bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative study regarding distance learning and the conventional face-to-face approach conducted problem-based learning tutorial during the COVID-19 pandemic
Authors: Foo Chi-chung , Cheung Billy , Chu Kent-man
Published: March 2021

Background

Educational pedagogies were modified during the COVID-19 pandemic to minimise interruption to teaching. One approach has been the distance learning problem-based learning (PBL) tutorial utilising the online peer-to-peer platform. The aim of this study was to compare the performance of students using distance learning PBL tutorials using with that of students utilising the conventional face-to-face approach.

Methods

This retrospective study was conducted in a single academic institution. We compared two groups of fourth-year medical students from the same class: one group used distance learning (DL); the other, the face-to-face (FF) method. We used students’ baseline performance at the preceding block for one-to-one propensity score matching. Students utilising the PBL tutorial were given grades by their tutors according to a standardised scoring system encompassing five key areas (score range: 0–10). The main outcome was a student’s total score (i.e., the sum of the scores from the five key areas, ranging from 0 to 50).

Result

We matched 62 students in each group. With four tutorials, there were 490 observations, with 245 in each group. The mean total score for the DL group was 37.5 ± 4.6, which was significantly lower than that of the FF group (39.0 ± 4.4, p < 0.001). We noted that students in the DL group had a significantly lower scores for all five areas of proficiency: participation, communication, preparation, critical thinking and group skills.

Conclusion

Findings of this study revealed that the performance of students utilising the DL PBL tutorials was lower than that of students participating in the conventional FF approach. Further studies are needed to ascertain the underlying cause.
‘They already operated like it was a crisis, because it always has been a crisis’: a qualitative exploration of the response of one homeless service in Scotland to the COVID-19 pandemic
Authors: Parkes Tessa , Carver Hannah , Masterton Wendy , Falzon Danilo , Dumbrell Josh , Grant Susan , Wilson Iain
Published: March 2021

Background

The COVID-19 pandemic has necessitated unprecedented changes in the way that services are delivered to individuals experiencing homelessness and problem substance use. Protecting those at high risk of infection/transmission, whilst addressing the multiple health and social needs of this group, is of utmost importance. The aim of this novel qualitative study was to document how one service in Scotland, the Wellbeing Centre run by The Salvation Army, adapted in response.

Methods

Care was taken to identify methods that did not create additional stress at this pressured time. Semi-structured interviews were conducted with Centre clients (n = 10, in-person and telephone) and staff (n = 5, telephone), and external professionals (n = 5, telephone), during April–August 2020. These were audio-recorded, fully transcribed, and analysed using Framework. Service documents were used to enhance contextual understanding. Analysis was informed by theories of psychologically informed environments and enabling environments.

Results

The start of the pandemic was a time of confusion, disruption, and isolation. Centre staff rapidly adapted methods of engagement to provide a range of comprehensive physical and emotional supports, to both existing and new clients, through telephone and online communication and, eventually, socially distanced in-person support. This involved balancing the risks of COVID-19 infection/transmission with the benefits of continuity of support to those highly vulnerable to a range of harms. Whilst the pandemic created many challenges, it also facilitated removal of barriers, particularly concerning provision of harm reduction services which had previously been severely constrained. Clients described the Centre as a ‘lifeline’, providing stability and safety during a period of profound disruption when other services closed their doors. Strong leadership, intensive team working, support/training for staff, a focus on relationships, and active use of client feedback, enabled responsive adaptation to fast-changing demands and the creation of a ‘culture of care’.

Conclusion

This study provides a unique insight into the pandemic by analysing the response of one homeless service during the height of the pandemic. We present a range of implications that have international relevance for those designing policies, and adapting front-line services, to proactively respond to COVID-19 and the continued public health crises of homelessness and drug-related deaths.
The effect of the WKYMVm peptide on promoting mBMSC secretion of exosomes to induce M2 macrophage polarization through the FPR2 pathway
Authors: Zhao Wenbo , Hu Junxian , He Qingyi
Published: March 2021

Background

When multicystic vesicles (precursors of exosomes) are formed in cells, there are two results. One is decomposition by lysosomes, and the other is the generation of exosomes that are transported out through the transmembrane. On the other hand, M2 macrophages promote the formation of local vascularization and provide necessary support for the repair of bone defects. To provide a new idea for the treatment of bone defects, the purpose of our study was to investigate the effect of WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2) peptide on the secretion of exosomes from murine bone marrow-derived MSCs (mBMSCs) and the effect of exosomes on the polarization of M2 macrophages.

Methods

The WKYMVm peptide was used to activate the formyl peptide receptor 2 (FPR2) pathway in mBMSCs. First, we used Cell Counting Kit-8 (CCK-8) to detect the cytotoxic effect of WKYMVm peptide on mBMSCs. Second, we used western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of interferon stimulated gene 15 (ISG15) and transcription factor EB (TFEB) in mBMSCs. Then, we detected lysosomal activity using a lysozyme activity assay kit. Third, we used an exosome extraction kit and western blotting to detect the content of exosomes secreted by mBMSCs. Fourth, we used immunofluorescence and western blotting to count the number of polarized M2 macrophages. Finally, we used an inhibitor to block miRNA-146 in exosomes secreted by mBMSCs and counted the number of polarized M2 macrophages.

Results

We first found that the WKYMVm peptide had no toxic effect on mBMSCs at a concentration of 1 μmol/L. Second, we found that when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs, ISG15 and TFEB expression was decreased, leading to increased secretion of exosomes. We also found that lysosomal activity was decreased when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs. Third, we demonstrated that exosomes secreted by mBMSCs promote the polarization of M2 macrophages. Moreover, all these effects can be blocked by the WRWWWW (WRW4, H-Trp-Arg-Trp-Trp-Trp-Trp-OH) peptide, an inhibitor of the FPR2 pathway. Finally, we confirmed the effect of miRNA-146 in exosomes secreted by mBMSCs on promoting the polarization of M2 macrophages.

Conclusion

Our findings demonstrated the potential value of the WKYMVm peptide in promoting the secretion of exosomes by mBMSCs and eventually leading to M2 macrophage polarization. We believe that our study could provide a research basis for the clinical treatment of bone defects.
Feasibility of structured light Plethysmography (SLP) in patients with coronavirus disease 2019 (COVID-19)
Authors: Simon Natalie , Hussain Azhar , Kolvekar Priyanka , Kolvekar Shyam
Published: March 2021

As a result of the COVID-19 pandemic, most institutions have changed the way patients are assessed or investigated. Using novel non-contact technology, it is possible to continuously monitor the lung function of peri-operative patients undergoing cardiothoracic procedures. Primarily, this results in increased patient surveillance, and therefore, safety. Many centres, globally, are starting to use structured light plethysmography (SLP) technology, providing a non-aerosol generating procedure in place of traditional spirometry. While more evidence is needed, our clinical usage; previous and on-going studies; demonstrate definite potential that SLP is a valuable tool.
Impact of novel coronavirus Disease-19 (COVID-19) pandemic in Italian pediatric emergency departments: a national survey
Authors:   SIMEUP research group, Talarico Valentina , Pinto Luciano , Marseglia Gian Luigi , Centonze Antonella , Cristofaro Concetta , Reina Rocco , Nocerino Agostino , Lubrano Riccardo , Zampogna Stefania
Published: March 2021

Background

Coronavirus Disease-19 (COVID-19) has rapidly become a pandemic emergency, distressing health systems in each affected country. Preparation strategies for managing this pandemic have been keys to face the COVID-19 surge all over the world and all levels of care.

Materials and Methods

During the epidemic, the Italian society of pediatric emergency-urgency (SIMEUP) promoted a national survey aiming to evaluate preparedness and response of pediatric emergency departments (PED) critical in ensuring optimal management of COVID-19 cases.

Results

Our results suggest that Italian PED have promptly set a proactive approach to the present emergency. 98.9% of the hospitals have defined special pathways and assistive protocols concerning the management of pediatric COVID-19 cases. The highest percentage of application of the measures for preventive and protective for COVID-19 concerned the use of personal protective equipments.

Conclusions

Results show that the following measures for pediatric patients, admitted in PED, have been promptly implemented throughout the whole country: eg. use of protective devices, pre-triage of patients accessing the hospital. Despite COVID-19 being a new threat, we have shown that by developing an easy-to-follow decision algorithm and clear plans for the interventional platform teams, we can ensure optimal health care workers and patients’ safety.
On innovations of n-dimensional integral-type inequality on time scales
Authors: Akın Lütfi
Published: March 2021

Integral-type inequalities and dynamic equations have an important place in time scales. In this paper, we present some innovations of n-dimensional Minkowski’s integral-type inequality on time scales via $\lozenge _{\alpha } $

◊
α

-integral.
The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial
Authors: Ghorbani Zeinab , Rafiee Pegah , Haghighi Samaneh , Razeghi Jahromi Soodeh , Djalali Mahmoud , Moradi-Tabriz Hedieh , Mahmoudi Maryam , Togha Mansoureh
Published: March 2021

Background

Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients.

Methods and materials

Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-β) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method.

Results

Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-β was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-β (r = − 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study.

Conclusion

Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended.

Trial registration

The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 (https://www.irct.ir/trial/31246).
Impact of communication time delays on combined LFC and AVR of a multi-area hybrid system with IPFC-RFBs coordinated control strategy
Authors: Kalyan C H. Naga Sai , Rao G. Sambasiva
Published: March 2021

In this paper, the impact of communication time delays (CTDs) on combined load frequency control (LFC) and automatic voltage regulation (AVR) of a multi-area system with hybrid generation units is addressed. Investigation reveals that CTDs have significant effect on system performance. A classical PID controller is employed as a secondary regulator and its parametric gains are optimized with a differential evolution - artificial electric field algorithm (DE-AEFA). The superior performance of the presented algorithm is established by comparing with various optimization algorithms reported in the literature. The investigation is further extended to integration of redox flow batteries (RFBs) and interline power flow controller (IPFC) with tie-lines. Analysis reveals that IPFC and RFBs coordinated control enhances system dynamic performance. Finally, the robustness of the proposed control methodology is validated by sensitivity analysis during wide variations of system parameters and load.
Association of epileptiform brain activity and specific language impairment (SLI) in preschool children
Authors: Esmael Ahmed , Elsherbeny Sara , Abbas Mohammed
Published: March 2021

Background

Epileptiform activities can cause transient or permanent deficits that affect the children during development and may be accompanied by neurodevelopmental disorders like specific language impairment.

Objectives

The objective of this study was to find if there is a possible association and the impact of epilepsy and epileptiform activity in children with specific language impairment.

Patients and methods

The study was conducted on 80 children suffering from specific language impairment and 80 age and sex match healthy control children. Computed tomography brain was performed and electroencephalography was recorded for children. Intelligence quotient level, cognitive age, social, and phoniatric assessment were done for all patients.

Results

Eighty children with specific language impairment (51 males and 29 females) with a mean age of 4.11 ± 1.93. Patients with specific language impairment showed significantly higher rates of abnormal electroencephalography (P= 0.006) and epilepsy (P< 0.001) compared to the control group. Spearman correlation demonstrated a highly negative significant relationship linking the language, intelligence quotient with abnormal electroencephalography and epilepsy (r= − 0.91,P< 0.01 andr= − 0.91,P< 0.01 respectively). Also, there was a moderately inverse significant relationship linking the cognitive age, social with abnormal electroencephalography, and epilepsy (r =− 0.70,P< 0.05 andr= − 0.65,P< 0.05 respectively).

Conclusion

Epileptiform activities even without epilepsy in preschool children may alter normal language function. Specific language impairment was associated with lower intelligence quotient levels, social, and cognitive age.

Trial registration

ClinicalTrials.gov ID:NCT04141332
Does contrast-enhanced mammography have an impact on the detection of cancer in patients with risk of developing breast cancer?
Authors: Hashem Lamiaa Mohamed Bassam , Abd El Hamid Nancy Osama , Kamal Rasha Mohamed , Mansour Sahar Mahmoud , Lasheen Shaimaa , Tohamey Yasmin Mounir
Published: March 2021

Background

Contrast-enhanced mammography (CEM) has been discovered to be more sensitive and specific than two-dimensional full-field digital mammography (FFDM) in both screening and diagnostic settings. The aim of the study was to assess the additive role of CEM in the detection and characterization of breast lesions in women with increased risk of developing breast cancer. This prospective study included 283 female patients with increased risk of developing breast cancer (i.e., positive family history of breast cancer, personal history of breast cancer, and heterogeneously dense mammary parenchyma) coming for either screening (n = 127/283 (49.1%)) or diagnostic (n = 156/283 (55.1%)) purpose. All patients had FFDM and CEM done, and the findings were evaluated independently; final Breast Imaging Reporting And Data System (BIRADS) classification was given for each modality. Results were then compared with histopathology or ultrasound findings with routine follow-up for normal and typically benign findings.

Results

In this study, 283 women with mean age of 48 were enrolled. Among the studied cases regardless to a specific risk factor, 15/283 (5.3%) were diagnosed as normal, 13/283 (4.6%) as inflammatory lesions, 72/283(25.4%) as benign lesions, 6/283 (2.1%) as benign precancerous lesions, and 177/283 (62.5%) as malignant. The overall sensitivity and specificity of the CEM were 92.7 and 71.43 %, respectively, while FFDM were 80.90 and 59.05%, respectively.

Conclusion

Contrast-enhanced mammography is a valuable screening and diagnostic imaging modality in patients with increased risk of developing breast cancer with diagnostic indices higher than mammography resulting in a significantly higher cancer detection rate.
Insights on recent approaches in drug discovery strategies and untapped drug targets against drug resistance
Authors: Peraman Ramalingam , Sure Sathish Kumar , Dusthackeer V. N. Azger , Chilamakuru Naresh Babu , Yiragamreddy Padmanabha Reddy , Pokuri Chiranjeevi , Kutagulla Vinay Kumar , Chinni Santhivardhan
Published: March 2021

Background

Despite the various strategies undertaken in the clinical practice, the mortality rate due to antibiotic-resistant microbes has been markedly increasing worldwide. In addition to multidrug-resistant (MDR) microbes, the “ESKAPE” bacteria are also emerging. Of course, the infection caused by ESKAPE cannot be treated even with lethal doses of antibiotics. Now, the drug resistance is also more prevalent in antiviral, anticancer, antimalarial and antifungal chemotherapies.

Main body

To date, in the literature, the quantum of research reported on the discovery strategies for new antibiotics is remarkable but the milestone is still far away. Considering the need of the updated strategies and drug discovery approaches in the area of drug resistance among researchers, in this communication, we consolidated the insights pertaining to new drug development against drug-resistant microbes. It includes drug discovery void, gene paradox, transposon mutagenesis, vitamin biosynthesis inhibition, use of non-conventional media, host model, target through quorum sensing, genomic-chemical network, synthetic viability to targets, chemical versus biological space, combinational approach, photosensitization, antimicrobial peptides and transcriptome profiling. Furthermore, we optimally briefed about antievolution drugs, nanotheranostics and antimicrobial adjuvants and then followed by twelve selected new feasible drug targets for new drug design against drug resistance. Finally, we have also tabulated the chemical structures of potent molecules against antimicrobial resistance.

Conclusion

It is highly recommended to execute the anti-drug resistance research as integrated approach where both molecular and genetic research needs to be as integrative objective of drug discovery. This is time to accelerate new drug discovery research with advanced genetic approaches instead of conventional blind screening.
Terahertz radiation generation from short-pulse laser interaction with electron-hole plasmas
Authors: Gurjar M. C. , Gopal K. , Gupta D. N. , Kulagin V. V.
Published: March 2021

In semiconductors, electrons and their corresponding holes exist as free carriers that are created in pairs in inter-band transitions. At very high carrier densities, the carrier-carrier collisions dominate over carrier-lattice collisions and these carriers begin to behave collectively to form a plasma. In this study, we present phase-matched terahertz (THz) radiation generation from laser interaction with electron-hole plasmas. Two collinear laser pulses of finite spot size propagate in an electron-hole plasma to generate THz radiation. The lasers beat and exert a ponderomotive force on electrons and holes. The carriers oscillate with oscillatory velocity at the laser beat frequency. The laser beat wave interacts with the plasma density perturbation and produces a nonlinear transverse current with nonzero curl. This nonlinear current drives coherent THz radiation. Spacial density modulation of hole density is considered to satisfy the phase-matching condition for resonant interaction. The systematic analysis of this mechanism shows an efficient and tunable source of THz radiation, which varies with various parameters such as the density modulation, laser intensity and other laser parameters.
A Clinical Review of Slipping Rib Syndrome
Authors: Foley Davelaar Cassidy M.
Published: March 2021

Slipping rib syndrome is pain created at the lower, anterior border of the rib cage when performing upper-extremity activities, coughing, laughing, or leaning over. Defects in the costal cartilage of ribs 8 to 10 result in increased movement of the ribs, impinging soft tissue and intercostal nerves. Advancements have been made in the diagnosis of slipping rib syndrome by dynamic ultrasound. Ultrasound can identify abnormalities in the rib and cartilage anatomy, as well as soft tissue swelling. Although the mainstays of treatment continue to be reassurance, nonsteroidal anti-inflammatory drugs, physical therapy, intercostal nerve injections, osteopathic manipulative treatment, surgery for refractory pain, and botulinum toxin injections have been attempted, and there may be a role for prolotherapy in treatment. Surgical techniques are being examined secondary to recurrence of pain following resection. The hooking maneuver and surgery remain important for identification and treatment, respectively.
Clinical Practice Guidelines for Exertional Rhabdomyolysis: A Military Medicine Perspective
Authors: Nye Nathaniel S. , Kasper Korey , Madsen Clifford Marc , Szczepanik Michelle , Covey Carlton J. , Oh Robert , Kane Shawn , Beutler Anthony I. , Leggit Jeffrey C. , Deuster Patricia A. , O'Connor Francis G.
Published: March 2021

Exertional rhabdomyolysis (ER) is an uncommon condition with a paucity of evidence-based guidance for diagnosis, management, and return to duty or play. Recently, a clinical practice guideline for diagnosis and management of ER in warfighters was updated by a team of military and civilian physicians and researchers using current scientific literature and decades of experience within the military population. The revision concentrated on challenging and controversial clinical questions with applicability to providers in the military and those in the greater sports medicine community. Specific topics addressed: 1) diagnostic criteria for ER; 2) clinical decision making for outpatient versus inpatient treatment; 3) optimal strategies for inpatient management; 4) discharge criteria; 5) identification and assessment of warfighters/athletes at risk for recurrent ER; 6) an appropriate rehabilitative plan; and finally, 7) key clinical questions warranting future research.
Las prácticas funerarias de la Edad del Bronce en la provincia de Málaga (España)
Authors: Aranda Jiménez Gonzalo
Published: March 2021

Las prácticas funerarias de la Edad del Bronce en Málaga se caracterizan por la continuidad y reutilización de sepulturas colectivas y por la innovación que supuso la aparición de las necrópolis de cistas asociadas a enterramientos individuales. La persistencia en el uso de tumbas megalíticas y cuevas artificiales no sólo quedaría atestiguada por ajuares funerarios y dataciones radiocarbónicas de la Edad del Bronce sino también por la continuidad en la construcción de nuevos espacios de enterramiento colectivo, especialmente hipogeos. Frente a la relevancia de este fenómeno, la aparición de las sepulturas en cistas habría tenido una trascendencia social muy limitada, o al menos así parece desprenderse del exiguo consumo de objetos de alto valor social, como los adornos realizados en plata. Esto indicaría que los comportamientos sociales colectivos tendrán una mayor pervivencia frente a las tendencias de individualización propias del Bronce.
The masked crusader
Authors: Wedlake Corey
Published: March 2021

Corey Wedlake is an apprentice dental nurse by day and a retained firefighter by night – and at weekends. Here, he talks about compassionate care in both his guises
Integration time optimization and starting angle autocalibration of full Stokes imagers based on a rotating retarder
Authors: Li Xiaobo , Goudail François , Qi Pengfei , Liu Tiegen , Hu Haofeng
Published: March 2021

Full Stokes imaging can be performed with a continuously rotating retarder in front of a fixed polarizer and a standard camera (RRFP) or a division of a focal plane polarization camera (RRDOFP). We determine the optimal number and duration of intensity measurements through a cycle of the retarder for these two types of setups as a function of instrument and noise parameters. We show that this number mainly depends on the type of noise that corrupts the measurements. We also show that with these setups, the starting angle of the retarder need not be known precisely and can be autocalibrated, which facilitates synchronization of the rotating retarder with the camera. We investigate the precision and feasibility domain of this autocalibration and show the RRDOFP setup has more attractive properties compared with RRFP setup. These results are important to optimize and facilitate the operation of polarization imagers based on a rotating retarder.
Focus calibration method based on the illumination beam scanning angle modulation in a grating alignment system
Authors: Zhang Tao , Ma Yarui , Li Jiean , Sun Tao , Zhao Xingyu , Cui Jiwen
Published: March 2021

A focus calibration method is developed to determine the focus position of a grating alignment system. An illumination beam scanning module is utilized to generate a circular motion for the beam, which forms an angular modulation interference image on the reference mark. A theoretical model is presented to determine the focus by determining the alignment grating z-position, at which the alignment offset is independent of the incident beam tilt. The standard uncertainty of the focus calibration results is estimated to be better than 150 nm. This technique may improve the measurement performance for lithography systems and precision machine applications.
Optical incoherent synthetic aperture imaging by superposition of phase-shifted optical transfer functions
Authors: Rai Mani Ratnam , Rosen Joseph
Published: March 2021

The concept of an optical incoherent synthetic aperture is widely used in astronomical interferometric telescopes. In this Letter, we propose a new, to the best of our knowledge, method to realize optical incoherent synthetic aperture imaging. The method is based on a superposition of optical transfer functions of incoherent imaging systems. Only two small sub-apertures, out of a much larger full synthetic aperture, are open at any given time, and they transfer light from the observed object to the image sensor. During the imaging process, the two sub-apertures move over the full synthetic aperture, where the gap between them starts from zero and grows with time. For every position of the pair of sub-apertures, two images are captured. In one of the images, the sub-apertures have the same phase value, and in the other image, one of the sub-apertures is phase shifted by

π

radian relative to the other one. The final image with the image resolution of the synthetic aperture is obtained as a superposition of the entire recorded images. Optical experiments are performed on reflective objects, and results of the synthetic aperture-based method demonstrate an imaging performance similar to that of direct imaging by a system with a single aperture of the size of the synthetic aperture.
MITOL-dependent ubiquitylation negatively regulates the entry of PolγA into mitochondria
Authors: Hussain Mansoor , Mohammed Aftab , Saifi Shabnam , Khan Aamir , Kaur Ekjot , Priya Swati , Agarwal Himanshi , Sengupta Sagar
Published: March 2021

Mutations in mitochondrial replicative polymerase PolγA lead to progressive external ophthalmoplegia (PEO). While PolγA is the known central player in mitochondrial DNA (mtDNA) replication, it is unknown whether a regulatory process exists on the mitochondrial outer membrane which controlled its entry into the mitochondria. We now demonstrate that PolγA is ubiquitylated by mitochondrial E3 ligase, MITOL (or MARCH5, RNF153). Ubiquitylation in wild-type (WT) PolγA occurs at Lysine 1060 residue via K6 linkage. Ubiquitylation of PolγA negatively regulates its binding to Tom20 and thereby its mitochondrial entry. While screening different PEO patients for mitochondrial entry, we found that a subset of the PolγA mutants is hyperubiquitylated by MITOL and interact less with Tom20. These PolγA variants cannot enter into mitochondria, instead becomes enriched in the insoluble fraction and undergo enhanced degradation. Hence, mtDNA replication, as observed via BrdU incorporation into the mtDNA, was compromised in these PEO mutants. However, by manipulating their ubiquitylation status by 2 independent techniques, these PEO mutants were reactivated, which allowed the incorporation of BrdU into mtDNA. Thus, regulated entry of non-ubiquitylated PolγA may have beneficial consequences for certain PEO patients.
Bridging the gap: Using reservoir ecology and human serosurveys to estimate Lassa virus spillover in West Africa
Authors: Basinski Andrew J. , Fichet-Calvet Elisabeth , Sjodin Anna R. , Varrelman Tanner J. , Remien Christopher H. , Layman Nathan C. , Bird Brian H. , Wolking David J. , Monagin Corina , Ghersi Bruno M. , Barry Peter A. , Jarvis Michael A. , Gessler Paul E. , Nuismer Scott L.
Published: March 2021

Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies. An important weakness of existing approaches, however, is that they generally rely on combining human and reservoir infection data during the training process and thus conflate risk attributable to the prevalence of the pathogen in the reservoir population with the risk attributed to the realized rate of spillover into the human population. Because effective planning of interventions requires that these components of risk be disentangled, we developed a multi-layer machine learning framework that separates these processes. Our approach begins by training models to predict the geographic range of the primary reservoir and the subset of this range in which the pathogen occurs. The spillover risk predicted by the product of these reservoir specific models is then fit to data on realized patterns of historical spillover into the human population. The result is a geographically specific spillover risk forecast that can be easily decomposed and used to guide effective intervention. Applying our method to Lassa virus, a zoonotic pathogen that regularly spills over into the human population across West Africa, results in a model that explains a modest but statistically significant portion of geographic variation in historical patterns of spillover. When combined with a mechanistic mathematical model of infection dynamics, our spillover risk model predicts that 897,700 humans are infected by Lassa virus each year across West Africa, with Nigeria accounting for more than half of these human infections.
Analyses of cancer incidence and other morbidities in neutron irradiated B6CF1 mice
Authors: Zander Alia , Paunesku Tatjana , Woloschak Gayle E.
Published: March 2021

The Department of Energy conduced ten large-scale neutron irradiation experiments at Argonne National Laboratory between 1972 and 1989. Using a new approach to utilize experimental controls to determine whether a cross comparison between experiments was appropriate, we amalgamated data on neutron exposures to discover that fractionation significantly improved overall survival. A more detailed investigation showed that fractionation only had a significant impact on the death hazard for animals that died from solid tumors, but did not significantly impact any other causes of death. Additionally, we compared the effects of sex, age first irradiated, and radiation fractionation on neutron irradiated mice versus cobalt 60 gamma irradiated mice and found that solid tumors were the most common cause of death in neutron irradiated mice, while lymphomas were the dominant cause of death in gamma irradiated mice. Most animals in this study were irradiated before 150 days of age but a subset of mice was first exposed to gamma or neutron irradiation over 500 days of age. Advanced age played a significant role in decreasing the death hazard for neutron irradiated mice, but not for gamma irradiated mice. Mice that were 500 days old before their first exposures to neutrons began dying later than both sham irradiated or gamma irradiated mice.
Patient factors and outcomes associated with discordance between quantitative and qualitative cardiac PET ischemia information
Authors: Zigray Haley , Elman Shana , Cheng Richard K. , Li Song , Lee James , Soine Laurie , Caldwell James , Alessio Adam M.
Published: March 2021

Background

Cardiac PET can provide quantitative myocardial blood flow (MBF) estimates. The frequency and clinical significance of discordant ischemia information between quantitative and qualitative parameters is unclear.

Methods

This retrospective, cohort study analyzed 256 Rb-82 stress-rest PET/CT studies. Global MBF and myocardial flow reserve (MFR) were estimated in absolute units for quantitative results and sum-stress and difference scores were used for qualitative results. Four groups of patients were evaluated based on a specific definition of concordant and discordant quantitative and qualitative results.

Results

31% of cases demonstrated discordance. Factors associated with microvascular disease were more common in the groups with abnormal quantitative results, regardless of the qualitative findings. Patients with concordant abnormal results had a significantly increased risk of myocardial infarction, heart failure, percutaneous intervention, and all-cause-mortality at 1 year compared to patients with concordant normal results. In patients with discordant results of abnormal quantitative and normal qualitative findings, there was a higher prevalence of heart failure than in controls (12.5% vs 0%, p = 0.01).

Conclusions

Discordance in qualitative and quantitative ischemia measures from PET is common, and further study is needed to clarify its prognostic implications. Moreover, quantitative estimation of MBF and MFR appears to add value to qualitative visual interpretation by supporting qualitative findings when results are concordant. Abnormal quantitative findings, regardless of concordance or discordance with qualitative findings, occurred in patients with risk factors associated with diffuse disease and with increased risk of heart failure admission.
STI prevalence among men living with HIV engaged in safer conception care in rural, southwestern Uganda
Authors: Chitneni Pooja , Bwana Mwebesa Bosco , Muyindike Winnie , Owembabazi Moran , Kalyebara Paul Kato , Byamukama Adolf , Mbalibulha Yona , Smith Patricia M. , Hsu Katherine K. , Haberer Jessica E. , Kaida Angela , Matthews Lynn T.
Published: March 2021

HIV care provides an opportunity to integrate comprehensive sexual and reproductive healthcare, including sexually transmitted infection (STI) management. We describe STI prevalence and correlates among men living with HIV (MLWH) accessing safer conception care to conceive a child with an HIV-uninfected partner while minimizing HIV transmission risks. This study reflects an ongoing safer conception program embedded within a regional referral hospital HIV clinic in southwestern Uganda. We enrolled MLWH, planning for pregnancy with an HIV-uninfected partner and accessing safer conception care. Participants completed interviewer-administered questionnaires detailing socio-demographics, gender dynamics, and sexual history. Participants also completed STI laboratory screening for syphilis (immunochromatographic testing confirmed by rapid plasma reagin), and chlamydia, gonorrhea, trichomoniasis, and HIV-RNA via GeneXpert nucleic acid amplification testing. Bivariable associations of STI covariates were assessed using Fisher’s exact test. Among the 50 men who completed STI screening, median age was 33 (IQR 31–37) years, 13/50 (26%) had ≥2 sexual partners in the prior three months, and 46/50 (92%) had HIV-RNA <400 copies/mL. Overall, 11/50 (22%) had STIs: 16% active syphilis, 6% chlamydia. All participants initiated STI treatment. STI prevalence was associated with the use of threats/intimidation to coerce partners into sex (27% vs 3%; p = 0.03), although absolute numbers were small. We describe a 22% curable STI prevalence among a priority population at higher risk for transmission to partners and neonates. STI screening and treatment as a part of comprehensive sexual and reproductive healthcare should be integrated into HIV care to maximize the health of men, women, and children.
Evaluation of a new culture medium for isolation of nontuberculous mycobacteria from environmental water samples
Authors: Alexander Kimberly J. , Furlong Jennifer L. , Baron Julianne L. , Rihs John D. , Stephenson Dominic , Perry John D. , Stout Janet E.
Published: March 2021

Nontuberculous mycobacteria (NTM) are waterborne pathogens commonly found in building water systems where they are a primary concern to vulnerable patient populations and can cause severe disease. The recovery of NTM from environmental samples can be a laborious undertaking and current pre-treatment methods and selective media lack sensitivity. We explored the use of the highly selective Rapidly Growing Mycobacteria (RGM) medium for culturing NTM from environmental water samples compared to existing methods. In total, 223 environmental water samples, including potable and non-potable water, were cultured for NTM using three culture media. In addition to direct culture on RGM medium, each sample was cultured on Middlebrook 7H10 medium and Mitchison 7H11 medium after pre-treatment with 0.2M KCl-HCl. Additionally, 33 distinct species of NTM were inoculated onto RGM medium and 7H10 medium in parallel to directly compare their growth. The use of RGM medium alone without pre-treatment provided a sensitivity (91%) comparable to that offered by culture on both 7H10 and 7H11 with acid pretreatment (combined sensitivity; 86%) with significantly less overgrowth and interference from other organisms on RGM medium. The average concentration of NTM observed on RGM medium alone was comparable to or greater than the NTM concentration on either medium alone or combined. Thirty-three species were examined in parallel and all tested strains of 27 of these species successfully grew on RGM medium, including 19 of 21 from the CDC’s healthcare-associated infections species list. RGM medium was successful at recovering environmental NTM without a pre-treatment, greatly reducing labor and materials required to process samples. Simplification of culture processing for environmental NTM will allow for a better assessment of their presence in building water systems and the potential for reduced exposure of susceptible populations.
The Xpert® MTB/RIF diagnostic test for pulmonary and extrapulmonary tuberculosis in immunocompetent and immunocompromised patients: Benefits and experiences over 2 years in different clinical contexts
Authors: Tomaz Ana Paula de Oliveira , Raboni Sonia Mara , Kussen Gislene Maria Botão , da Silva Nogueira Keite , Lopes Ribeiro Clea Elisa , Costa Libera Maria Dalla
Published: March 2021

Xpert®MTB/RIF has been widely used for tuberculosis (TB) diagnosis in Brazil, since 2014. This prospective observational study aimed to evaluate the performance of Xpert in different contexts during a two-year period: (i) laboratory and clinical/epidemiological diagnosis; (ii) HIV-positive and -negative populations; (iii) type of specimens: pulmonary and extrapulmonary. Overall, 924 specimens from 743 patients were evaluated. The performance of the assays was evaluated considering culture (Lowenstein Jensen or LJ medium) results and composite reference standard (CRS) classification as gold standard. According to CRS evaluation, 219 cases (29.5%) were classified as positive cases, 157 (21.1%) as ‘possible TB’, and 367 (49.3%) as ‘not TB’. Based on culture, Xpert and AFB smear achieved a sensitivity of 96% and 62%, respectively, while based on CRS, the sensitivities of Xpert, AFB smear, and culture were 40.7%, 20%, and 25%, respectively. The pooled sensitivity and specificity of Xpert were 96% and 94%, respectively. Metric evaluations were similar between pulmonary and extrapulmonary samples against culture, whereas compared to CRS, the sensitivities were 44.6% and 29.3% for the pulmonary and extrapulmonary cases, respectively. The Xpert detected 42/69 (60.9%) patients with confirmed TB and negative culture on LJ medium, and 52/69 (75.4%) patients with negative AFB smear results. There was no significant difference in the diagnostic accuracy based on the types of specimens and population (positive- and negative-HIV). Molecular testing detected 13 cases of TB in culture-negative patients with severe immunosuppression. Resistance to rifampicin was detected in seven samples. Herein, Xpert showed improved detection of pulmonary and extrapulmonary TB cases, both among HIV-positive and -negative patients, even in cases with advanced immunosuppression, thereby performing better than multiple other diagnostic parameters.
Social factors associated with reversing frailty progression in community-dwelling late-stage elderly people: An observational study
Authors: Takatori Katsuhiko , Matsumoto Daisuke
Published: March 2021

Frailty is considered to be a complex concept based mainly on physical vulnerability, but also vulnerabilities in mental/psychological and social aspects. Frailty can be reversible with appropriate intervention; however, factors that are important in recovering from frailty have not been clarified. The aim of the present study was to identify factors that help an individual reverse frailty progression and characteristics of individuals that have recovered from frailty. Community-dwelling people aged ≥75 years who responded to the Kihon Checklist (KCL) were enrolled in the study. The KCL consists of 25 yes/no questions in 7 areas: daily-life related activities, motor functions, nutritional status, oral functions, homebound, cognitive functions, and depressed mood. The number of social activities, degree of trust in the community, degree of interaction with neighbors, and subjective age were also evaluated. Frailty was assessed based on the number of checked items: 0–3 for robust, 4–7 for pre-frailty, and ≥8 for frailty. A total of 5050 participants were included for statistical analysis. At the time of the baseline survey in 2016, 18.7% (n = 942) of respondents had frailty, and the follow-up survey showed that the recovery rate from frailty within 2 years (median 24 months) was 31.8% (n = 300). Multiple logistic regression analysis showed that exercise-based social participation (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.2–3.4; P<0.01) and self-rated health (OR 1.2, CI 1.0–1.5; P = 0.02) were related to reversing frailty progression. Principal component analysis indicated that the main factors constituting the first principal component (contribution rate, 18.3%) included items related to social capital, such as interaction with neighbors, trust in the community, and number of social participation activities. Our results demonstrate that exercise-based social participation and high self-rated health have associations with reversing frailty progression. Individuals that recovered from frailty are characterized by high individual-level social capital components (i.e., trust in community, interaction with neighbors, and social participation).
The smell of success: Reproductive success related to rub behavior in brown bears
Authors: Morehouse Andrea T. , Loosen Anne E. , Graves Tabitha A. , Boyce Mark S.
Published: March 2021

Several species of bears are known to rub deliberately against trees and other objects, but little is known about why bears rub. Patterns in rubbing behavior of male and female brown bears (Ursus arctos) suggest that scent marking via rubbing functions to communicate among potential mates or competitors. Using DNA from bear hairs collected from rub objects in southwestern Alberta from 2011–2014 and existing DNA datasets from Montana and southeastern British Columbia, we determined sex and individual identity of each bear detected. Using these data, we completed a parentage analysis. From the parentage analysis and detection data, we determined the number of offspring, mates, unique rub objects where an individual was detected, and sampling occasions during which an individual was detected for each brown bear identified through our sampling methods. Using a Poisson regression, we found a positive relationship between bear rubbing behavior and reproductive success; both male and female bears with a greater number of mates and a greater number of offspring were detected at more rub objects and during more occasions. Our results suggest a fitness component to bear rubbing, indicate that rubbing is adaptive, and provide insight into a poorly understood behaviour.