bluuebunny/crossref_metadata_2025 huggingface dataset:
A Real-World Evaluation of a Smokeless Tobacco Cessation Text Message Program for Veterans: Outcomes and Comparison to Cigarette Smokers
Authors: Christofferson Dana E , Blalock Dan V , Knoeppel Jennifer , Beckham Jean C , Hamlett-Berry Kim , Hertzberg Jeffrey S
Published: September 2021

Introduction

Smokeless tobacco (ST) use and cessation rates have remained unchanged while cigarette smoking has declined, and cessation rates have increased. Text message programs have proved effective for cigarette smokers but have not been evaluated for ST users. The Veterans Health Administration (VHA) created a ST-specific arm of its SmokefreeVET automated text message program to help veteran ST users quit.

Aims and Methods

A retrospective evaluation was conducted on a real-world sample of veteran ST users (n = 1139) who subscribed to SmokefreeVET between 2017 and 2020. Time in program, abstinence, and nicotine replacement therapy (NRT) use were evaluated and compared to 9764 cigarette smokers who subscribed to SmokefreeVET.

Results

Younger subscribers were more likely to opt out early; 54% of ST users and 60% of cigarette smokers completed the 6-week program. ST users were more likely to report abstinence than cigarette smokers at all time points: the primary outcome, 30-day abstinence at 6 months, was 3.9% in ST users and 2.6% in cigarette smokers (p = .05) and the secondary outcome, abstinence at 3 months, was 5.3% in ST users and 3.4% in cigarette smokers (p = .03). NRT was used by 17% of ST users and was associated with a trend toward higher abstinence compared to ST users who did not use NRT.

Conclusion

A real-world sample of ST users were more likely to report abstinence after using the SmokefreeVET text program than cigarette smokers. Automated text message programs may be effective for increasing cessation among ST users and warrant further investigation.

Implications

Smokeless tobacco (ST) cessation is an important public health priority and of importance for veteran and military populations that have higher rates of ST use. There have been relatively few studies conducted investigating the effectiveness of text message interventions for ST cessation, despite the proven efficacy for cigarette smokers. This study provides evidence from a large, real-world sample that text message programs may be effective for ST users and suggests that further research into this treatment modality for ST users is needed.
GIGANTEA influences leaf senescence in trees in two different ways
Authors: Fataftah Nazeer , Bag Pushan , André Domenique , Lihavainen Jenna , Zhang Bo , Ingvarsson Pär K , Nilsson Ove , Jansson Stefan
Published: September 2021

GIGANTEA (GI) genes have a central role in plant development and influence several processes. Hybrid aspen T89 (Populus tremula x tremuloides) trees with low GI expression engineered through RNAi show severely compromised growth. To study the effect of reduced GI expression on leaf traits with special emphasis on leaf senescence, we grafted GI-RNAi scions onto wild-type rootstocks and successfully restored growth of the scions. The RNAi line had a distorted leaf shape and reduced photosynthesis, probably caused by modulation of phloem or stomatal function, increased starch accumulation, a higher carbon-to-nitrogen ratio, and reduced capacity to withstand moderate light stress. GI-RNAi also induced senescence under long day (LD) and moderate light conditions. Furthermore, the GI-RNAi lines were affected in their capacity to respond to “autumn environmental cues” inducing senescence, a type of leaf senescence that has physiological and biochemical characteristics that differ from those of senescence induced directly by stress under LD conditions. Overexpression of GI delayed senescence under simulated autumn conditions. The two different effects on leaf senescence under LD or simulated autumn conditions were not affected by the expression of FLOWERING LOCUS T. GI expression regulated leaf senescence locally—the phenotype followed the genotype of the branch, independent of its position on the tree—and trees with modified gene expression were affected in a similar way when grown in the field as under controlled conditions. Taken together, GI plays a central role in sensing environmental changes during autumn and determining the appropriate timing for leaf senescence in Populus.
Mobilizing Knowledge in Frontline Work: A Conceptual Framework and Empirical Exploration
Authors: Møller Anne Mette
Published: September 2021

Frontline workers bring different forms of knowledge to bear on decisions and actions. Even so, knowledge has so far received limited attention in the street-level literature. This article develops a nuanced understanding of what constitutes knowledge in frontline work and shows how different forms of knowledge are mobilized on the ground. Taking a practice-based and abductive approach, the article draws on qualitative data from a multi-sited organizational ethnography in three Danish child welfare agencies as well as insights from a broad range of literature to build a conceptual framework for studying knowledge mobilization in frontline work. The framework delineates three interdependent forms of knowledge—knowledge-that, knowledge-how, and knowledge-by-acquaintance—that are all essential in frontline work. Knowledge-that is explicit and includes research evidence. Knowledge-how is rooted in experience and acquired through practice. Knowledge-by-acquaintance is rooted in encounters and denotes frontline workers’ “sense” of a case or situation. The empirical work shows how each form of knowledge is mobilized in practice. The findings yield important insights into the dynamics of knowledge mobilization at the frontlines, including the detrimental effects of rapid turnover, the conditions for realizing ideals such as evidence-based practice and data-driven decision-making, and the potential implications of digitalization and algorithmization.
Standardization of inducer-activated broad host range expression modules: debugging and refactoring an alkane-responsive AlkS/PalkB device
Authors: Arce-Rodríguez Alejandro , Benedetti Ilaria , Borrero-de Acuña José Manuel , Silva-Rocha Rafael , de Lorenzo Víctor
Published: September 2021

Although inducible heterologous expression systems have been available since the birth of recombinant DNA technology, the diversity of genetic devices and their coming together in the corresponding vectors often result in a lack of reproducibility and interoperability. In an effort to increase the predictability of expression of genes of interest in a variety of possible bacterial hosts, we propose a composition standard for debugging and reassembling all regulatory parts that participate in the performance of such devices. As a case study, we addressed the n-octane and dicyclopropyl ketone-inducible PalkB promoter of the alkane biodegradation pOCT plasmid of Pseudomonas putida. The standardized expression module included an edited alkS transcription factor divergently expressed and separated from PalkB by a synthetic buffer segment. The DNA sequence of the alkS gene was modified to alleviate the catabolite repression exerted by several carbon and nitrogen sources through the Crc/Hfq complex of some hosts. The PalkB promoter and the alkS variants were then formatted as Standard European Vector Architecture cargoes, and their activity in P. putida was quantified with fluorescent and luminescent reporters. Despite considerable editing of the DNA sequences involved, the thereby refactored module basically kept the functioning parameters of the original configuration. The same qualities were inspected when the system was passed to Escherichia coli and Pseudomonas aeruginosa. We argue that the application of the compositional standard thereby implemented in the AlkS/PalkB module to other promoter/regulator pairs will enable more complex genetic programming in non-model bacteria.
Vestibular Perceptual Thresholds in Older Adults With and Without Age-related Hearing Loss
Authors: Gabriel Grace A. , Harris Laurence R. , Gnanasegaram Joshua J. , Cushing Sharon L. , Gordon Karen A. , Haycock Bruce C. , Pichora-Fuller M. Kathleen , Campos Jennifer L.
Published: September 2021

Objectives:

Older adults with age-related hearing loss (ARHL) are at greater risk of falling and have greater mobility problems than older adults with normal hearing (NH). The underlying cause of these associations remains unclear. One possible reason is that age-related declines in the vestibular system could parallel those observed in the auditory system within the same individuals. Here, we compare the sensitivity of vestibular perceptual abilities (psychophysics), vestibular end-organ functioning (vestibular evoked myogenic potentials and video head impulse tests), and standing balance (posturography) in healthy older adults with and without ARHL.

Design:

A total of 46 community-dwelling older adults, 23 with ARHL and 23 with NH, were passively translated in heave (up and down) and rotated in pitch (tilted forward and backward) in the dark using a motion platform. Using an adaptive staircase psychophysical procedure, participants’ heave and pitch detection and discrimination thresholds were determined. In a posturography task, participants’ center of pressure (COP) path length was measured as they stood on a forceplate with eyes open and closed, on firm and compliant surfaces, with and without sound suppression. Baseline motor, cognitive, and sensory functioning, including vestibular end-organ function, were measured.

Results:

Individuals with ARHL were less sensitive at discriminating pitch movements compared to older adults with NH. Poorer self-reported hearing abilities were also associated with poorer pitch discrimination. In addition to pitch discrimination thresholds, lower pitch detection thresholds were significantly associated with hearing loss in the low-frequency range. Less stable standing balance was significantly associated with poorer vestibular perceptual sensitivity.

Discussion:

These findings provide evidence for an association between ARHL and reduced vestibular perceptual sensitivity.
Increase in Osteoporotic U-Type Sacral Fractures: Role of the Transiliac-Transsacral Screw Versus Lumbopelvic Fixation
Authors: Wright Raymond D. , Cassidy R. Carter , Kark Jonathan
Published: September 2021

As the population is increasing in age, so increases the number of osteoporotic fractures. U-shaped sacral fractures can be difficult to diagnose and may be a source of disability in patients when left untreated. Many patients with osteoporotic fractures are of advanced age and may experience rapid medical decline when these fractures cause immobility. We present surgical options for U-shaped sacral fracture management.
Effect of a Multicomponent Sepsis Transition and Recovery Program on Mortality and Readmissions After Sepsis: The Improving Morbidity During Post-Acute Care Transitions for Sepsis Randomized Clinical Trial*
Authors: Taylor Stephanie Parks , Murphy Stephanie , Rios Aleta , McWilliams Andrew , McCurdy Lewis , Chou Shih-Hsiung , Hetherington Timothy , Rossman Whitney , Russo Mark , Gibbs Michael , Kowalkowski Marc A.
Published: September 2021

OBJECTIVES:

To evaluate whether a nurse navigator-led, multicomponent Sepsis Transition And Recovery program improves 30-day mortality and readmission outcomes after sepsis hospitalization.

Desig

n: Multisite pragmatic randomized clinical trial.

SETTING:

Three hospitals in North Carolina from January 2019 to March 2020.

PATIENTS:

Eligible patients hospitalized for suspected sepsis and deemed high-risk for mortality or readmission by validated internal risk models.

INTERVENTIONS:

Patients were randomized to receive usual care alone (i.e., routine transition support, outpatient care; n = 342) or additional Sepsis Transition And Recovery support (n = 349). The 30-day intervention involved a multicomponent transition service led by a nurse navigator through telephone and electronic health record communication to facilitate best practice postsepsis care strategies during and after hospitalization including: postdischarge medication review, evaluation for new impairments or symptoms, monitoring comorbidities, and palliative care approach when appropriate. Clinical oversight was provided by a Hospital Medicine Transition Services team.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was a composite of mortality or hospital readmission at 30 days. Logistic regression models were constructed to evaluate marginal and conditional odds ratios (adjusted for prognostic covariates: age, comorbidity, and organ dysfunction at enrollment). Among 691 randomized patients (mean age = 63.7 ± 15.1 yr; 52% female), a lower percentage of patients in the Sepsis Transition And Recovery group experienced the primary outcome compared with the usual care group (28.7% vs 33.3%; risk difference, 4.7%; odds ratio, 0.80; 95% CI, 0.58–1.11; adjusted odds ratio, 0.80; 95% CI, 0.64–0.98). There were 74 deaths (Sepsis Transition And Recovery: 33 [9.5%] vs usual care: 41 [12.0%]) and 155 rehospitalizations (Sepsis Transition And Recovery: 71 [20.3%] vs usual care: 84 [24.6%]).

CONCLUSIONS:

In a multisite randomized clinical trial of patients hospitalized with sepsis, patients provided with a 30-day program using a nurse navigator to provide best practices for postsepsis care experienced a lower proportion of either mortality or rehospitalization within 30 days after discharge. Further research is needed to understand the contextual factors associated with successful implementation.
A retrospective clinical study of patients with pregnancy-associated breast cancer among multiple centers in China (CSBrS-008)
Authors: Jin Yu-Chun , Du Jun-Xian , Fu Shao-Mei , Chen Qin , Qiu Yi-Ran , Pei An , Yao Yi-Jing , Zhu Wei , Wu Ke-Jin
Published: September 2021

Background:

Pregnancy-associated breast cancer (PABC) is a special type of breast cancer that occurs during pregnancy and within 1 year after childbirth. With the rapid social development and the adjustment of reproductive policies in China, the average age of females at first childbirth is increasing, which is expected to lead to an increase in the incidence of PABC. This study aimed to accumulate clinical experience and to investigate and summarize the prevalence, diagnosis, and treatment of PABC based on large multicenter samples in China.

Methods:

According to the Chinese Society of Breast Surgery, a total of 164 patients with PABC in 27 hospitals from January 2016 to December 2018 were identified. The pregnancy status, clinicopathological features, comprehensive treatment methods, and outcomes were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method.

Results:

A total of 164 patients of PABC accounted for 0.30% of the total number of cases in the same period; of which, 83 patients were diagnosed during pregnancy and 81 patients during lactation. The median age of PABC was 33 years (24–47 years). Stage I patients accounted for 9.1% (15/164), stage II 54.9% (90/164), stage III 24.4% (40/164), and stage IV 2.4% (4/164). About 9.1% (15/164) of patients were luminal A. Luminal B patients accounted the most (43.3% [71/164]). About 15.2% (25/164) of patients were human epidermal growth factor receptor 2 (Her-2) overexpression and 18.9% (31/164) of patients were triple-negative breast cancer. For pregnancy breast cancer, 36.1% (30/83) of patients received direct surgery and 20.5% (17/83) received chemotherapy during pregnancy. About 31.3% (26/83) chose abortion or induction of labor. The median follow-up time was 36 months (3–59 months); 11.0% (18/164) patients had local recurrence or distant metastasis and 3.0% (5/164) died.

Conclusions:

It is safe and feasible to standardize surgery and chemotherapy for PABC.
Clinical risk score for postoperative pneumonia following heart valve surgery
Authors: Wang Da-Shuai , Huang Xiao-Fan , Wang Hong-Fei , Le Sheng , Du Xin-Ling
Published: September 2021

Background:

Postoperative pneumonia (POP) is one of the most common infections following heart valve surgery (HVS) and is associated with a significant increase in morbidity, mortality, and health care costs. This study aimed to identify the major risk factors associated with the occurrence of POP following HVS and to derive and validate a clinical risk score.

Methods:

Adults undergoing open HVS between January 2016 and December 2019 at a single institution were enrolled in this study. Patients were randomly assigned to the derivation and validation sets at 1:1 ratio. A prediction model was developed with multivariable logistic regression analysis in the derivation set. Points were assigned to independent risk factors based on their regression coefficients.

Results:

POP occurred in 316 of the 3853 patients (8.2%). Multivariable analysis identified ten significant predictors for POP in the derivation set, including older age, smoking history, chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, poor cardiac function, heart surgery history, longer cardiopulmonary bypass, blood transfusion, and concomitant coronary and/or aortic surgery. A 22-point risk score based on the multivariable model was then generated, demonstrating good discrimination (C-statistic: 0.81), and calibration (Hosmer-Lemeshow χ
2 = 8.234, P = 0.312). The prediction rule also showed adequate discriminative power (C-statistic: 0.83) and calibration (Hosmer-Lemeshow χ
2 = 5.606, P = 0.691) in the validation set. Three risk intervals were defined as low-, medium-, and high-risk groups.

Conclusion:

We derived and validated a 22-point risk score for POP following HVS, which may be useful in preventive interventions and risk management.

Trial Registration:

Chictr.org, ChiCTR1900028127; http://www.chictr.org.cn/showproj.aspx?proj=46932
Biomechanical evaluation of a novel transtibial posterior cruciate ligament reconstruction using high-strength sutures in a porcine bone model
Authors: Duan Ming-Yi , Sun Rui , Zhuang Lei-Ting , Zhang Hang-Zhou
Published: September 2021

Background:

Multiple techniques are commonly used for posterior cruciate ligament (PCL) reconstruction. However, the optimum method regarding the fixation of PCL reconstruction after PCL tears remains debatable. The purpose of this study was to compare the biomechanical properties among three different tibial fixation procedures for transtibial single-bundle PCL reconstruction.

Methods:

Thirty-six porcine tibias and porcine extensor tendons were randomized into three fixation study groups: the interference screw fixation (IS) group, the transtibial tubercle fixation (TTF) group, and TTF + IS group (n = 12 in each group). The structural properties of the three fixation groups were tested under cyclic loading and load-to-failure. The slippage after the cyclic loading test and the stiffness and ultimate failure load after load-to-failure testing were recorded.

Results:

After 1000 cycles of cyclic testing, no significant difference was observed in graft slippage among the three groups. For load-to-failure testing, the TTF + IS group showed a higher ultimate failure load than the TTF group and the IS group (876.34 ± 58.78 N vs. 660.92 ± 77.74 N [P < 0.001] vs. 556.49 ± 65.33 N [P < 0.001]). The stiffness in the TTF group was significantly lower than that in the IS group and the TTF + IS group (92.77 ± 20.16 N/mm in the TTF group vs. 120.27 ± 15.66 N/m in the IS group [P = 0.001] and 131.79 ± 17.95 N/mm in the TTF + IS group [P < 0.001]). No significant difference in the mean stiffness was found between the IS group and the TTF + IS group (P = 0.127).

Conclusions:

In this biomechanical study, supplementary fixation with transtibial tubercle sutures increased the ultimate failure load during load-to-failure testing for PCL reconstruction.
A rare case report of anal canal adenocarcinoma
Authors: Song Xiaowei , Zhao Huimin , Yang Yongping , Zhao Linxian , Zhao Yongqing , Li Jiannan
Published: September 2021

Rationale:

Anal canal adenocarcinoma is a kind of rare malignant tumor of the intestinal tract with a low incidence rate.

Patient concerns:

A 42-year-old man came to our department with anal tenderness accompanied by intermittent drainage of mucus discharge for 2 weeks.

Diagnoses:

The computer tomography showed a strip-shaped high-density shadow in the rectal wall. The magnetic resonance imaging showed a cyst-like mass of about 33 × 57 × 30 mm in the anal area. The lesion penetrated the anal canal, and plaque-shaped high signal shadow can be seen in the left side of the anus. The intraoperative pathology indicated the mass as anal canal adenocarcinoma.

Interventions:

The abdominal perineal resection was performed for this patient. The postsurgical pathology showed that the tumor was anal canal adenocarcinoma with large amounts of mucus.

Outcomes:

The patient recovered well and was discharged from our department at 12th day post-surgery. This patient received further pelvic radiotherapy.

Lessons:

Anal canal adenocarcinoma is a kind of malignant tumor that is extremely rare clinically. Computer tomography, magnetic resonance imaging, coloscopy, and histopathology are vital for the diagnosis of anal canal adenocarcinoma. Comprehensive treatment, including abdominal perineal resection, radiotherapy, and chemotherapy, is important for the treatment of anal canal adenocarcinoma.
Retroperitoneoscopic debridement and internal fixation for the treatment of lumbar tuberculosis
Authors: Tang Yong , Ye Jichao , Hu Xumin , Yang Wei
Published: September 2021

To describe the retroperitoneoscopic debridement technique and evaluate the clinical outcome of internal fixation for the treatment of lumbar tuberculosis.

Twenty-eight patients were performed conventional laparoendoscopic technique (n = 17) or laparoendoscopic single-site technique (n = 11). Antituberculosis chemotherapy and thoracolumbosacral orthosis were given to all patients. The clinical outcomes were evaluated with preoperative and postoperative Visual Analog Scale, and radiographs with respect to sagittal angle and fusion status.

Average time of the 28 procedures was 220.6 ± 50.9 min (180–365 min). The average intraoperative blood loss was 108.6 ± 95.3 mL (50–400 mL). All patients showed significant improvement of their Visual Analog Scale back pain score at follow-up and were classified as having a radiographic fusion in this study. The mean sagittal angle was 11.2 ± 3.6° before operation, significantly improved to 3.7 ± 2.4° after operation. There were no recurrent infections during the follow-up period. Complications included loosening of anterior fixation and temporary deficit of the sympathetic nerve.

Retroperitoneal laparoscopic approach with CO2 insufflation technique is a challenging but safe and effective procedure for lumbar spine tuberculosis. Retroperitoneal laparoendoscopic single-site can be used for anterior lumbar spine surgery, offer exposure for L1 through L5.
Detecting and preventing post-hematopoietic cell transplant relapse in AML
Authors: Austin Anne E. , Byrne Michael
Published: September 2021

Purpose of review

Relapsed disease is the primary cause of mortality for acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (HCT). This review outlines the most recent advances in the detection and prevention of AML relapse following allogeneic HCT.

Recent findings

Conventional methods for predicting post-HCT relapse rely on the molecular and cytogenetics features present at diagnosis. These methods are slow to reflect a growing understanding of the molecular heterogeneity of AML and impact of new therapies on post-HCT outcomes. The use of measurable residual disease (MRD) techniques, including multiparameter flow cytometry and molecular testing, may improve the prognostic ability of these models and should be incorporated into post-HCT surveillance whenever possible.

In the post-HCT setting, FLT3 inhibitor maintenance data indicate that effective therapies can improve post-HCT outcomes. Maintenance data with DNA methyltransferase inhibitor monotherapy is less compelling and outcomes may improve with combinations. Early interventions directed at preemptive management of MRD may further improve post-HCT outcomes.

Post-HCT AML relapse prevention has evolved to include more sensitive measures of disease detection and novel therapies that may improve outcomes of poor-risk AML patients. Additional work is needed to maintain this progress.
Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children
Authors: Schulert Grant S. , Blum Sydney A. , Cron Randy Q.
Published: September 2021

Purpose of review

This review is meant to describe the genetic associations with pediatric severe COVID-19 pneumonia and the postinfectious complication of the multisystem inflammatory syndrome in children (MIS-C). Multiple genetic approaches have been carried out, primarily in adults with extrapolation to children, including genome-wide association studies (GWAS), whole exome and whole genome sequencing (WES/WGS), and target gene analyses.

Recent findings

Data from adults with severe COVID-19 have identified genomic regions (human leukocyte antigen locus and 3p21.31) as potential risk factors. Genes related to viral entry into cells (ABO blood group locus, ACE2, TMPRS22) have been linked to severe COVID-19 patients by GWAS and target gene approaches. Type I interferon (e.g. IFNAR2) and antiviral gene (e.g. TLR7) associations have been identified by several genetic approaches in severe COVID-19. WES has noted associations with several immune regulatory genes (e.g. SOCS1). Target gene approaches have identified mutations in perforin-mediated cytolytic pathway genes in children and adults with severe COVID-19 and children with MIS-C.

Several genetic associations have been identified in individuals with severe COVID-19 and MIS-C via various genetic approaches. Broadly speaking, COVID-19 genetic associations include genes involved with antiviral functions, viral cell entry, immune regulation, chemotaxis of white blood cells, and lymphocyte cytolytic function.
Detecting Green Fluorescent Protein-tagged Cryptococcus neoformans by Immunofluorescence on Paraffin-embedded Brain Sections
Authors: Wenbiao Chen , Yingcai Zhong , Longkun Zhu
Published: September 2021

Cryptococcus neoformans is an important pathogen causing opportunistic fungal meningitis. The pathogenic mechanism of cryptococcal meningitis remains unclear. We aimed to describe a practical approach for studying the pathologic features of cryptococcal central nervous system infection by immunofluorescence on paraffin-embedded brain of mice using different antigen retrieval methods. After 14 days of intratracheal inoculation of green fluorescent protein-tagged C. neoformans (H99-GFP), C57BL/6J mice brains were fixed in 4% paraformaldehyde and embedded in paraffin. Antigen retrieval methods such as microwaves, 1% sodium lauryl sulfate, 1 N HCl, pepsase, and tryptase were used on 5-μm paraffin sections and the effects were compared. The green fluorescence of H99-GFP persisted with antigen retrieval using 1% sodium lauryl sulfate. After immunofluorescent staining, H99-GFP, glial fibrillary acidic protein-tagged astrocytes, and ionized calcium-binding adapter molecule 1-tagged microglia could be observed clearly. Based on our results, we provide a practical approach for the further study of the interaction between C. neoformans and brain cells.
Hospital-level work organization drives the spread of SARS-CoV-2 within hospitals: insights from a multi-ward model
Authors: Oodally Ajmal , Hammami Pachka , Reilhac Astrid , Guérineau de Lamérie Guillaume , Opatowski Lulla , Temime Laura
Published: September 2021

extensive protective measures, SARS-CoV-2 widely circulates within healthcare facilities, posing a significant risk to both patients and healthcare workers. Several control strategies have been proposed; however, the global efficacy of local measures implemented at the ward level may depend on hospital-level organizational factors. We aimed at better understanding the role of between-ward interactions on nosocomial outbreaks and their control in a multiward psychiatric hospital in Western France. We built a stochastic compartmental transmission model of SARS-CoV-2 in the 24-wards hospital, accounting for the various infection states among patients and staff, and between-ward connections resulting from staff sharing. We first evaluated the potential of hospital-wide diffusion of local outbreaks, depending on the ward they started in. We then assessed control strategies, including a screening area upon patient admission, an isolation ward for COVID-19 positive patients and changes in staff schedules to limit between-ward mixing. Much larger and more frequent outbreaks occurred when the index case originated in one of the most connected wards with up to four times more transmissions when compared to the more isolated ones. The number of wards where infection spreads was brought down by up to 53 % after reducing staff sharing. Finally, we found that setting up an isolation ward reduced the number of transmissions by up to 70 %, while adding a screening area before admission seemed ineffective.

Significance Statement

Hospital acquired COVID-19 poses a major problem to many countries. Despite extensive protective measures, transmission within hospitals still occurs regularly and threatens those essential to the fight against the pandemic while putting patients at risk. Using a stochastic compartmental model, we simulate the spread of SARS-CoV-2 in a multi-ward hospital, assessing the effect of different scenarios and infection control strategies. The novelty of our method resides in the consideration of staff sharing data to better reflect the field reality. Our results highlight the poor efficiency of implementing a screening area before hospital admission, while the setting up of an isolation ward dedicated to COVID-19 patients and the restriction of healthcare workers movements between wards significantly reduce epidemic spread.
Women’s views and experiences of accessing vaccination in pregnancy during the COVID-19 pandemic: A multi-methods study in the United Kingdom
Authors: Skirrow Helen , Barnett Sara , Bell Sadie , Mounier-Jack Sandra , Kampmann Beate , Holder Beth
Published: September 2021

Background

COVID-19 changed access to healthcare, including vaccinations, in the United Kingdom (UK). This study explored UK women’s experiences of accessing pertussis vaccination during pregnancy and infant vaccinations during COVID-19.

Methods

An online cross-sectional survey was completed, between 3rd August-11 th October 2020, by 1404 women aged 16+ years who were pregnant at some point after the first UK lockdown from March 23rd, 2020. Ten follow-up semi-structured interviews were conducted.

Results

Most women surveyed were pregnant (65.7%) and a third postnatal (34.3%). Almost all women (95.6%) were aware that pertussis vaccination is recommended in pregnancy. Most pregnant (72.1%) and postnatal women (84.0%) had received pertussis vaccination; however, access issues were reported.

Over a third (39.6%) of women had a pregnancy vaccination appointment changed. COVID-19 made it physically difficult to access pregnancy vaccinations for one fifth (21.5%) of women and physically difficult to access infant vaccinations for almost half of women (45.8%). Nearly half of women (45.2%) reported feeling less safe attending pregnancy vaccinations and over three quarters (76.3%) less safe attending infant vaccinations due to COVID-19. The majority (94.2%) felt it was important to get their baby vaccinated during COVID-19.

Pregnant women from ethnic-minorities and lower-income households were less likely to have been vaccinated. Minority-ethnicity women were more likely to report access problems and feeling less safe attending vaccinations for both themselves and their babies.

Qualitative analysis found women experienced difficulties accessing antenatal care and relied on knowledge from previous pregnancies to access vaccines in pregnancy.

Conclusion

During the ongoing and future pandemics, healthcare services should prioritise equitable access to routine vaccinations, including tailoring services for ethnic-minority families who experience greater barriers to vaccination.

Highlights

Access to pregnancy vaccines in the United Kingdom was disrupted by the COVID-19 pandemic.

UK women reported difficulties in physically accessing vaccine appointments and feeling less safe accessing vaccine appointments for themselves when pregnant and for their babies during COVID-19, with women from ethnic minorities in the UK were more likely to report difficulties.

Vaccine services must ensure equitable access to vaccine appointments during the ongoing COVID-19 pandemic including tailoring services for lower income and ethnic minority families.
Prevalence, severity, and risk factors of disability among adults living with HIV accessing routine outpatient HIV care in London, United Kingdom (UK): A cross-sectional self-report study
Authors: Brown Darren A , O’Brien Kelly K , Harding Richard , Sedgwick Philip , Nelson Mark , Boffito Marta , Lewko Agnieszka
Published: September 2021

Objectives

Measure the prevalence and severity of disability, and examine disability risk factors among adults living with HIV in London, United Kingdom (UK).

Methods

We conducted a quantitative cross-sectional study. The following self-reported questionnaires were administered: World Health Organization Disability Assessment Schedule 2.0 (WHODAS), HIV Disability Questionnaire (HDQ), a disability item using the Equality Act disability definition (EADD), and demographic and HIV questionnaire. We calculated the proportion (95% Confidence Interval; CI) of “severe” and “moderate” disability as measured using EADD and WHODAS scores ≥2 respectively. We measured disability severity with HDQ domain severity scores. We used demographic and HIV characteristic questionnaire responses to assess potential risk factors of “severe” (EADD) and “moderate” (WHODAS scores ≥2) disability using logistic regression analysis, and HDQ severity domain scores using linear regression analysis.

Results

Of 201 participants, 176 (87.6%) identified as men, with median age 47 years, and 194 (96.5%) virologically suppressed. Severe disability prevalence was 39.5% (n=79/201), 95% CI [32.5%, 46.4%]. Moderate disability prevalence was 70.5% (n=141/200), 95% CI [64.2%, 76.8%]. Uncertainty was the most severe HDQ disability domain. The HIV characteristic of late HIV diagnosis was a risk factor for severe disability [Odds Ratio (OR) 2.71; CI 1.25, 5.87]. The social determinants of health economic inactivity [OR 2.79; CI 1.08, 7.21] and receiving benefits [OR 2.87; CI 1.05, 7.83] were risk factors for “severe” disability. Economic inactivity [OR 3.14; CI 1.00, 9.98] was a risk factor for “moderate” disability. Economic inactivity, receiving benefits, and having no fixed abode were risk factors (P≤0.05) across HDQ disability domains; physical, mental and emotional, difficulty with day-to-day activities, and challenges to social participation. Personal factors of identifying as a woman and being aged <50 years were risk factors (P≤0.05) for HDQ disability domains; mental and emotional, uncertainty, and challenges with social participation.

Conclusions

People living with well-controlled HIV in London UK experienced multi-dimensional and episodic disability. Results help to better understand the prevalence, severity, and risk factors of disability experienced by adults living with HIV, identify areas to target interventions, reduce disability, and optimise health and function.
Population-based Cross-sectional Analysis of the Epidemiology of the Surgical Correction of Hyperhidrosis in 1216 Patients over 11 years
Authors: da Silva Marcelo Fiorelli Alexandrino , Louzada Andressa Cristina Sposato , Teivelis Marcelo Passos , Stabellini Nickolas , Leiderman Dafne Braga Diamante , de Campos José Ribas Milanez , Amaro Edson , Wolosker Nelson
Published: September 2021

Abstract

Background

Endoscopic thoracic sympathectomy is the definitive surgical treatment for hyperhidrosis, and a nationwide study suggested that it has been performed in a higher rate than which could have been expected due to climate characteristics, comparing to the national statistics.

Objectives

To study the epidemiology of sympathectomy to treat hyperhidrosis in São Paulo, the largest city in the Southeast.

Design and setting

population-based cross-sectional study.

Methods

data on sympathectomies to treat hyperhidrosis between 2008 and 2018 were assessed from the database of the Municipal Health Secretary of São Paulo, Brazil.

Results

65.29% of the patients were female, 66.2% aged between 20 and 39 years and 37.59% had addresses registered outside São Paulo. 1216 procedures were performed in the city of São Paulo from 2008 to 2018, 78.45% of which in only two public hospitals. The number of procedures significantly declined over the years (p = 0.001). 71.63% of the procedures were associated with 2 to 3 days of hospital stay, only 78 intensive care unit days were billed and we did not observe any intra-hospital death.

Conclusions

sympathectomies for the treatment of HH were widely performed in the city of São Paulo (1216 procedures), mainly in young (20 -39 years) and female patients, with more than one third of the patients having addresses registered outside the city. This is a very safe surgery, with low need for intensive care units and no mortality in our series. There was a decreasing trend in the number of surgeries over the years.
Development of a new militarily-relevant whole-body low-intensity blast model for mild and subconcussive traumatic brain injury: Examination of acute neurological and multi-organ pathological outcomes
Authors: Hellewell Sarah C. , Cernak Ibolja
Published: September 2021

This work describes a newly developed experimental mouse model reproducing features of blast-induced neurotrauma (BINT), induced in operationally relevant manner using a compressed air-driven shock tube. Mild BINT (smBINT) was induced by one exposure to a low-intensity blast (LIB), whereas subconcussive BINT (rscBINT) was caused by repeated exposures to LIB.

To mimic an operational scenario when a soldier is standing when exposed to blast using a quadruped experimental animal (mouse), a whole-body holder was developed to position mice in a bipedal stance, face-on toward the pressure wave generated in a shock tube. This restraint avoids ‘bobble head’ movement, thus prevents tertiary blast effects, and allows administration of fast-acting inhaled anesthetics via nose cone.

Using this model, we established and validated paradigms for primary blast-induced mild and repetitive traumatic brain injuries Our results showed that a single exposure to 69 kPa (10 psi) was capable of inducing smBINT, whereas three-rounds of exposure to 41 kPa (6 psi) caused rscBINT.

Mice recovered rapidly from both types of BINT without prolonged neurological dysfunction. Mild superficial pathology was found predominantly in the lungs 24h after injury, with equivalent pathology after smBINT or repetitive rscBINT. The Purkinje layer of the cerebellum exhibited neuronal damage persisting up to 7d. Similar to some other models as well as clinical findings, this model reproduces blast-induced cerebellar pathology. In conclusion, this model positioning mice in a bipedal stance and facing front-on toward the shockwave provides realistic representation of operational scenarios and reproduces militarily-relevant smBINT and rscBINT in the laboratory.
Hierarchical autoencoder-based integration improves performance in multi-omics cancer survival models through soft modality selection
Authors: Wissel David , Rowson Daniel , Boeva Valentina
Published: September 2021

With decreasing costs of high-throughput sequencing, more and more datasets providing omics profiles of cancer patients become available. Thus, novel survival analysis approaches integrating these differently sized and heterogeneous molecular and clinical groups of variables start being developed. Due to the difficulty of the task of multi-omics data integration, the Cox Proportional-Hazards (PH) model using clinical data has remained one of the best-performing techniques, barely outperformed by models using molecular data modalities. There is therefore a need for methods that can successfully perform multi-omics integration in survival analysis and outperform the clinical Cox PH model. Moreover, while certain deep learning methods have been shown to provide state-of-the-art accuracy of cancer survival prediction, most of them show no benefit or even decay in performance when integrating a larger number of modalities, further motivating a need to investigate how modality-specific representations should be integrated when using neural networks for multi-omics integration. We benchmarked multiple integration techniques for a neural network architecture, revealing that hierarchical autoencoder-based integration of modality-specific representations outperformed other methods such as max-pooling and was comparable with state-of-the-art statistical approaches for multi-omics integration. Further, we showed that the hierarchical autoencoder-based integration of modality-specific representations achieved increased performance through a soft modality selection mechanism, focusing on the most informative modalities for each cancer. We thus framed multiomics integration as a partial group-wise feature selection problem, highlighting that only those models performed well that could adequately weight important modalities in the presence of the high noise imposed by less important modalities.
Single-molecule Dynamic In-Solution Inhibition Assay: A Method for Full Kinetic Profiling of Drug Candidate Binding to GPCRs in Native Membranes
Authors: Kaminski Tim , Zhdanov Vladimir P. , Höök Fredrik
Published: September 2021

Kinetic profiling of drug–target interactions using surface-based label-free technologies is well established for water-soluble pharmaceutical targets but is difficult to execute for membrane proteins in general and G-protein–coupled receptors (GPCRs) in particular. That is because surface immobilization of GPCRs tends to alter their configuration and function, leading to low target coverage and non-specific binding. We here describe a novel assay for kinetic profiling of drug binding to the GPCR human beta 2 adrenergic receptor (β2AR). The assay involves temporally-resolved imaging of the binding of individual β2AR-containing cell membrane-derived liposomes to a surface-immobilized ligand in the presence of screened drugs. This approach allowed to determine association and dissociation constants of β2AR and suspended alprenolol (antagonist) and fenoterol (agonist). The set-up combines a 384 well-plate sensor chip with automated liquid handling and the assay takes minutes to complete, making it well adapted for drug screening campaigns.
Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein
Authors: Castro Julia T. , Fumagalli Marcílio J. , Hojo-Souza Natalia S. , Azevedo Patrick , Salazar Natalia , Rattis Bruna , Ramos Simone G. , Faustino Lídia , Almeida Gregório G. , Oliveira Livia I. , Marçal Tomas G. , Augusto Marconi , Magalhães Rubens , Cassaro Bruno , Burle Gabriela , Doro Daniel , Kalil Jorge , Durigon Edson , Salazar Andrés , Caballero Otávia , Machado Alexandre , Silva João S. , da Fonseca Flávio , Fernandes Ana Paula , Teixeira Santuza R. , Gazzinelli Ricardo T.
Published: September 2021

The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFNγ response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies. Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome, lung inflammation and lethality. Thus, the N protein should be considered to induce T-cell-based immunity to improve SARS-CoV-2 vaccines, and eventually to circumvent the immune scape by variants.
A novel variant in DYNC1H1 could contribute to human amyotrophic lateral sclerosis-frontotemporal dementia spectrum.
Authors: Mentis Alexios-Fotios , Vlachakis Dimitrios , Papakonstantinou Eleni , Zaganas Ioannis , Patrinos George P. , Chrousos George P. , Dardiotis Efthimios
Published: September 2021

Amyotrophic lateral sclerosis (ALS) belongs to the ALS-frontotemporal dementia (FTD) spectrum and is hallmarked by upper and lower motor neuron degeneration. Here, we present a patient with a cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) pathogenic variant who fulfilled the ALS El Escorial criteria, and we review relevant literature. Using whole-exome sequencing, we identified a deleterious point variant in DYNC1H1 [c.4106A>G (p. Q1369R))] as a likely contributor to the ALS phenotype. In silico structural analysis, molecular dynamics simulation, and protein stability analysis predicted that this variant may increase DYNC1H1 protein stability. Moreover, this variant may disrupt binding of the transcription factor TFAP4, thus potentially acting as duon. Since a) DYNC1H1 forms part of a ubiquitous eukaryotic motor protein complex, and b) disruption of dynein function by perturbation of the dynein-dynactin protein complex is implicated in other motor neuron degenerative conditions, this variant could disrupt processes like retrograde axonal transport, neuronal migration, and protein recycling. Our findings expand the heterogenous spectrum of DYNC1H1 pathogenic variants−associated phenotype and prompt further investigations of the role of this gene in ALS.
Developing a framework for fire safety management plan: the case of Malaysia's public hospital buildings
Authors: Jaafar Mastura , Salim Nuzaihan Aras Agus , Salleh Naziah Muhamad , Sulieman Mohd Zailan , Ulang Norhidayah Md , Ebekozien Andrew
Published: September 2021

Purpose

Globally, several studies have shown that hospital building is charged with multiple inherent risks because a large number of users are vulnerable in tragic events. Thus, the need for the fire safety management plan (FSMP) has been proved as an instrument to mitigate fire and related risks in healthcare facilities. In Malaysia, FSMP regarding public healthcare building is yet to be explored in-depth. Therefore, this paper explores the information necessary to develop the FSMP framework for public hospital buildings.

Design/methodology/approach

The paper’s objectives were accomplished via a combination of five face-to-face interviews and observations of five selected public hospitals in Pulau Pinang, Malaysia. The five key participants were across the five public hospitals and collated data analysed through thematic analysis with the assistance of MAXQDA 2018.

Findings

Findings show that fire safety stakeholders practice system, fire safety action plan and fire risk management were the three main variables that promote fire safety programme and will improve FSMP for Malaysia’s public hospital buildings.

Research limitations/implications

This paper’s data collection is limited to Penang, Malaysia, and a qualitative research approach was used, but this does not deteriorate the strength of the findings. Future studies are needed to consider validating findings from this paper via a quantitative approach.

Practical implications

The suggested framework can be employed by Malaysia’s public hospital authorities as a guideline to mitigate fire hazards in the country’s healthcare facilities.

Originality/value

This paper is encouraging hospital operators and other key stakeholders to improve on their FSMP for healthcare buildings across Malaysia as part of the study implications.