bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment outcomes of tuberculosis patients and associated factors in Bale Zone, Southeast Ethiopia: a retrospective study
Authors: Woldemichael Bedasa , Darega Jiregna , Dida Nagasa , Tesfaye Tamiru
Published: February 2021

Objective

This study assessed the outcome of tuberculosis treatment and associated factors in Bale Zone, Southeast Ethiopia in 2017.

Methods

This was 5-year retrospective study of a health registry for tuberculosis patients, which was reviewed from 1 September 2011 to 30 August 2016. Data were analyzed, and descriptive and logistic regression analyses were used to identify the factors that were associated with tuberculosis treatment outcomes.

Results

Among the 7205 tuberculosis patients, 6325 (87.8%) had a successful treatment outcome and 880 (12.2%) had an unsuccessful outcome. The age groups ≤14 years (adjusted odds ratio [AOR]=2.21), 15 to 24 years (AOR=1.61), 25 to 34 years (AOR=1.86), or 35 to 44 years (AOR=1.65); being treated at a hospital (AOR=1.63) or health center (AOR=2.52); pulmonary tuberculosis-positive (AOR=0.80); or extrapulmonary tuberculosis patients (AOR= 0.78) were the factors that were significantly associated with tuberculosis treatment outcome.

Conclusions

Public health facilities should pay special attention to the identified variables for tuberculosis prevention and control activities, especially focusing on supporting health workers who work at a health post (lowest level of Ethiopia’s three-tiered healthcare system).
Downward Spiral of Bullying: Victimization Timeline From Former Victims’ Perspective
Authors: Wójcik Małgorzata , Thornberg Robert , Flak Wojciech , Leśniewski Jakub
Published: February 2021

The present study aimed to investigate how those who had been chronic victims of bullying perceive their bullying experience from their initial attacks to their bullying exit, how they understood processes and actions causing a situation to become progressively worse, and how they interpreted their own coping behaviors. Nine individuals who were victimized for at least 6 years were interviewed. The grounded theory approach was used to analyze the data, which generated a grounded theory of the downward spiral of bullying, demonstrating hidden aspects of bullying—the victim’s inner process as a response to external victimizing and accompanying events. The interdependence of those processes is presented in a timeline to show their cumulative nature as new vicious circles of bullying involving maladaptive coping strategies (e.g., self-blame), which form an overriding pattern of behavior that renders victims unable to break it even if they enter a new peer group. In terms of policy implications, the findings suggest the need to introduce school transition programs supporting school adaptation, identify chronic victims, and take every victimhood narrative seriously.
Social Roots of Local Politics: Women Contestants in the Panchayat Elections of Uttar Pradesh (2015)
Authors: Mukerji Siddhartha
Published: February 2021

Competitiveness is a sign of progress in both economic and political arenas. There has been a significant rise in the number of contestants and heightened competition in the 2015 elections of village heads in Uttar Pradesh in which women contested in large numbers. The institutional incentive of the 73rd Amendment to the Constitution certainly acted as a booster. But an empirical account of people’s perceptions presents an untold story of social institutionalization which reinforces the submissiveness of women who contest elections primarily for preserving family position and prestige and rarely out of independent choice. The study takes a closer look at the factors that trigger higher contestation and women’s participation as candidates in village head elections. The study goes beyond the explanations offered by top-down approaches to electoral democracy and institutional studies of decentralization to account for specificities of gender dynamics in local politics.
Creep damage and fracture of notched specimens under static and fast periodic loading
Authors: Breslavsky D , Senko A , Tatarinova O
Published: February 2021

Creep-damage processes in notched specimens subjected to static and periodic loading are studied experimentally. Subsequent simulations were carried out using Rabotnov evolution equation. In case of dynamic creep (fast periodic loading) the constitutive equations derived by use of asymptotic and averaging methods were used. Numerical results were obtained by the combination of FEM and predictor-corrector time integration scheme. Fracture process was studied using designed numerical procedure based on the elimination of the finite elements with critical values of damage parameter. The fracture times and directions of the crack propagation were determined. The qualitative difference between processes of crack propagation in cases of static and periodic loading were observed.
A Sum Score to Define Therapy-Refractory Myasthenia Gravis: A German Consensus
Authors: Schroeter Michael , Berger Benjamin , Blaes Franz , Hagenacker Tim , Jander Sebastian , Kaiser Julia , Kalischewski Petra , Lee De-Hyung , Ruck Tobias , Schara Ulrike , Urban Peter , Meisel Andreas
Published: February 2021

Background and purpose:

In 2017, eculizumab has been approved for treatment-refractory generalised myasthenia gravis (TRgMG). The German Myasthenia Foundation has published a consensus statement on the use of eculizumab, with a recent update. However, a treatment-refractory state is still ill-defined and the term warrants further clarification. We aimed at developing a sum score to operationalise the definition of a TRgMG status, which is easy- to-handle in clinical decision making.

Methods:

We established a structured consensus process according to the Delphi consensus methodology, with 12 members of the medical advisory board of the German Myasthenia Foundation. Accordingly, 4 consensus rounds were accomplished. Additionally, a literature survey covering the years 2004-2020 was done and relevant information offered to the consensus group. Consensus criteria were predefined. In the consensus process the relative importance of scoring items were to be consented, with a sum score of 20 and above indicating a TRgMG status.

Results:

The sum score considers the categories disease severity, inefficiency of antecedent therapies, cessation of therapies due to side effects, and long term stay on the intensive care unit. Categories were specified by a total of 13 scoring items. Eventually, the Delphi process developed an unanimous scoring consensus.

Conclusion:

We suggest a sum score to define treatment refractory state in generalised myasthenia gravis. Beyond clarifying the indication of eculizumab, this easy-to-handle score facilitates clinical decision making and offers new inclusion criteria for clinical studies that explore new therapeutic perspectives in myasthenia gravis treatment.
Stroke case fatality in sub-Saharan Africa: Systematic review and meta-analysis
Authors: Adoukonou Thierry , Kossi Oyéné , Fotso Mefo Pervenche , Agbétou Mendinatou , Magne Julien , Gbaguidi Glwadys , Houinato Dismand , Preux Pierre-Marie , Lacroix Philippe
Published: February 2021

Background

The burden of stroke is high in sub-Saharan Africa; however, few data are available on long-term mortality.

Objective

To estimate over one-month stroke case fatality in sub-Saharan Africa.

Methods

A systematic review and meta-analysis were performed according to meta-analysis of observational studies in epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42020192439), on five electronic databases (PubMed, Science direct, AJOL, EMBASE, and Web of Sciences). We searched all studies on stroke case fatality over one month in sub-Saharan Africa published between 1st January 2000 and 31st December 2019.

Results

We included 91 studies with a total of 34,362 stroke cases. The one-month pooled stroke case-fatality rate was 24.1% [95% CI: 21.5–27.0] and 33.2% [95% CI: 23.6–44.5] at one year. At three and five years, the case-fatality rates were respectively 40.1% [95% CI: 20.8–63.0] and 39.4% [95% CI: 14.3–71.5] with high heterogeneity. Hemorrhagic stroke was associated with a higher risk of mortality at one month, but ischemic stroke increased the risk of mortality over six months. Diabetes was associated with poor prognosis at 6 and 12 months with odds ratios of 1.64 [95% CI: 1.22–2.20] and 1.85 [1.25–2.75], respectively.

Conclusion

The stroke case fatality over one month was very high, compared to case fatalities reported in Western countries and can be explained by a weak healthcare systems and vascular risk factors.
A Review of the Collagen Orientation in the Articular Cartilage
Authors: Bloebaum Roy D. , Wilson Andrew S. , Martin William N.
Published: February 2021

Objective

There has been a debate as to the alignment of the collagen fibers. Using a hand lens, Sir William Hunter demonstrated that the collagen fibers ran perpendicular and later aspects were supported by Benninghoff. Despite these 2 historical studies, modern technology has conflicting data on the collagen alignment.

Design

Ten mature New Zealand rabbits were used to obtain 40 condyle specimens. The specimens were passed through ascending grades of alcohol, subjected to critical point drying (CPD), and viewed in the scanning electron microscope. Specimens revealed splits from the dehydration process. When observing the fibers exposed within the opening of the splits, parallel fibers were observed to run in a radial direction, normal to the surface of the articular cartilage, radiating from the deep zone and arcading as they approach the surface layer. After these observations, the same samples were mechanically fractured and damaged by scalpel.

Results

The splits in the articular surface created deep fissures, exposing parallel bundles of collagen fibers, radiating from the deep zone and arcading as they approach the surface layer. On higher magnification, individual fibers were observed to run parallel to one another, traversing radially toward the surface of the articular cartilage and arcading. Mechanical fracturing and scalpel damage induced on the same specimens with the splits showed randomly oriented fibers.

Conclusion

Collagen fiber orientation corroborates aspects of Hunter’s findings and compliments Benninghoff. Investigators must be aware of the limits of their processing and imaging techniques in order to interpret collagen fiber orientation in cartilage.
Addressing Anxiety and Fear during the Female Pelvic Examination
Authors: O’Laughlin Danielle J. , Strelow Brittany , Fellows Nicole , Kelsey Elizabeth , Peters Sonya , Stevens Joy , Tweedy Johanna
Published: February 2021

To review the anxiety and fear risk factors, pathophysiology, symptoms, screening and diagnosis while highlighting treatment considerations for women undergoing a pelvic examination.

Methods:

We reviewed the literature pertaining to anxiety and fear surrounding the pelvic examination to help guide health care providers’ on available screening options and to review options for individualized patient management.

Results:

Anxiety and fear are common before and during the pelvic examination. In fact, the pelvic exam is one of the most common anxiety-provoking medical procedures. This exam can provoke negative physical and emotional symptoms such as pain, discomfort, anxiety, fear, embarrassment, and irritability. These negative symptoms can interfere with preventative health screening compliance resulting in delayed or avoided care and significant health consequences.

Conclusion:

Assessing women for anxiety related to pelvic examinations may help decrease a delay or avoidance of examinations. Risk factor and symptom identification is also a key component in this. General anxiety questionnaires can help identify women with anxiety related to pelvic examinations. Strategies to reduce anxiety, fear and pain during a pelvic examination should routinely be implemented, particularly in women with high-risk factors or those identified with screening techniques as having anxiety, fear or pain with examinations. Treatment options should be targeted at understanding the patient’s concerns, starting conversations about pelvic examinations early, educating patient’s about the examination and offering the presence of a chaperone or support person. During an examination providers should ensure the patient is comfortable, negative phrases are avoided, the correct speculum size is utilized and proper lubrication, draping, dressing and positioning are performed. Treating underlying gynecologic or mental health conditions, consideration of cognitive behavioral therapy and complementary techniques such as lavender aromatherapy and music therapy should also be considered when appropriate.
Interbundle Impingement Pressure in Individualized and Nonindividualized Double-Bundle Anterior Cruciate Ligament Reconstruction: A Cadaveric Study
Authors: Wu Bing , Liang Daqiang , Yang Lei , Li Sheng , Qiu Zhihe , Qin Qihuang , Liang Xinzhi , Liu Haifeng , Ouyang Kan , Xiong Jianyi , Wang Daping , Lu Wei , Zhong Mingjin , Li Ying , Li Hao , Feng Wenzhe , Chen Kang , Peng Liangquan , Zhu Weiming
Published: February 2021

Background:

Graft impingement is one of the main concerns in double-bundle anterior cruciate ligament reconstruction (DB-ACLR). Impingement between the anteromedial (AM) and posterolateral (PL) bundles has been postulated to cause graft deterioration or rerupture, but this has not been thoroughly investigated, and the interbundle impingement pressure (IIP) has not been well researched.

Purpose:

To determine the IIP between the AM and PL bundles in the native anterior cruciate ligament (ACL) and in DB-ACLR with individualized and nonindividualized double-tunnel placement.

Study Design:

Controlled laboratory study.

Methods:

A total of 30 fresh-frozen, nonpaired, human cadaveric knees were randomly divided into 3 groups of 10 knees: native intact ACL (NI group), DB-ACLR tunnel placement using the preserved remnant procedure (individualized reconstruction) (PR group), and DB-ACLR tunnel placement using the bony landmark procedure (nonindividualized reconstruction) (BL group). Pressure sensors were inserted between the AM and PL bundles. The knee was moved passively from full extension to full flexion, and the IIP between the 2 ACL bundles was measured every 15°. Similarly, the impingement pressure was measured between the ACL and intercondylar roof and between the ACL and posterior cruciate ligament (PCL).

Results:

No significant differences were found in the maximum, mean, or minimum ACL-roof and ACL-PCL impingement pressures among the 3 groups. The IIP significantly increased when the knee joint was flexed >120° in all 3 groups ( P < .001). Compared with the other 2 groups, the BL group had significantly higher maximum and mean IIP throughout the range of knee movement ( P < .001) and from maximum extension to 120° of flexion ( P < .001). The BL group also had significantly higher minimum IIP than the other 2 groups when knee flexion was >120° ( P < .001). No significant differences were seen in maximum, minimum, or mean IIP between the NI and PR groups.

Conclusion:

The PR procedure (individualized DB-ACLR) was more consistent with the interbundle biomechanical conditions of the native ACL, whereas the BL procedure (nonindividualized DB-ACLR) had higher maximum and mean IIP. The IIP was higher than the ACL–intercondylar roof or ACL-PCL pressures, and it increased significantly when knee flexion was >120°.

Clinical Relevance:

These data suggest that surgeons can perform individualized DB-ACLR using preserved remnants for tunnel placement as impingement-free DB-ACLR.
Restoring RUNX1 deficiency in RUNX1 familial platelet disorder by inhibiting its degradation
Authors: Krutein Michelle C. , Hart Matthew R. , Anderson Donovan J. , Jeffery Jasmin , Kotini Andriana G. , Dai Jin , Chien Sylvia , DelPriore Michaela , Borst Sara , Maguire Jean Ann , French Deborah L. , Gadue Paul , Papapetrou Eirini P. , Keel Siobán B. , Becker Pamela S. , Horwitz Marshall S.
Published: February 2021

RUNX1 familial platelet disorder (RUNX1-FPD) is an autosomal dominant disorder caused by a monoallelic mutation of RUNX1, initially resulting in approximately half-normal RUNX1 activity. Clinical features include thrombocytopenia, platelet functional defects, and a predisposition to leukemia. RUNX1 is rapidly degraded through the ubiquitin-proteasome pathway. Moreover, it may autoregulate its expression. A predicted kinetic property of autoregulatory circuits is that transient perturbations of steady-state levels result in continued maintenance of expression at adjusted levels, even after inhibitors of degradation or inducers of transcription are withdrawn, suggesting that transient inhibition of RUNX1 degradation may have prolonged effects. We hypothesized that pharmacological inhibition of RUNX1 protein degradation could normalize RUNX1 protein levels, restore the number of platelets and their function, and potentially delay or prevent malignant transformation. In this study, we evaluated cell lines, induced pluripotent stem cells derived from patients with RUNX1-FPD, RUNX1-FPD primary bone marrow cells, and acute myeloid leukemia blood cells from patients with RUNX1 mutations. The results showed that, in some circumstances, transient expression of exogenous RUNX1 or inhibition of steps leading to RUNX1 ubiquitylation and proteasomal degradation restored RUNX1 levels, thereby advancing megakaryocytic differentiation in vitro. Thus, drugs retarding RUNX1 proteolytic degradation may represent a therapeutic avenue for treating bleeding complications and preventing leukemia in RUNX1-FPD.
Correction to: Homology analysis between clinically isolated extraintestinal and enteral Klebsiella pneumoniae among neonates
Authors: Chen Chun-mei , Wang Min , Li Xian-ping , Li Peng-ling , Tian Jing-jing , Zhang Kan , Luo Can
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Index of microcirculatory resistance predicts long term cardiac systolic function in patients with STEMI undergoing primary PCI
Authors: Qi Yu , Gu Rong , Xu Jiamin , Kang Lina , Liu Yihai , Wang Lian , Chen Jianzhou , Zhang Jingmei , Wang Kun
Published: February 2021

Background

To evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI).

Methods

A total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year.

Results

The ratio of TMPG (TIMI myocardial perfusion grade) 3 (85.7% vs. 52%, p = 0.015) and STR (ST-segment resolution) > 70% (82.1% vs. 48%, p = 0.019) were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months (43.06 ± 2.63% vs. 40.20 ± 2.67%, p < 0.001) and 1 year (44.16 ± 2.40% vs. 40.13 ± 3.48%, p < 0.001). IMR was negatively correlated with LVEF at 3 months (r = − 0.1014, p = 0.0040) and 1 year (r = − 0.1754, p < 0.0001).

Conclusions

The IMR showed significant negative correlation with the LVEF value after primary PCI. The high IMR is a strong predictor of heart failure within 1 year after anterior myocardial infarction.
Correction to: Failure to maintain full-term pregnancies in pig carrying klotho monoallelic knockout fetuses
Authors: Lee Sanghoon , Jung Min Hee , Song Kilyoung , Jin Jun-Xue , Taweechaipaisankul Anukul , Kim Geon A. , Oh Hyun Ju , Koo Ok Jae , Park Se Chang , Lee Byeong Chun
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Effect of remote online exam delivery on student experience and performance in applied knowledge tests
Authors: Jaap Alan , Dewar Avril , Duncan Colin , Fairhurst Karen , Hope David , Kluth David
Published: February 2021

Background

The use of remote online delivery of summative assessments has been underexplored in medical education. Due to the COVID-19 pandemic, all end of year applied knowledge multiple choice question (MCQ) tests at one UK medical school were switched from on campus to remote assessments.

Methods

We conducted an online survey of student experience with remote exam delivery and compared test performance in remote versus invigilated campus-based forms of similar assessments for Year 4 and 5 students across two academic years.

Results

Very few students experienced technical or practical problems in completing their exam remotely. Test anxiety was reduced for some students but increased for others. The majority of students preferred the traditional setting of invigilated exams in a computer lab, feeling this ensured an even playing field for all candidates. Mean score was higher for Year 4 students in the remotely-delivered versus campus-based form of the same exam (76.53% [SD 6.57] vs. 72.81% [6.64];t438.38 = 5.94,p = 0.001;d = 0.56), whereas candidate performance was equivalent across both forms for Year 5 students.

Conclusions

Remote online MCQ exam delivery is an effective and generally acceptable approach to summative assessment, and could be used again in future without detriment to students if onsite delivery is not possible.
The effect of salinity on Enterocytozoon hepatopenaei infection in Penaeus vannamei under experimental conditions
Authors: Aranguren Caro L. F. , Alghamdi F. , De Belder K. , Lin J. , Mai H. N. , Millabas J. , Alrehaili Y. , Alazwari A. , Algetham S. , Dhar A. K.
Published: February 2021

Background

Enterocytozoon hepatopenaei (EHP) is an enteric pathogen that affects Penaeus vannamei and Penaeus monodon shrimp in many SE Asian countries. In the western hemisphere, EHP was reported for the first time in 2016 in farmed P. vannamei in Venezuela. Anecdotal evidence suggests that EHP is more prevalent in grow-out ponds where the salinity is high (> 15 parts per thousand (ppt)) compared to grow-out ponds with low salinities (< 5 ppt). Considering that P. vannamei is an euryhaline species, we were interested in knowing if EHP can propagate in P. vannamei in low salinities.

Results

In this study, we described an experimental infection using fecal strings as a source inoculum. Specific Pathogen Free (SPF) P. vannamei were maintained at three different salinities (2 ppt, 15 ppt, and 30 ppt) while continuously challenged using feces from known EHP-infected P. vannamei over a period of 3 weeks. The fecal strings, used as a source of EHP inocula in the challenges, was sufficient to elicit an infection in shrimp maintained at the three salinities. The infectivity of EHP in shrimp reared at 2 ppt, 15 ppt, and 30 ppt salinities was confirmed by PCR and histopathology. The prevalence and the severity of the EHP infection was higher at 30 ppt than at 2 ppt and 15 ppt.

Conclusion

The data suggests that fecal strings are a reliable source of EHP inoculum to conduct experimental challenges via the fecal-oral route. An EHP infection can occur at a salinity as low as 2 ppt, however, the prevalence and the severity of the EHP infection is higher at a salinity of 30 ppt.
Correction to: Pulmonary edema following central nervous system lesions induced by a non-mouse-adapted EV71 strain in neonatal BALB/c mice
Authors: Jin Yuefei , Zhang Chao , Zhang Rongguang , Ren Jingchao , Chen Shuaiyin , Sui Meili , Zhou Guangyuan , Dang Dejian , Zhu Jiehui , Feng Huifen , Xi Yuanlin , Yang Haiyan , Duan Guangcai
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Chiropractic students’ cognitive dissonance to statements about professional identity, role, setting and future: international perspectives from a secondary analysis of pooled data
Authors: Swain Michael S. , Gliedt Jordan A. , de Luca Katie , Newell Dave , Holmes Michelle
Published: February 2021

Background

Chiropractic students demonstrate philosophically opposing views about the chiropractic profession. The primary aim was to describe chiropractic students’ responses to statements about chiropractic identity, role, setting, and future direction. A secondary aim was to describe the frequency of internally conflicting responses.

Methods

Three datasets from Europe, North America, and Australia/New Zealand were pooled in a secondary data analysis. Chiropractic students from 25 chiropractic training institutions completed interrelating surveys (combined response rate 21.9%) between 2013 and 2018. The survey instrument investigated student viewpoints about chiropractic professional identity, role, practice setting and future direction of chiropractic practice. Student attitudes about chiropractic were described using weighted proportions to adjust for unequal population sampling across the three geographical regions. The frequency of concordant and discordant student responses was described by combining identity items with items that explored responses about practice role, setting and future direction. The relationship between student characteristics (age, sex, education, association membership and geographical region) and ideologically conflicting responses were assessed using the Chi-squared test and Cramér’s V.

Results

Data from 2396 student chiropractors (50.8% female; from Europe 36.2%, North America 49.6% and Australia/New Zealand 14.5%) were analysed. For identity, nearly half of the chiropractic students (weighted 45.1%) agreed that it is important for chiropractors to hold strongly to the traditional chiropractic theory that adjusting the spine corrects “dis-ease” and agreed (weighted 55.5%) that contemporary and evolving scientific evidence is more important than traditional chiropractic principles. The frequency of discordant (ideologically conflicting) student responses ranged from 32.5% for statements about identity versus role, to 51.4% for statements about identity versus future. There was no association between student age, sex and internally conflicting responses. Chiropractic students’ professional association membership status, pre-chiropractic education and geographical region were associated with ideologically conflicting responses.

Conclusions

Chiropractic students in this analysis show traditional and progressive attitudes towards the chiropractic profession. Individual student responses frequently contradict in terms of professional ideology, but most (approximately half) students demonstrate concordant progressive and mainstream attitudes. Ideological conflict may raise concerns about some students’ ability to learn and make clinical judgements, and potential for disharmony in the chiropractic fraternity.
The epidemiology and clinical outcomes of ventilator-associated events among 20,769 mechanically ventilated patients at intensive care units: an observational study
Authors: He Qiao , Wang Wen , Zhu Shichao , Wang Mingqi , Kang Yan , Zhang Rui , Zou Kang , Zong Zhiyong , Sun Xin
Published: February 2021

Background

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection (HAI) in intensive care units (ICUs). Ventilator-associated event (VAE), a more objective definition, has replaced traditional VAP surveillance and is now widely used in the USA. However, the adoption outside the USA is limited. This study aims to describe the epidemiology and clinical outcomes of VAEs in China, based on a prospectively maintained registry.

Methods

An observational study was conducted using an ICU-HAI registry in west China. Patients that were admitted to ICUs and underwent mechanical ventilation (MV) between April 1, 2015, and December 31, 2018, were included. The characteristics and outcomes were compared between patients with and without VAEs. The rates of all VAEs dependent on different ICUs were calculated, and the pathogen distribution of patients with possible VAP (PVAP) was described.

Results

A total of 20,769 ICU patients received MV, accounting for 21,723 episodes of mechanical ventilators and 112,697 ventilator-days. In all, we identified 1882 episodes of ventilator-associated condition (VAC) events (16.7 per 1000 ventilator-days), 721 episodes of infection-related ventilator-associated complications (IVAC) events (6.4 per 1000 ventilator-days), and 185 episodes of PVAP events (1.64 per 1000 ventilator-days). The rates of VAC varied across ICUs with the highest incidence in surgical ICUs (23.72 per 1000 ventilator-days). The median time from the start of ventilation to the onset of the first VAC, IVAC, and PVAP was 5 (3–8), 5 (3–9), and 6 (4–13) days, respectively. The median length of hospital stays was 28.00 (17.00–43.00), 30.00 (19.00–44.00), and 30.00 (21.00–46.00) days for the three VAE tiers, which were all longer than that of patients without VAEs (16.00 [12.00–23.00]). The hospital mortality among patients with VAEs was more than three times of those with non-VAEs.

Conclusions

VAE was common in ICU patients with ≥ 4 ventilator days. All tiers of VAEs were highly correlated with poor clinical outcomes, including longer ICU and hospital stays and increased risk of mortality. These findings highlight the importance of VAE surveillance and the development of new strategies to prevent VAEs.
De novo design and bioactivity prediction of SARS-CoV-2 main protease inhibitors using recurrent neural network-based transfer learning
Authors: Santana Marcos V. S. , Silva-Jr Floriano P.
Published: February 2021

The global pandemic of coronavirus disease (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) created a rush to discover drug candidates. Despite the efforts, so far no vaccine or drug has been approved for treatment. Artificial intelligence offers solutions that could accelerate the discovery and optimization of new antivirals, especially in the current scenario dominated by the scarcity of compounds active against SARS-CoV-2. The main protease (Mpro) of SARS-CoV-2 is an attractive target for drug discovery due to the absence in humans and the essential role in viral replication. In this work, we developed a deep learning platform for de novo design of putative inhibitors of SARS-CoV-2 main protease (Mpro). Our methodology consists of 3 main steps: (1) training and validation of general chemistry-based generative model; (2) fine-tuning of the generative model for the chemical space of SARS-CoV- Mpro inhibitors and (3) training of a classifier for bioactivity prediction using transfer learning. The fine-tuned chemical model generated > 90% valid, diverse and novel (not present on the training set) structures. The generated molecules showed a good overlap with Mpro chemical space, displaying similar physicochemical properties and chemical structures. In addition, novel scaffolds were also generated, showing the potential to explore new chemical series. The classification model outperformed the baseline area under the precision-recall curve, showing it can be used for prediction. In addition, the model also outperformed the freely available model Chemprop on an external test set of fragments screened against SARS-CoV-2 Mpro, showing its potential to identify putative antivirals to tackle the COVID-19 pandemic. Finally, among the top-20 predicted hits, we identified nine hits via molecular docking displaying binding poses and interactions similar to experimentally validated inhibitors.
A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
Authors: Bever Katherine M. , Thomas Dwayne L. , Zhang Jiajia , Diaz Rivera Ernie A. , Rosner Gary L. , Zhu Qingfeng , Nauroth Julie M. , Christmas Brian , Thompson Elizabeth D. , Anders Robert A. , Judkins Carol , Liu Meizheng , Jaffee Elizabeth M. , Ahuja Nita , Zheng Lei , Azad Nilofer S.
Published: February 2021

Epigenetic therapies may modulate the tumor microenvironment. We evaluated the safety and optimal sequence of combination DNA methyltransferase inhibitor guadecitabine with a granulocyte macrophage-colony-stimulating-factor (GM-CSF) secreting colon cancer (CRC) vaccine (GVAX) using a primary endpoint of change in CD45RO + T cells. 18 patients with advanced CRC enrolled, 11 underwent paired biopsies and were evaluable for the primary endpoint. No significant increase in CD45RO + cells was noted. Grade 3–4 toxicities were expected and manageable. Guadecitabine + GVAX was tolerable but demonstrated no significant immunologic activity in CRC. We report a novel trial design to efficiently evaluate investigational therapies with a primary pharmacodynamic endpoint.

Trial registry Clinicaltrials.gov: NCT01966289. Registered 21 October, 2013.
Characteristic pancreatic and splenic immune cell infiltration patterns in mouse acute pancreatitis
Authors: Yang Baibing , Davis Joy M. , Gomez Thomas H. , Younes Mamoun , Zhao Xiurong , Shen Qiang , Wang Run , Ko Tien C. , Cao Yanna
Published: February 2021

Background

A systemic evaluation of immune cell infiltration patterns in experimental acute pancreatitis (AP) is lacking. Using multi-dimensional flow cytometry, this study profiled infiltrating immune cell types in multiple AP mouse models.

Methods

Three AP models were generated in C57BL/6 mice via cerulein (CAE) injection, alcohol and palmitoleic acid (EtOH + POA) injection, and alcohol diet feeding and cerulein (EtOH + CAE) injection. Primary pancreatic cells and splenocytes were prepared, and multi-dimensional flow cytometry was performed and analyzed by manual gating and computerized PhenoGraph, followed by visualization with t-distributed stochastic neighbor embedding (t-SNE).

Results

CAE treatment induced a time-dependent increase of major innate immune cells and a decrease of follicular B cells, and TCD4+ cells and the subtypes in the pancreas, whereas elicited a reversed pattern in the spleen. EtOH + POA treatment resulted in weaker effects than CAE treatment. EtOH feeding enhanced CAE-induced amylase secretion, but unexpectedly attenuated CAE-induced immune cell regulation. In comparison with manual gating analysis, computerized analysis demonstrated a remarkable time efficiency and reproducibility on the innate immune cells and B cells.

Conclusions

The reverse pattern of increased innate and decreased adaptive immune cells was consistent in the pancreas in CAE and EtOH + POA treatments. Alcohol feeding opposed the CAE effect on immune cell regulation. Together, the immune profiling approach utilized in this study provides a better understanding of overall immune responses in AP, which may facilitate the identification of intervention windows and new therapeutic strategies. Computerized analysis is superior to manual gating by dramatically reducing analysis time.
Global concerns of dental and oral health workers during COVID-19 outbreak: a scope study on the concerns and the coping strategies
Authors: Bastani Peivand , Mohammadpour Mohammadtaghi , Ghanbarzadegan Arash , Kapellas Kostas , Do Loc Giang
Published: February 2021

Background

Dental and oral health workers have direct contact with respiratory aerosols of patients during procedures. This study aimed to determine the main concerns of dental and oral health workers globally during COVID-19 outbreaks and the coping strategies that help the resilience of dental and oral healthcare system.

Methods

This scoping study was conducted in August 2020. After adjusting the search strategy, a systematic search of five databases (PubMed, ISI Web of Science, Scopus, ProQuest and EMBASE) was conducted. Data was extracted using Microsoft Excel and the contents of retrieved articles were analysed through a qualitative thematic analysis applying MAX QDA10.

Results

Most articles were either editorial/letters to the editor/commentary formats (34%), or literature reviews (26%). About half of the articles belonged to three countries of Italy, China and the USA (each 16% and totally 48%). Thematic analysis of included papers led to the identification of four main global concerns and 19 sub-concerns. Economic, ethical, social and professional concerns are among dental and oral health concerns. Other results indicate on three main themes and 13 sub-themes as the coping strategies including patient management, infection control and virtual strategies.

Conclusion

Dental and oral health care workers have many concerns relating to COVID-19 including economic, ethical, social and professional factors. Resolution of concerns may involve enhancing coping strategies relating to patient management and infection control strategies as well as using new technologies for virtual contact with the patient without any risk of infection.
Monochromatic green light stimulation during incubation shortened the hatching time via pineal function in White Leghorn eggs
Authors: Wang Panlin , Sun Yanyan , Li Yunlei , Fan Jing , Zong Yunhe , Isa Adamu Mani , Shi Lei , Wang Yuanmei , Ni Aixin , Ge Pingzhuang , Jiang Linlin , Bian Shixiong , Ma Hui , Yuan Zhengdong , Liu Xiaolin , Chen Jilan
Published: February 2021

Background

Effect of monochromatic green light illumination on embryo development has been reported in chickens. The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during embryonic development. However, the involvement of pineal gland in the light transduction process remains to be elucidated. In the present study, we investigated the influence of monochromatic green light on hatching time and explored the possible mechanism via pineal function.

Results

A total of 600 eggs of White Leghorn (Shaver strain) were incubated under photoperiods of either 12 h of light and 12 h of darkness using monochromatic green light (12L:12D group) or 24 h of darkness (0L:24D group) for 18 d. Compared to 0L:24D group, the green light stimulation shortened the hatching time without extending the hatch window or impairing hatchability. The liver of embryos incubated in the 12L:12D light condition was heavier than those of the 0L:24D group on d 21 post incubation which may be linked to the observed increase in the serum concentration of insulin-like growth factor 1 (IGF-1); primary secretion of the liver. Histological structure analysis of pineal gland demonstrated that the light stimulation increased follicle area, wall thickness and lumen area on d 10 and d 12 post incubation. Rhythmic function analysis demonstrated that three clock related genes (brain and muscle ARNT-like-1,BMAL1; circadian locomotor output cycles kaput,CLOCK; and cryptochrome-1,CRY1) and a melatonin rate-limiting enzyme related gene (arylalkylamine N-acetyltransferase,AANAT) were rhythmically expressed in the pineal gland of the 12L:12D group, but not in the 0L:24D group. Simultaneously, the light stimulation also increased the concentration of melatonin (MT), which was linked to hepatocyte proliferation and IGF-1 secretion in previous studies.

Conclusions

The 12L:12D monochromatic green light stimulation during incubation shortened hatching time without impairing hatching performance. Pineal gland’s early histological development and maturation of its rhythmic function were accelerated by the light stimulation. It may be the key organ in the photo-endocrine axis that regulates embryo development, and the potential mechanism could be through enhanced secretion of MT in the 12L:12D group which promotes the secretion of IGF-1.
Vocational training choice from a regional perspective
Authors: Schuster Katja , Margarian Anne
Published: February 2021

Motivated by discussions of skill mismatches on local German vocational educational and training (VET) markets, this paper analyses how occupational segments of VET entry of individuals with lower and intermediate secondary school degree relate to local labor market characteristics. The econometric analysis applies data from a survey conducted with 9th graders within the German National Educational Panel Study (NEPS). Considering opportunity structures and the local competition for training positions, we find that the match between occupations' skill demands and individuals' abilities tends to be specifically close in diverse and competitive urban labor markets. In non-competitive peripheral labor markets, in contrast, graduates with lower school certificates seem to have a higher likelihood of entering VET in segments that are specifically attractive for graduates with upper secondary school degree. The results on the allocation of abilities and the weight of preferences under different labor market conditions have different welfare implications from an individual, regional and general economic perspective.
Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system
Authors: Farooqi Hafiz Muhammad Umer , Kang Bohye , Khalid Muhammad Asad Ullah , Salih Abdul Rahim Chethikkattuveli , Hyun Kinam , Park Sung Hyuk , Huh Dongeun , Choi Kyung Hyun
Published: February 2021

Hepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.
Echocardiographic myocardial strain analysis describes subclinical cardiac dysfunction after craniospinal irradiation in pediatric and young adult patients with central nervous system tumors
Authors: Martinez Hugo R. , Salloum Ralph , Wright Erin , Bueche Lauren , Khoury Philip R. , Tretter Justin T. , Ryan Thomas D.
Published: February 2021

Background

Craniospinal irradiation (CSI) is part of the treatment of central nervous system (CNS) tumors and is associated with cardiovascular disease in adults. Global myocardial strain analysis including longitudinal peak systolic strain (GLS), circumferential peak systolic strain (GCS), and radial peak systolic strain (GRS) can reveal subclinical cardiac dysfunction.

Methods

Retrospective, single-center study in patients managed with CSI vs. age-matched controls. Clinical data and echocardiography, including myocardial strain analysis, were collected at early (< 12 months) and late (≥ 12 months) time points after completion of CSI.

Results

Echocardiograms were available at 20 early and 34 late time points. Patients at the late time point were older (21.7 ± 10.4 vs. 13.3 ± 9.6 years) and further out from CSI (13.1 ± 8.8 vs. 0.2 ± 0.3 years). Standard echocardiographic parameters were normal for both groups. For early, CSI vs. control: GLS was − 16.8 ± 3.6% vs. -21.3 ± 4.0% (p = 0.0002), GCS was − 22.5 ± 5.2% vs. -21.3 ± 3.4% (p = 0.28), and GRS was 21.8 ± 11.0% vs. 26.9 ± 7.7% (p = 0.07). For late, CSI vs. control: GLS was − 16.2 ± 5.4% vs. -21.6 ± 3.7% (p < 0.0001), GCS was − 20.9 ± 6.8% vs. -21.9 ± 3.5% (p = 0.42), and GRS was 22.5 ± 10.0% vs. 27.3 ± 8.3% (p = 0.03). Radiation type (proton vs. photon), and radiation dose (< 30 Gy vs. ≥ 30 Gy) did not impact any parameter, although numbers were small.

Conclusions

Subclinical cardiac systolic dysfunction by GLS is present both early and late after CSI. These results argue for future studies to determine baseline cardiovascular status and the need for early initiation of longitudinal follow-up post CSI.
Identification of zinc-binding peptides in ADAM17-inhibiting whey protein hydrolysates using IMAC-Zn2+ coupled with shotgun peptidomics
Authors: Udechukwu M. Chinonye , Dang Chi , Udenigwe Chibuike C.
Published: February 2021

Food components possessing zinc ligands can be used to inhibit zinc-dependent enzymes. In this study, zinc-binding peptides were derived from whey protein hydrolysates, and their ultrafiltration (> 1 and < 1 kDa) fractions, produced with Esperase (WPH-Esp), Everlase and Savinase. Immobilized metal affinity chromatography (IMAC-Zn2+) increased the zinc-binding capacity of the peptide fraction (83%) when compared to WPH-Esp (23%) and its < 1 kDa fraction (40%). The increased zinc-binding capacity of the sample increased the inhibitory activity against the zinc-dependent “a disintegrin and metalloproteinase 17”. LC-MS/MS analysis using a shotgun peptidomics approach resulted in the identification of 24 peptides originating from bovine β-lactoglobulin, α-lactalbumin, serum albumin, β-casein, κ-casein, osteopontin-k, and folate receptor-α in the fraction. The identified peptides contained different combinations of the strong zinc-binding group of residues, His+Cys, Asp+Glu and Phe+Tyr, although Cys residues were absent in the sequences. In silico predictions showed that the IMAC-Zn2+ peptides were non-toxins. However, the peptides possessed poor drug-like and pharmacokinetic properties; this was possibly due to their long chain lengths (5–19 residues). Taken together, this work provided an array of food peptide-based zinc ligands for further investigation of structure-function relationships and development of nutraceuticals against inflammatory and other zinc-related diseases.

Graphical abstract
President's Page: Pillars and columns: Building our future together
Authors: Nessim Maurice
Published: February 2021

Pillars and columns, as architectural features, first came into common use in ancient Egypt as early as 2600 BC. Their purpose then, and now, was to provide essential and lasting support for important, massive structures. As pillars and columns became more visible and essential around the world, the words took on broader meanings. The word pillar is now used to describe “a person or idea regarded as reliably providing essential support for something.” A column can be defined as “a section of a magazine or newspaper devoted to a particular subject or written by a particular person.”
Memorial
Authors: Fitterman David , Jagodits Francis L. , Roth Jerry , Witherly Ken
Published: February 2021

• Victor F. Labson, 1952–2020

• Michael John Lewis, 1940–2020