bluuebunny/crossref_metadata_2025 huggingface dataset:
SWEAT ICU—An Observational Study of Physician Workload and the Association of Physician Outcomes in Academic ICUs
Authors: Agarwal Ankita , Chen Jen-Ting , Coopersmith Craig M. , Denson Joshua L. , Dickert Neal W. , Ferrante Lauren E. , Gershengorn Hayley B. , Gosine Adhiraj D. , Hayward Bradley J. , Kaur Navneet , Khan Akram , Lamberton Courtney , Landsittel Douglas , Lyons Patrick G. , Mikkelsen Mark E. , Nadig Nandita R. , Pietropaoli Anthony P. , Poole Brian R. , Viglianti Elizabeth M. , Sevransky Jonathan E. ,   on behalf of SCCM Discovery Network
Published: October 2022

OBJECTIVES:

The optimal staffing model for physicians in the ICU is unknown. Patient-to-intensivist ratios may offer a simple measure of workload and be associated with patient mortality and physician burnout. To evaluate the association of physician workload, as measured by the patient-to-intensivist ratio, with physician burnout and patient mortality.

DESIGN:

Cross-sectional observational study.

SETTING:

Fourteen academic centers in the United States from August 2020 to July 2021.

SUBJECTS:

We enrolled ICU physicians and collected data on adult ICU patients under the physician’s care on the single physician-selected study day for each physician.

MEASUREMENTS and MAIN RESULTS:

The primary exposure was workload (self-reported number of patients’ physician was responsible for) modeled as high (>14 patients) and low (≤14 patients). The primary outcome was burnout, measured by the Well-Being Index. The secondary outcome measure was 28-day patient mortality. We calculated odds ratio for burnout and patient outcomes using a multivariable logistic regression model and a binomial mixed effects model, respectively. We enrolled 122 physicians from 62 ICUs. The median patient-to-intensivist ratio was 12 (interquartile range, 10–14), and the overall prevalence of burnout was 26.4% (n = 32). Intensivist workload was not independently associated with burnout (adjusted odds ratio, 0.74; 95% CI, 0.24–2.23). Of 1,322 patients, 679 (52%) were discharged alive from the hospital, 257 (19%) remained hospitalized, and 347 (26%) were deceased by day 28; 28-day outcomes were unknown for 39 of patients (3%). Intensivist workload was not independently associated with 28-day patient mortality (adjusted odds ratio, 1.33; 95% CI, 0.92–1.91).

CONCLUSIONS:

In our cohort, approximately one in four physicians experienced burnout on the study day. There was no relationship be- tween workload as measured by patient-to-intensivist ratio and burnout. Factors other than the number of patients may be important drivers of burnout among ICU physicians.
Trends in mortality of liver disease due to hepatitis B in China from 1990 to 2019: findings from the Global Burden of Disease Study
Authors: Cao Guiying , Liu Jue , Liu Min
Published: October 2022

Background:

Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease. China has the world's largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization (WHO) of eliminating hepatitis B virus (HBV) as a global health threat by 2030. This study aimed to analyze data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO's goal.

Methods:

Annual deaths and age-standardized mortality rates (ASMRs) of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019. We calculated the percentage changes in deaths and estimated annual percentage changes (EAPCs) of ASMRs of liver disease due to hepatitis B.

Results:

In China, deaths of total liver disease due to hepatitis B decreased by 29.13% from 229 thousand in 2016 to 162 thousand in 2019, and ASMR decreased by an average of 4.92% (95% confidence interval [CI]: 4.45–5.39%) per year in this period. For the spectrum of liver disease due to hepatitis B, deaths decreased by 74.83%, 34.71%, and 23.34% for acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer from 1990 to 2019, respectively, and ASMRs of acute hepatitis (EAPC = –7.63; 95% CI: –8.25, –7.00), cirrhosis and other chronic liver diseases (EAPC = –4.15; 95% CI: –4.66, –3.65), and liver cancer (EAPC = –5.17; 95% CI: –6.00, –4.33) decreased between 1990 and 2019. The proportions of older adults aged ≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019. Deaths of liver cancer due to hepatitis B increased by 7.05% from 2015 to 2019.

Conclusions:

Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019, China still faces challenges in achieving the WHO's goal of eliminating HBV as a public threat by 2030. Therefore, efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B, especially of liver cancer due to hepatitis B, are warranted in China.
Auricular Total Reconstruction with Radial Forearm Prelaminated Flap Assisted by 3D Surface Imaging and 3D Printing
Authors: Rendón-Medina Marco Aurelio , Hanson-Viana Erik , Arias-Salazar Leidy , Rojas-Ortiz Jorge Arturo , Mendoza-Velez Maria de los Angeles , Hernandez-Ordoñez Rubén , Vázquez-Morales Hecly Lya , Pacheco-López Ricardo C.
Published: October 2022

The anatomic position of the auricle leaves it vulnerable to traumatic lesions. In most cases, the best reconstructive outcome is accomplished using a temporoparietal flap with a costal cartilage frame and a partial thickness skin graft. Exceptional cases may require different approaches because the reconstructive goals could be more structural than aesthetic. An important factor in this regard is the mechanical properties of the skin that will provide coverage. This study aimed to share a particular case of total auricular reconstruction assisted by 3D surface imaging and 3D printing in a radial forearm free flap. We present a 58-year-old man with a history of having tympanic barotrauma causing hearing loss, burdening him with the use of auricular devices for hearing assistance. Seven days before presenting for the initial treatment, he sustained ear trauma while performing mechanical reparations in a car. The wheel was activated, causing a total amputation of the right ear. He first went to another hospital‚ where they performed primary closure and then referred him to our unit. The team performed a prelaminated radial forearm free flap assisted by 3D scanning and planning. A detailed comparison between the left ear and the result of the reconstruction was measured and described. The radial forearm prelaminated free flap is a viable structural alternative with the disadvantage of poor auricular definition in some cases.
Catheter ablation of atrial fibrillation in heart failure with impaired systolic function: An updated meta-analysis of randomized controlled trials
Authors: Chang Ting-Yung , Chao Tze-Fan , Lin Chin-Yu , Lin Yenn-Jiang , Chang Shih-Lin , Lo Li-Wei , Hu Yu-Feng , Chung Fa-Po , Chen Shih-Ann
Published: October 2022

Background:

The recent Atrial Fibrillation Management in Congestive Heart Failure With Ablation trial did not reveal any benefit of catheter ablation in patients with atrial fibrillation (AF), advanced heart failure (HF), and severely reduced left ventricular ejection fraction (LVEF). We hypothesized that radiofrequency catheter ablation (RFCA) could improve outcomes in HF patients with AF and impaired left ventricular systolic function (LVEF <50%) as compared with only medical therapy.

Methods:

We searched the literature for randomized clinical trials (RCTs) that compared RFCA to medical therapy in this population.

Results:

Compared with the medical therapy group, the RFCA group had significantly less all-cause mortality, HF hospitalization, and AF recurrence rates. The RFCA group had significantly higher peak oxygen consumption (VO2max), a better quality of life (Minnesota Living with Heart Failure Questionnaire score), and improved LVEF. However, RFCA for AF failed to reduce all-cause mortality in a specific meta-analysis of four RCTs that enrolled patients with LVEF ≤35%.

Conclusion:

Compared with medical therapy, RFCA for AF in the setting of HF with impaired systolic function is associated with better clinical (HF hospitalization and all-cause mortality), structural (LVEF improvement), functional (VO2max), and quality of life outcomes. However, RFCA for AF failed to reduce all-cause mortality in RCTs that enrolled patients with LVEF ≤35% and thereby indicated the necessary stratification to identify patients who may benefit more from RFCA.
Trends in Gastroparesis Management
Authors: Tanner Samuel E. , Kurin Michael , Shahsavari Dariush , Malik Zubair , Parkman Henry P.
Published: October 2022

Background:

There is little consensus on the medical management of gastroparesis, a disorder characterized by delayed gastric emptying with symptoms of early satiety, nausea, vomiting, and upper abdominal pain.

Goals:

We utilized population-level data to: (1) describe the prevalence of different pharmacological and nonpharmacological therapies in patients with gastroparesis; and (2) trend the prevalence of these therapies from 2010 to 2020.

Study:

More than 59 million unique medical records across 26 US-based major health care systems were surveyed using the Explorys platform to identify a cohort of adults with gastroparesis who completed both a gastric emptying study and upper endoscopy or upper gastrointestinal tract imaging. Prevalence of antiemetic, prokinetic, neuromodulator prescriptions, and surgical therapies for gastroparesis were searched within this cohort and trended annually from 2010 to 2020.

Results:

Antiemetics (72% of patients), prokinetics (47%), and neuromodulators (75% of patients, 44% of patients without a concomitant psychiatric or diabetic peripheral neuropathy diagnosis) were all commonly used in the treatment of patients with gastroparesis. From 2010 to 2020, there was an increase in the prevalence of antiemetic and neuromodulator prescriptions (36.4% to 57.6%, P<0.001 and 47.0% to 66.9%, P<0.001, respectively), whereas the prevalence of prokinetics remained relatively constant (31.8% to 31.6%, P=0.52). Procedural and surgical treatments were used in 5% of gastroparesis patients.

Conclusions:

Treatments for gastroparesis have changed over the last decade: antiemetic and neuromodulator use has increased whereas prokinetic use has remained constant. This practice pattern may reflect the growing number and availability of antiemetics and neuromodulators and the small number and known side effects of prokinetics.
Baseline Patient-reported Symptoms Less Predictive Than MM-SES-CD for Endoscopic Remission in Crohn’s Disease
Authors: Narula Neeraj , Wong Emily C.L. , Aruljothy Achuthan , Dulai Parambir S. , Colombel Jean-Frederic , Marshall John K. , Ferrante Marc , Reinisch Walter
Published: October 2022

Background:

This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn’s disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (ER).

Methods:

This post hoc analysis of 2 clinical trials of infliximab in CD included 601 patients and evaluated baseline PRS variables (abdominal pain, stool frequency, and general well-being) as measured by the Crohn’s disease activity index and their association with 6-month clinical remission (CR) (Crohn’s Disease Activity Index<150), corticosteroid-free CR, and week 26/54 ER (absence of mucosal ulceration). Logistic regression models assessed the relationships between PRS and outcomes of interest. Receiver operating characteristic curve analyses compared the sensitivity and specificity of the different baseline PRS compared with baseline endoscopic scores for achievement of ER at weeks 26 and 54.

Results:

No difference was found comparing patients with higher baseline PRS to those with lower PRS in achieving 6-month CR, 6-month corticosteroid-free CR, or week 26/54 ER. Modified multiplier of the SES-CD (MM-SES-CD) at baseline demonstrated a significant ability to predict week 54 ER (area under the curve, 0.71; 95% CI 0.65-0.78; P=0.017).

Conclusions:

Baseline PRS in CD is not prognostic of clinical or endoscopic response. In contrast, active endoscopic disease as measured by the MM-SES-CD, more accurately predicts endoscopic outcomes. Endoscopic scores such as the MM-SES-CD may be considered for selection criteria and as a primary outcome of interest in CD trials, with PRS as a co-primary or secondary endpoint.
Efficacy and Long-term Safety of Telbivudine Usage During Second or Third Trimester in Hepatitis B Surface Antigen Positive Mothers With High Viral Load
Authors: Jiang Hongxiu , Ye Xiajun , Chen Chao , Zhou Guanlun , Han Guorong
Published: October 2022

Goals:

The study is to evaluate the efficacy and long-term safety of telbivudine (LdT) usage for hepatitis B surface antigen (HBsAg) positive pregnant women with high viral load.

Background:

The efficacy and safety of LdT during pregnancy were not assessed from a long-term perspective.

Study:

HBsAg-positive pregnant women were enrolled and grouped according to antiviral initiation time. Group A (n=100) and group B (n=100) were treated with LdT initiated in the second or third trimester. Group C (n=90) received no antiviral treatment. The efficacy and safety of LdT treatment were compared and infants were followed-up at 1, 5, and 10 years. Denver developmental screening test was conducted at 5 years.

Results:

Viral loads before delivery in LdT-treated groups were lower than that in group C and group A was lower than that in group B (P<0.001). No infants in LdT-treated groups were infected whereas 8.8% (8/90) infants in group C had positive HBsAg (χ2=23.20,P<0.001). All LdT-treated mothers were well tolerated and no LdT-related adverse events in infants were reported. Part of the physical growth index of infants was higher than Chinese standard values (SV) and showed significant differences. In groups A and B, the developmental screening test qualified rate of 100% (48/48) and 97.96% (48/49) showed no significant difference compared with 92% in normal Chinese children (χ2=5.72,P=0.06).

Conclusions:

Treatment initiated during the second trimester could strengthen the success of mother-to-child transmission blockage. LdT treatment during pregnancy is safe for both mothers and infants in the long term.
Pediatric strength training: benefits, concerns, and current trends
Authors: Wang Xihang , Dubrosa Fiona , O’Connor Mary , Sangiuolo Kara , Milanaik Ruth L.
Published: October 2022

Purpose of review

With the advent of social media combined with several large-scale promotions by nationwide gym chains, pediatric interest in strength training has reached new heights during the past few years. While this is a healthy way for young gym users to build strength and stay active, there are significant risks associated with improper utilization of exercise resources. Lack of adult supervision and guidance in the gym can lead to physical injury, inappropriate use of supplements, and body image issues. The purpose of this review is to provide pediatricians with up-to-date information about well tolerated exercise practices for pubertal and prepubertal youth.

Recent findings

Current exercise trends may negatively impact both the physical and mental health of participants. Various physical injuries may occur when adolescents use gym equipment incorrectly under inadequate adult supervision. Use of unproven equipment such as waist trainers may cause bodily injury, and social media content on exercising and weight loss can negatively influence adolescent body image. Potential consequences include low self-esteem and uncommon body dysmorphic disorders, such as muscle dysmorphia. Further, the intense marketing of supplements can induce pediatric gym users to engage in inappropriate consumption behaviors. The increasing accessibility of commercial gyms to youth has increased the potential for children and adolescents to be exposed to such physical and mental health hazards.

Greater knowledge regarding strength training techniques will help pediatricians guide their patients toward well tolerated and healthy gym habits. Caregivers and medical professionals should recognize the necessity of supervision, as well as the dangers of incorrect equipment use and unsafe trends to mitigate risks and maximize benefits of pediatric gym use.
Temperature change during laser upper-tract endourological procedures: current evidence and future perspective
Authors: Tokas Theodoros , Rice Patrick , Seitz Christian , Gauhar Vineet , Somani Bhaskar
Published: October 2022

Purpose of review

To examine the most recent data on temperatures produced during laser lithotripsy and to provide several strategies for maintaining lower values and reducing the risk of complications during endourological treatment.

Recent findings

Endourologists have access to a wide range of alternatives with the help of the holmium: yttrium-aluminum-garnet (Ho:YAG), thulium: yttrium-aluminum-garnet (TM:YAG), and thulium fiber laser (TFL) that compose a robust and adaptable laser lithotripsy armamentarium. Nevertheless, the threat of thermal damage increases as the local temperature rises with high total power. Most endourologists are not familiar with normal and pathological temperature ranges, how elevated temperatures affect perioperative problems, or how to avoid them.

Increased temperatures experienced during laser lithotripsy may affect the course of the healing process. All lasers display a safe temperature profile at energies below 40 W. At equal power settings, Ho:YAG, Tm:YAG, and TFL lasers change the temperature comparably. Shorter on/off laser activation intervals, chilled irrigation, open irrigation systems, and UASs all aid in maintaining acceptable temperatures.
Pregnant Women's Perception of Secondhand Smoke Exposure
Authors: Artzi-Medvedik Rada , Mohamed Nourhan , Chertok Ilana R. Azulay
Published: October 2022

Background:

Birth outcomes including low birth weight, preterm birth, and delayed infant neurodevelopment are associated with secondhand smoke exposure while pregnant. The purpose of the study was to explore pregnant women's perspectives on secondhand smoke exposure to understand their experience and inform recommendations.

Study Design and Methods:

Qualitative semistructured interviews were conducted with 15 secondhand smoke-exposed pregnant women in the United States.

Results:

Four primary themes were identified: feeling powerless, trapped, and discomfort; enhancing women's self-advocacy and initiative; having conflicting feelings about secondhand smoke exposure; and desiring professional advice and education. Women expressed concern about prenatal secondhand smoke exposure, although they felt unable to request that people refrain from smoking in their presence or personal space. Women's strategies to minimize secondhand smoke exposure often involved their own social isolation. Women described sources of support, educational needs, and desire for practical advice in secondhand smoke avoidance.

Clinical Implications:

Findings underscore the role of nurses working with pregnant women living with household members who smoke to educate women about secondhand smoke risks and strategies for avoidance and to enhance women's self-confidence in advocating for themselves to reduce their exposure.
Distinct Uroplakin II Staining Pattern in Apocrine Breast Carcinoma
Authors: van Pel Derek M. , Pors Jennifer , Yuen Eddie , Chan Rebecca , Kos Zuzana , Hayes Malcolm M. , Wang Gang
Published: October 2022

Uroplakin II (UPII) has been shown as a highly specific marker of urothelial carcinoma; however, it can also stain subtypes of apocrine-differentiated breast carcinoma. Given that urothelium and breast epithelium share other common immunohistochemical markers, such as CK7 and GATA3, this can lead to a potential diagnostic pitfall. We stained a cohort of triple-negative breast cancer with UPII. Compared with the diffuse, cytoplasmic staining in urothelial carcinoma, UPII was positive in 38.9% of apocrine carcinoma (7/18) with a course, granular cytoplasmic staining pattern and negative in all nonapocrine triple-negative breast cancer cases. Furthermore, the same staining pattern was present in all apocrine metaplasia of the breast (4/4) and apocrine sweat glands in normal skin (6/6). This distinct subcellular localization of UPII staining in breast carcinoma can offer a potential solution to the above diagnostic pitfall.
Characterizing Ventilatory Muscle Dysfunction in Inclusion Body Myositis
Authors: Brokamp Gabrielle , Hurst Lauren , Hartog Leigh , Vilson Ferdinand , Reynolds Jerold , Elsheikh Bakri H. , Arnold W. David
Published: October 2022

Objective

Investigation of the frequency and progression of ventilatory muscle dysfunction in patients with inclusion body myositis (IBM), the most common myopathy after age 50. Prior research is limited to case series and cross-section studies.

Design

A retrospective review of pulmonary function tests, respiratory symptoms, and muscle strength testing.

Results

Of the 54 patients reviewed (mean age: 65 ± 9 years and disease duration: 7 ± 7 years), the majority (n = 32, 59%) had restrictive forced vital capacity (FVC) deficits at initial visit. Patients with reduced FVC showed higher prevalence of respiratory symptoms; but age, body mass index, and limb strength were similar when compared to patients without restrictive FVC. Mean rate of FVC decline of 0.108 L/year in IBM patients. Lower baseline limb strength correlated with longer disease duration and future FVC decline (e.g., weaker patients experienced faster decline).

Conclusion

Based on FVC, there is a high frequency of ventilatory pump muscle weakness in IBM, which is associated with a higher burden of respiratory symptoms. Baseline strength may indicate risk of respiratory decline and need for vigilant screening. Importantly, ventilatory and limb muscle decline may not progress in a corresponding manner, highlighting the importance of pulmonary function surveillance.
Mnemonics and Metaphorical Videos for Detecting/Diagnosing Musculoskeletal Sonopathologies
Authors: Jačisko Jakub , Ricci Vincenzo , Mezian Kamal , Güvener Orhan , Chang Ke-Vin , Kara Murat , Kobesová Alena , Özçakar Levent
Published: October 2022

Musculoskeletal ultrasound identifies a broad range of pathologies. Typical sonographic images of certain pathological/abnormal conditions can be rendered and ‘highlighted‘ for the daily practice/language of musculoskeletal sonographers. The following text and accompanying figures/videos represent a collection of findings pertaining to commonplace pathological conditions. This article is the second part of a series - after the characteristic/metaphoric descriptions of normal musculoskeletal structures.
Evaluating the Potential for ABO-incompatible Islet Transplantation: Expression of ABH Antigens on Human Pancreata, Isolated Islets, and Embryonic Stem Cell-derived Islets
Authors: Verhoeff Kevin , Cuesta-Gomez Nerea , Albers Patrick , Pawlick Rena , Marfil-Garza Braulio A. , Jasra Ila , Dadheech Nidheesh , O’Gorman Doug , Kin Tatsuya , Halpin Anne , West Lori J. , Shapiro A.M. James
Published: October 2022

Background.

ABO-incompatible transplantation has improved accessibility of kidney, heart, and liver transplantation. Pancreatic islet transplantation continues to be ABO-matched, yet ABH antigen expression within isolated human islets or novel human embryonic stem cell (hESC)-derived islets remain uncharacterized.

Methods.

We evaluated ABH glycans within human pancreata, isolated islets, hESC-derived pancreatic progenitors, and the ensuing in vivo mature islets following kidney subcapsular transplantation in rats. Analyses include fluorescence immunohistochemistry and single-cell analysis using flow cytometry.

Results.

Within the pancreas, endocrine and ductal cells do not express ABH antigens. Conversely, pancreatic acinar tissues strongly express these antigens. Acinar tissues are present in a substantial portion of cells within islet preparations obtained for clinical transplantation. The hESC-derived pancreatic progenitors and their ensuing in vivo-matured islet-like clusters do not express ABH antigens.

Conclusions.

Clinical pancreatic islet transplantation should remain ABO-matched because of contaminant acinar tissue within islet preparations that express ABH glycans. Alternatively, hESC-derived pancreatic progenitors and the resulting in vivo-matured hESC-derived islets do not express ABH antigens. These findings introduce the potential for ABO-incompatible cell replacement treatment and offer evidence to support scalability of hESC-derived cell therapies in type 1 diabetes.
Absolute Lymphocyte Count as a Marker for Cytomegalovirus Infection After Heart Transplantation
Authors: Schoeberl Armin-Kai , Zuckermann Andreas , Kaider Alexandra , Aliabadi-Zuckermann Arezu , Uyanik-Uenal Keziban , Laufer Guenther , Goekler Johannes
Published: October 2022

Background.

Previous studies indicate an association between reduced absolute lymphocyte count (ALC) and cytomegalovirus (CMV) infection after solid organ transplantation and have therefore highlighted the potential of ALC as a simple tool to predict CMV infection in transplant patients. This study aimed to examine the utility of ALC as a valuable marker for CMV infection in heart transplant patients.

Methods.

Clinical information and ALC data of all adult patients who received orthotopic heart transplantation at the Medical University of Vienna between January 2004 and May 2019 were collected. We performed a multivariable Cox regression model that incorporates repeated measurements of ALC as a time-varying continuous factor in 2 ways, first as continuous logarithmic factor considering a 50% decrease of ALC levels and second as binary factor using a threshold of 610 cells/μL.

Results.

One hundred fifty-eight (39%) patients developed CMV infection over the course of 2 y. Patients with lymphopenia were shown to be at higher risk of developing CMV infection both in the continuous approach (HR [per 50% reduction] 1.29; confidence interval [CI], 1.09-1.53; P = 0.003) and the binary approach with a cutoff of 610 cells/μL (HR 1.74; CI, 1.20-2.51; P = 0.003).

Conclusions.

This study demonstrated a strong association between reduced ALC and the development of CMV infection after heart transplantation. ALC value monitoring could provide an additional tool to assess individualized CMV risk after solid organ transplantation.
Real-world Evidence of COVID-19 Vaccines Effectiveness in Solid-organ Transplant Recipient Population in Colombia: A Study Nested in the Esperanza Cohort
Authors: Pinto-Álvarez Mariana , Fernández-Niño Julián A. , Arregocés-Castillo Leonardo , Rojas-Botero Maylen L. , Palacios Andrés F. , Galvis-Pedraza Maryory , Ruiz-Gomez Fernando
Published: October 2022

Background.

Solid-organ transplant recipients (SOTRs) have a higher risk of coronavirus disease 2019 (COVID-19) complications and death and a less powerful and lasting response to vaccines and to natural infection. In Colombia, this population was prioritized in the National Vaccination Plan against COVID-19 and received vaccines from different platforms. The aim of this study was to estimate the effectiveness of the complete vaccination schedule and of the vaccine booster for COVID-19 administered to SOTRs in Colombia.

Methods.

A nested-cohort was assembled within the population-based ESPERANZA cohort and included the subset of 16 y and older SOTRs (n = 6963); the follow-up period spanned March 11, 2021, to May 11, 2022. The vaccine effectiveness was estimated with Cox proportional-hazards models so that the overall effectiveness of the complete vaccination schedule, the vaccine booster, each used vaccine, and the homologous and heterologous schedules were estimated, adjusting by the main confounders.

Results.

The overall effectiveness of being fully vaccinated was 73.7% (95% confidence interval [CI], 68.9%-77.0%) to prevent COVID-19 infection, 83.7% (95% CI, 78.7%-87.5%) to prevent hospitalization, and 92.1% (95% CI, 88.8%-94.4%) to prevent death due to COVID-19. Similarly, the effectiveness of the vaccine booster was 76.7% (95% CI, 70.6%-81.5%), 86.9% (95% CI, 79.4%-91.6%), and 94.5% (95% CI, 89.8%-97.1%) to prevent confirmed COVID-19 infection, hospitalization, and death due to COVID-19, respectively. In both cases, there were no statistically significant differences across age groups.

Conclusions.

Findings from this work show a high protection of vaccination against infection, hospitalization, and death due to COVID-19 in SOTRs, which increases with the vaccine booster.
Spasticity following brain and spinal cord injury: assessment and treatment
Authors: Tamburin Stefano , Filippetti Mirko , Mantovani Elisa , Smania Nicola , Picelli Alessandro
Published: October 2022

Purpose of review

Spasticity is a common sequela of brain and spinal cord injury and contributes to disability, reduces quality of life, and increases economic burden. Spasticity is still incompletely recognized and undertreated. We will provide an overview of recent published data on the definition, assessment, and prediction, therapeutic advances, with a focus on promising new approaches, and telemedicine applications for spasticity.

Recent findings

Two new definitions of spasticity have been recently proposed, but operational criteria should be developed, and test–retest and inter-rater reliability should be explored. Cannabinoids proved to be effective in spasticity in multiple sclerosis, but evidence in other types of spasticity is lacking. Botulinum neurotoxin injection is the first-line therapy for focal spasticity, and recent literature focused on optimizing its efficacy. Several pharmacological, interventional, and nonpharmacological therapeutic approaches for spasticity have been explored but low-quality evidence impedes solid conclusions on their efficacy. The recent COVID-19 pandemic yielded guidelines/recommendations for the use of telemedicine in spasticity.

Despite the frequency of spasticity, robust diagnostic criteria and reliable assessment scales are required. High-quality studies are needed to support the efficacy of current treatments for spasticity. Future studies should explore telemedicine tools for spasticity assessment and treatment.
Assessment and treatment of neurogenic dysphagia in stroke and Parkinson's disease
Authors: Cosentino Giuseppe , Todisco Massimiliano , Giudice Carla , Tassorelli Cristina , Alfonsi Enrico
Published: October 2022

Purpose of review

Neurogenic dysphagia worsens quality of life and prognosis of patients with different neurological disorders. Management of neurogenic dysphagia can be challenging. This review provides a comprehensive overview of current evidence on screening, diagnosis, and treatment of neurogenic dysphagia in stroke and Parkinson's disease, suggesting clues for clinical practice.

Recent findings

The pros and cons of diagnostic techniques are discussed in the light of updated evidence. Findings from recent meta-analyses of different treatment approaches, including traditional dysphagia therapy, peripheral and central neurostimulation techniques, and treatment with botulinum toxin, are critically discussed, emphasizing inconsistencies and controversial issues.

Screening tests and clinical swallow examination should be routinely performed in neurological patients at risk for dysphagia. In patients testing positive for dysphagia, first-line instrumental investigations, represented by fiberoptic endoscopic evaluation of swallowing or videofluoroscopic swallow study, should be performed to confirm the presence of dysphagia, to assess its severity, and to inform the treatment. Second-line and third-line instrumental methods can be used in selected patients to clarify specific pathophysiological aspects of oropharyngeal dysphagia. Treatment strategies should be personalized, and combination of traditional dysphagia therapy with innovative treatment approaches may increase the chance of restoring effective and safe swallowing.
Mucus from human bronchial epithelial cultures: rheology and adhesion across length scales
Authors: Jory Myriam , Donnarumma Dario , Blanc Christophe , Bellouma Karim , Fort Aurélie , Vachier Isabelle , Casanellas Laura , Bourdin Arnaud , Massiera Gladys
Published: October 2022

Mucus is a viscoelastic aqueous fluid that participates in the protective barrier of many mammals' epithelia. In the airways, together with cilia beating, mucus rheological properties are crucial for lung mucociliary function, and, when impaired, potentially participate in the onset and progression of chronic obstructive pulmonary disease (COPD). Samples of human mucus collected
in vivo
are inherently contaminated and are thus poorly characterized. Human bronchial epithelium (HBE) cultures, differentiated from primary cells at an air–liquid interface, are highly reliable models to assess non-contaminated mucus. In this paper, the viscoelastic properties of HBE mucus derived from healthy subjects, patients with COPD and from smokers are measured. Hallmarks of shear-thinning and elasticity are obtained at the macroscale, whereas at the microscale mucus appears as a heterogeneous medium showing an almost Newtonian behaviour in some extended regions and an elastic behaviour close to boundaries. In addition, we developed an original method to probe mucus adhesion at the microscopic scale using optical tweezers. The measured adhesion forces and the comparison with mucus-simulants rheology as well as mucus imaging collectively support a structure composed of a network of elastic adhesive filaments with a large mesh size, embedded in a very soft gel.
Experimental challenges in determining the rheological properties of bacterial biofilms
Authors: Geisel Steffen , Secchi Eleonora , Vermant Jan
Published: October 2022

Bacterial biofilms are communities living in a matrix consisting of self-produced, hydrated extracellular polymeric substances. Most microorganisms adopt the biofilm lifestyle since it protects by conferring resistance to antibiotics and physico-chemical stress factors. Consequently, mechanical removal is often necessary but rendered difficult by the biofilm’s complex, viscoelastic response, and adhesive properties. Overall, the mechanical behaviour of biofilms also plays a role in the spreading, dispersal and subsequent colonization of new surfaces. Therefore, the characterization of the mechanical properties of biofilms plays a crucial role in controlling and combating biofilms in industrial and medical environments. We performed
in situ
shear rheological measurements of
Bacillus subtilis
biofilms grown between the plates of a rotational rheometer under well-controlled conditions relevant to many biofilm habitats. We investigated how the mechanical history preceding rheological measurements influenced biofilm mechanics and compared these results to the techniques commonly used in the literature. We also compare our results to measurements using interfacial rheology on bacterial pellicles formed at the air–water interface. This work aims to help understand how different growth and measurement conditions contribute to the large variability of mechanical properties reported in the literature and provide a new tool for the rigorous characterization of matrix components and biofilms.
Flow simulations of rectal evacuation: towards a quantitative evaluation from video defaecography
Authors: Ahmad Faisal , Tanguy Stéphane , Dubreuil Alain , Magnin Albert , Faucheron Jean-Luc , de Loubens Clément
Published: October 2022

Mechanistic understanding of anorectal (patho)physiology is missing to improve the medical care of patients suffering from defaecation disorders. Our objective is to show that complex fluid dynamics modelling of video defaecography may open new perspectives in the diagnosis of defaecation disorders. Based on standard X-ray video defaecographies, we developed a bi-dimensional patient-specific simulation of the expulsion of soft materials, the faeces, by the rectum. The model quantified velocity, pressure and stress fields during the defaecation of a neostool with soft stool-like rheology for patients showing normal and pathological defaecatory function. In normal defaecation, the proximal–distal pressure gradient resulted from both the anorectal junction which formed a converging channel and the anal canal. The flow of the neostool through these anatomical parts was dominated by its shear-thinning viscous properties, rather than its yield stress. Consequently, the evacuation flow rate was significantly affected by variations in pressure applied by the rectum, and much less by the geometry of the anorectal junction. Lastly, we simulated impaired defaecations in the absence of obvious obstructive phenomena. Comparison with normal defaecation allowed us to discuss critical elements which should lead to effective medical management.
How dynamic prestress governs the shape of living systems, from the subcellular to tissue scale
Authors: Erlich Alexander , Étienne Jocelyn , Fouchard Jonathan , Wyatt Tom
Published: October 2022

Cells and tissues change shape both to carry out their function and during pathology. In most cases, these deformations are driven from within the systems themselves. This is permitted by a range of molecular actors, such as active crosslinkers and ion pumps, whose activity is biologically controlled in space and time. The resulting stresses are propagated within complex and dynamical architectures like networks or cell aggregates. From a mechanical point of view, these effects can be seen as the generation of prestress or prestrain, resulting from either a contractile or growth activity. In this review, we present this concept of prestress and the theoretical tools available to conceptualize the statics and dynamics of living systems. We then describe a range of phenomena where prestress controls shape changes in biopolymer networks (especially the actomyosin cytoskeleton and fibrous tissues) and cellularized tissues. Despite the diversity of scale and organization, we demonstrate that these phenomena stem from a limited number of spatial distributions of prestress, which can be categorized as heterogeneous, anisotropic or differential. We suggest that in addition to growth and contraction, a third type of prestress—topological prestress—can result from active processes altering the microstructure of tissue.
Correlating viscosity and molecular crowding with fluorescent nanobeads and molecular probes:
in vitro
and
in vivo
Authors: Lecinski Sarah , Shepherd Jack W. , Bunting Kate , Dresser Lara , Quinn Steven D. , MacDonald Chris , Leake Mark C.
Published: October 2022

In eukaryotes, intracellular physico-chemical properties like macromolecular crowding and cytoplasmic viscoelasticity influence key processes such as metabolic activities, molecular diffusion and protein folding. However, mapping crowding and viscoelasticity in living cells remains challenging. One approach uses passive rheology in which diffusion of exogenous fluorescent particles internalized in cells is tracked and physico-chemical properties inferred from derived mean square displacement relations. Recently, the crGE2.3 Förster resonance energy transfer biosensor was developed to quantify crowding in cells, though it is unclear how this readout depends on viscoelasticity and the molecular weight of the crowder. Here, we present correlative, multi-dimensional data to explore diffusion and molecular crowding characteristics of molecular crowding agents using super-resolved fluorescence microscopy and ensemble time-resolved spectroscopy. We firstly characterize
in vitro
and then apply these insights to live cells of budding yeast
Saccharomyces cerevisiae
. It is to our knowledge the first time this has been attempted. We demonstrate that these are usable both
in vitro
and in the case of endogenously expressed sensors in live cells. Finally, we present a method to internalize fluorescent beads as
in situ
viscoelasticity markers in the cytoplasm of live yeast cells and discuss limitations of this approach including impairment of cellular function.
High titers of infectious SARS-CoV-2 in COVID-19 corpses
Authors: Saitoh Hisako , Sakai-Tagawa Yuko , Nagasawa Sayaka , Torimitsu Suguru , Kubota Kazumi , Hirata Yuichiro , Iwatsuki-Horimoto Kiyoko , Motomura Ayumi , Ishii Namiko , Okaba Keisuke , Horioka Kie , Abe Hiroyuki , Ikemura Masako , Rokutan Hirofumi , Hinata Munetoshi , Iwasaki Akiko , Yasunaga Yoichi , Nakajima Makoto , Yamaguchi Rutsuko , Tsuneya Shigeki , Kira Kei , Kobayashi Susumu , Inokuchi Go , Chiba Fumiko , Hoshioka Yumi , Mori Aika , Yamamoto Isao , Nakagawa Kimiko , Katano Harutaka , Iida Shun , Suzuki Tadaki , Akitomi Shinji , Hasegawa Iwao , Ushiku Tetsuo , Yajima Daisuke , Iwase Hirotaro , Makino Yohsuke , Kawaoka Yoshihiro
Published: October 2022

Background

The prolonged presence of infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) in deceased coronavirus disease 2019 (COVID-19) patients has been reported. However, infectious virus titers have not been determined. Such information is important for public health, death investigation, and handling corpses.

Aim

The aim of this study was to assess the level of SARS-CoV-2 infectivity in COVID-19 corpses.

Methods

We collected 11 nasopharyngeal swabs and 19 lung tissue specimens from 11 autopsy cases with COVID-19 in 2021. We then investigated the viral genomic copy number by real-time reverse transcription-polymerase chain reaction and infectious titers by cell culture and virus isolation.

Results

Infectious virus was present in 6 of 11 (55%) cases, 4 of 11 (36%) nasopharyngeal swabs, and 9 of 19 (47%) lung specimens. The virus titers ranged from 6.00E + 01 plaque-forming units (PFU)/mL to 2.09E + 06 PFU/g. In all cases in which an infectious virus was found, the time from death to discovery was within 1 day and the longest postmortem interval was 13 days.

Conclusion

COVID-19 corpses may have high titers of infectious virus after a long postmortem interval (up to 13 days). Therefore, appropriate infection control measures must be taken when handling corpses.
HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia
Authors: Singh Shuchi Agrawal , Bagri Jaana , Giotopoulos George , Azazi Dhoyazan , Anand Shubha , Bach Anne-Sophie , Stedham Frances , Horton Sarah J. , Antrobus Robin , Houghton Jack W. , Vassiliou George S. , Sasca Daniel , Yun Haiyang , Whetton Anthony D. , Huntly Brian J.P.
Published: October 2022

HOXA9is commonly upregulated in acute myeloid leukemia (AML), where it confers poor prognosis. Characterising the protein interactome of endogenous HOXA9 in human AML, we identified a chromatin complex of HOXA9 with the nuclear matrix attachment protein-SAFB.SAFBperturbation phenocopiedHOXA9knockout to decrease AML proliferation, increase differentiation and apoptosisin vitroand prolonged survivalin vivo. Integrated genomic, transcriptomic and proteomic analyses further demonstrated that the HOXA9-SAFB-chromatin complex associates with NuRD and HP1γ to repress the expression of factors associated with differentiation and apoptosis, includingNOTCH, CEBPδ,S100A8, andCDKN1A. Chemical or genetic perturbation of NuRD and HP1γ catalytic activity also triggered differentiation, apoptosis and the induction of these tumor-suppressive genes. Importantly, this mechanism is operative in other HOXA9-dependent AML genotypes. This mechanistic insight demonstrates activeHOXA9-dependent differentiation block as a potent mechanism of disease maintenance in AML, that may be amenable to therapeutic intervention via therapies targeting the HOXA9/SAFB interface and/or NuRD and HP1γ activity.

Key Points

-

Identification of the endogenous human HOXA9 protein interactome in AML

-

HOXA9 forms a repressive complex with S/MAR binding protein (SAFB) that is critical for the maintenance of AML by facilitating proliferation and preventing differentiation and cell death.

-

The HOXA9/SAFB (H9SB) complex represses gene expression via recruitment of NuRD and HP1γ.
Being socially present in a time of social distancing: investigating the online social learning experiences of teacher-trainees during COVID-19
Authors: Almahdi Maryam Husain , Al Murshidi Ghadah , Al-Mahdi Osama
Published: October 2022

Purpose

This paper investigates the social online learning experiences of teacher trainees during the COVID-19 pandemic. The study's model gauges the relationships between social presence, sense of community, and collaborative learning in online work-based learning environments.

Design/methodology/approach

This study uses a cross-sectional design, specifically an online questionnaire, to collect data from teacher-trainees in different years of their university programs.

Findings

The findings indicate significant and positive relationships between social presence and both sense of community and collaborative learning, and between collaborative learning and sense of community in a work-based online learning environment. Moreover, collaborative learning was found to mediate the relationship between social presence and sense of community in the study's model.

Research limitations/implications

The use of questionnaires to collect self-reported data from a mostly female undergraduate sample is expected to affect the generalizability of the results. Experiments or observation methods and a wider sample of participants can be used in future research to build on the findings of this study.

Practical implications

The authors recommend that educators play an active role in improving the students' online social learning experiences, especially their social presence and collaborative learning. By using different interactive methods (e.g. encouraging students to ask questions, express emotions, share resources, and reflect on their learning in a group), educators can help students achieve a sense of community and, hence, realize the many beneficial outcomes tied to community creation in online learning environments.

Originality/value

The study contributes to knowledge by highlighting students' social experiences while learning online, a usually overlooked area of study. These insights are especially important in a time when online learning has become a necessity rather than a choice and when students are in dire need of social support and community. Researching the online social learning experiences of teacher-trainees lends additional value to the study, as it is necessary for future teachers to experience and master this type of learning during their pre-service training so they can apply it with higher levels of confidence and efficacy in their future classrooms.