carfilzomib. Targeting of HSPA1A/B (HSP70 family chaperones) most specifically sensitized cancer cells and patient-derived organoids to the proteasome inhibition. A high level of HSPA1A/B mRNA correlated with a low proteasome activity in cancer patient tissues and is a risk factor in cancer patients with a low proteasome expression. Mechanistically, HSPA1A/B governed autophagy, unfolded protein response, endocytic trafficking, and chaperoned the proteasome machinery, suppressing the effect of the proteasome inhibition, but did not control the NRF1/2-driven proteasome subunit transcriptional bounce-back. Consequently, downregulation of NRF1 most specifically decreased the viability of cancer cells with the inhibited proteasome and HSP70.
Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization
Authors: Neginskaya M.A. , Morris S.E. , Pavlov E.V.
Published: November 2021

A sudden increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the opening of the Cyclosporin A (CSA) dependent calcium-induced pore, the Permeability Transition Pore (PTP). The molecular details of PTP are incompletely understood. We utilized a combination of holographic and fluorescent microscopy to assess the contribution of the ATP synthase and Adenine Nucleotide Translocator (ANT) towards PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. Further, we found that in wild-type cells calcium induced CSA-sensitive depolarization precedes opening of the PTP, which occurred until after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high conductance PTP but not depolarization, which presumably occurs through activation of the low conductance PT, which has a molecular nature that is different from both complexes.