bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of plasma beta effects on the island divertor transport in the standard configuration of W7-X
Authors: Xu S. , Liang Y. , Knieps A. , Zhou S. , Feng Y. , Reiter D. , Suzuki Y. , Jia M. , Geiger J. , Reimold F. , König R. , Dinklage A. , Harting D. , Luo Y. , Drews P. , Jakubowski M. , Gao Y. , Pasch E. , Pandey A. , Langenberg A. , Pablant N. , Brezinsek S. , Wang E. , Liu S. , Xiang H.M. , Neubauer O. , Huang J. , Cai J. , Yang J. , Liu J. , Liao L. , Gao Y.C.
Published: March 2023

The influence of plasma beta effects on the edge plasma transport in the Wendelstein 7-X standard configuration is studied systematically by using EMC3-EIRENE combined with a 3D equilibrium code named HINT. The magnetic topology changes induced by plasma beta effects are significantly reflected in plasma transport behaviors and heat flux patterns on divertor targets. After validating the modeling strategy by comparisons with experimental data, the extended simulations for high performance plasmas show that the threshold separatrix density for accessing the power detachment is reduced in higher beta plasmas. Compared with the vacuum field case, the impurity radiation distributions with finite beta effects are modified in the magnetic island region. The divertor heat flux is distributed more evenly along the toroidal direction on the strike line at the vertical target. The strike line on the horizontal target moves towards the pumping gap with an increase in the plasma beta. In addition, the different pressure profiles with the same central beta also result in a modified heat flux pattern on the divertor targets.
A large facility for photosensors test at cryogenic temperature
Authors: Balmforth Z. , Basco A. , Boiano A. , Canci N. , de Asmundis R. , Di Capua F. , Fiorillo G. , Grauso G. , Matteucci G. , Pandalone A. , Sandford E. , Suvorov Y. , Tortone G. , Vanzanella A.
Published: March 2023

Current generation of detectors using noble gases in liquid phase for direct dark matter search and neutrino physics need large area photosensors. Silicon based photo-detectors are innovative light collecting devices and represent a successful technology in these research fields. The DarkSide collaboration started a dedicated development and customization of SiPM technology for its specific needs resulting in the design, production and assembly of large surface modules of 20 × 20 cm2 named Photo Detection Unit for the DarkSide-20k experiment. Production of a large number of such devices, as needed to cover about 20 m2 of active surface inside the DarkSide-20k detector, requires a robust testing and validation process. In order to match this requirement a dedicated test facility for photosensors was designed and commissioned at INFN-Naples laboratory. The first commissioning test was successfully performed in 2021. Since then a number of testing campaigns were performed. Detailed description of the facility is reported as well as results of some tests.
The CMAM facility for proton-therapy pre-clinical studies: biomaterial irradiation experiments
Authors: Viñals S. , García G. , Magro R. , Manso M.
Published: March 2023

CMAM is a multidisciplinary-oriented scientific facility based on the operation of a 5 MV tandem ion accelerator and a suite of six beamlines, along with complementary infrastructures and scientific tools. This work describes CMAM, highlighting some of the present and future collaborations and standing out radiobiology (in particular Proton-therapy) as a strategic research line with high societal relevance. Proton-therapy has been, since the last thirty years, an alternative to conventional radio-treatment to heal or control radio-resistant cancers or tumours near sensitive organs such as spinal cord or brain tumours. The research in this field has a multidisciplinary approach since biologist, chemists and physicist must work together to detangle the different effects that are produced by the radiation. Flexible facilities such as CMAM may play a very relevant role in order to develop further basic knowledge and as a training field for students to this type of investigation. As an example of this, a preliminary radiobiology experiment is briefly described, in which a non-alive material with a similar composition than a cell culture was used to see the effects of the radiation and it was developed the basic methodologies for dose delivery and proton range control. The experiment was also used as a training practice for students in the framework of the INFIERI school conducted at Universidad Autónoma de Madrid in Summer 2021.
Digital signal processing for neutron-gamma discrimination using a liquid scintillator detector
Authors: Biganeh A. , Azizi M. , Kakuee O. , Rafi-Kheiri H. , Sedaghati Boorkhani M. , Ghasemi B.
Published: March 2023

Digital signal processing has shown promise as a reliable approach for nuclear radiation spectroscopy. In this paper, the charge-to-digital conversion technique was applied to neutron-gamma discrimination. The method is based on the direct comparison of the charge at the fast and slow components of the anode signal of the scintillator detector. The performance of the technique was tested using experimental investigation by 252Cf source and D-D neutron generator. The minimum detectable energy for reasonable separation was found to be around 0.2 MeVee. The FOM of the discrimination parameter was maximized by the optimum selection of the charge integration parameters. Excellent discrimination between neutron and gamma signals was confirmed by the presented setup. The results confirmed that the presented technique can replace analog nuclear electronics conventionally uses for pulse shape discrimination.
Novel biochemical aspects of lugdulysin, a Staphylococcus lugdunensis metalloprotease that inhibits formation and disrupts protein biofilm of methicillin-resistant Staphylococcus aureus
Authors: Martinez Juan Pinheiro de Oliveira , Vazquez Leonardo , Takeyama Matheus Mikio , dos Santos Filho Tarcizio José , Cavalcante Fernanda Sampaio , Guimarães Lorrayne Cardoso , Pereira Eliezer Menezes , dos Santos Katia Regina Netto
Published: March 2023

Staphylococcus lugdunensis produces lugdulysin, a metalloprotease that may contribute to its virulence. This study aimed to evaluate the biochemical aspects of lugdulysin and investigate its effect on Staphylococcus aureus biofilms. The protease was isolated and characterized for its optimal pH and temperature, hydrolysis kinetics, and influence of metal cofactor supplementation. The protein structure was determined via homology modeling. The effect on S. aureus biofilms was assessed by the micromethod technique. The protease optimal pH and temperature were 7.0 and 37 °C, respectively. EDTA inhibited protease activity, confirming it as a metalloprotease. Lugdulysin activity was not recovered by divalent ion supplementation post-inhibition, and supplementation with divalent ions did not change enzymatic activity. The isolated enzyme was stable for up to 3 h. Lugdulysin significantly inhibited the formation and disrupted preestablished protein-matrix MRSA biofilm. This preliminary study indicates that lugdulysin has a potential role as a competition mechanism and/or modulation of staphylococcal biofilm.
Grandparental co-residence and grandchild survival: the role of resource competition in a pre-industrial population
Authors: Chapman Simon , Danielsbacka Mirkka , Tanskanen Antti O , Lahdenperä Mirkka , Pettay Jenni , Lummaa Virpi
Published: March 2023

Although grandparents are and have been important alloparents to their grandchildren, they are not necessarily only beneficial but can also compete with grandchildren over limited resources. Competition over parental care or other resources may exist especially if grandparents live in the same household with grandchildren and it can be dependent on grandchild age. By utilizing demographic data collected from historic population registers in Finland between 1761 and 1895 (study sample n = 4041) we investigate whether grandparents living in the same household with grandchildren are detrimental or beneficial for grandchild survival. Having a living but not co-residing grandmother or grandfather were both associated with better survival whereas having a co-resident grandfather was associated with lower chance to survive for infants (age < 1 year). Separating the effect between maternal and paternal grandparents and grandmothers and grandfathers revealed no differences in the effects between lineages. Negative effect of having a co-residing grandfather was not significant when grandfathers were separated for lineage specific models. These results implicate that accounting for the co-residence status and child’s age, grandparents were mostly beneficial when not co-residing with very young children and that having a co-residing grandfather at that age could be associated with lower chances to survive. Predictions made by grandmother hypothesis and resource competition both received support. The results presented here also offered comparison points to preindustrial and contemporary three-generational families.
Disrupted multi-scale topological organization of directed functional brain networks in patients with disorders of consciousness
Authors: Guo Yu , Cao Bolin , He Yanbin , Xie Qiuyou , Liang Qimei , Lan Yue , Zhang Mingxian , Qiu Yidan , Yu Ronghao , Huang Ruiwang
Published: March 2023

Disorders of consciousness are impaired states of consciousness caused by severe brain injuries. Previous resting-state functional magnetic resonance imaging studies have reported abnormal brain network properties at different topological scales in patients with disorders of consciousness by using graph theoretical analysis. However, it is still unclear how inter-regional directed propagation activities affect the topological organization of functional brain networks in patients with disorders of consciousness. To reveal the altered topological organization in patients with disorders of consciousness, we constructed whole-brain directed functional networks by combining functional connectivity analysis and time delay estimation. Then we performed graph theoretical analysis based on the directed functional brain networks at three topological scales, from the nodal scale, the resting-state network scale to the global scale. Finally, the canonical correlation analysis was used to determine the correlations between altered topological properties and clinical scores in patients with disorders of consciousness. At the nodal scale, we observed decreased in-degree and increased out-degree in the precuneus in patients with disorders of consciousness. At the resting-state network scale, the patients with disorders of consciousness showed reorganized motif patterns within the default mode network and between the default mode network and other resting-state networks. At the global scale, we found a lower global clustering coefficient in the patients with disorders of consciousness than in the controls. The results of the canonical correlation analysis showed that the abnormal degree and the disrupted motif were significantly correlated with the clinical scores of the patients with disorders of consciousness. Our findings showed that consciousness impairment can be revealed by abnormal directed connection patterns at multiple topological scales in the whole brain, and the disrupted directed connection patterns may serve as clinical biomarkers to assess the dysfunction of patients with disorders of consciousness.
Are existing validated severity scores for epidermolysis bullosa reflective of the burden of disease in patients with epidermolysis bullosa simplex?
Authors: Hunjan Manrup K , Bardhan Ajoy , Zuzarte Louise , Balacco Dario Leonardo , Harper Natasha , Heagerty Adrian
Published: March 2023

Our study demonstrates that severity scores do not correlate well with the impact that localized epidermolysis bullosa simplex (EBS) has on quality of life. There is a paucity of literature exploring correlations between disease severity and patient-reported outcome measures in EB. Both the Birmingham EB Severity (BEBS) score and EB Disease Activity and Severity Index (EBDASI) consist of weighted factors including body surface area, scalp, mucous membrane, nail and systemic involvement, as well as complications of longstanding disease such as cutaneous squamous cell carcinoma, which is more commonly seen in recessive dystrophic EB. Current scoring systems fail to account for the palmoplantar blistering and keratoderma which is the most significant source of morbidity in the EBS cohort.
Prediction of melanoma Breslow thickness using deep transfer learning algorithms
Authors: Hernández-Rodríguez Juan-Carlos , Durán-López Lourdes , Domínguez-Morales Juan P , Ortiz-Álvarez Juan , Conejo-Mir Julián , Pereyra-Rodriguez Jose-Juan
Published: March 2023

Background

The distinction between in situ melanoma (MIS) and invasive melanoma is challenging even for expert dermatologists. The use of pretrained convolutional neural networks (CNNs) as ancillary decision systems needs further research.

Aim

To develop, validate and compare three deep transfer learning (DTL) algorithms to predict MIS vs. invasive melanoma and melanoma with a Breslow thickness (BT) of < 0.8 mm vs. ≥ 0.8 mm.

Methods

A dataset of 1315 dermoscopic images of histopathologically confirmed melanomas was created from Virgen del Rocio University Hospital and open repositories of the International Skin Imaging Collaboration archive and Polesie S et al. (Dermatol Pract Concept 2021; 11:e2021079). The images were labelled as MIS or invasive melanoma and < 0.8 mm or ≥ 0.8 mm of BT. We conducted three trainings, and overall means for receiver operating characteristic (ROC) curves, sensitivity, specificity, positive and negative predictive value, and balanced diagnostic accuracy outcomes were evaluated on the test set with ResNetV2, EfficientNetB6 and InceptionV3. The results of 10 dermatologists were compared with the algorithms. Grad-CAM gradient maps were generated, highlighting relevant areas considered by the CNNs within the images.

Results

EfficientNetB6 achieved the highest diagnostic accuracy for the comparison between MIS vs. invasive melanoma (61%) and BT < 0.8 mm vs. ≥ 0.8 mm (75%). For the BT comparison, ResNetV2 with an area under the ROC curve of 0.76 and InceptionV3 with an area under the ROC curve of 0.75, outperformed the results obtained by the dermatologist group with an area under the ROC curve of 0.70.

Conclusion

EfficientNetB6 recorded the best prediction results, outperforming the dermatologists for the comparison of 0.8 mm of BT. DTL could be an ancillary aid to support dermatologists’ decisions in the near future.
Hidradenitis suppurativa should be recognized as a weight-related comorbidity in National Institute for Health and Care guidelines on managing obesity
Authors: Hussain Khawar , Khalil Nada , Patel Neil P
Published: March 2023

We propose hidradenitis suppurativa (HS) is added to the list of weight-related comorbidities in the new National Institute for Health and Care Excellence guideline on obesity. Effective obesity management in patients with HS could help reduce disease severity, pain and cardiovascular risk, and improve quality of life and the efficacy of biologic therapy. In addition, it could reduce the costs of HS-associated care (GP visits, hospital outpatient attendances, biologic drugs, inpatient admissions, elective and emergency surgery).
Mechanisms regulating the properties of inhibition-based gamma oscillations in primate prefrontal and parietal cortices
Authors: Gonzalez-Burgos Guillermo , Miyamae Takeaki , Reddy Nita , Dawkins Sidney , Chen Chloe , Hill Avyi , Enwright John , Ermentrout Bard , Lewis David A
Published: March 2023

In primates, the dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices are key nodes in the working memory network. The working memory-related gamma oscillations induced in these areas, predominantly in layer 3, exhibit higher frequency in DLPFC. Although these regional differences in oscillation frequency are likely essential for information transfer between DLPFC and PPC, the mechanisms underlying these differences remain poorly understood. We investigated, in rhesus monkey, the DLPFC and PPC layer 3 pyramidal neuron (L3PN) properties that might regulate oscillation frequency and assessed the effects of these properties simulating oscillations in computational models. We found that GABAAR-mediated synaptic inhibition synchronizes L3PNs in both areas, but analysis of GABAAR mRNA levels and inhibitory synaptic currents suggested similar mechanisms of inhibition-mediated synchrony in DLPFC and PPC. Basal dendrite spine density and AMPAR/NMDAR mRNA levels were higher in DLPFC L3PNs, whereas excitatory synaptic currents were similar between areas. Therefore, synaptically evoked excitation might be stronger in DLPFC L3PNs due to a greater quantity of synapses in basal dendrites, a main target of recurrent excitation. Simulations in computational networks showed that oscillation frequency and power increased with increasing recurrent excitation, suggesting a mechanism by which the DLPFC–PPC differences in oscillation properties are generated.
Interhemispheric differences of pyramidal cells in the primary motor cortices of schizophrenia patients investigated postmortem
Authors: Szocsics Péter , Papp Péter , Havas László , Lőke János , Maglóczky Zsófia
Published: March 2023

Motor disturbances are observed in schizophrenia patients, but the neuroanatomical background is unknown. Our aim was to investigate the pyramidal cells of the primary motor cortex (BA 4) in both hemispheres of postmortem control and schizophrenia subjects—8 subjects in each group—with 2.5–5.5 h postmortem interval. The density and size of the Sternberger monoclonal incorporated antibody 32 (SMI32)-immunostained pyramidal cells in layer 3 and 5 showed no change; however, the proportion of larger pyramidal cells is decreased in layer 5. Giant pyramidal neurons (Betz cells) were investigated distinctively with SMI32- and parvalbumin (PV) immunostainings. In the right hemisphere of schizophrenia subjects, the density of Betz cells was decreased and their PV-immunopositive perisomatic input showed impairment. Part of the Betz cells contained PV in both groups, but the proportion of PV-positive cells has declined with age. The rat model of antipsychotic treatment with haloperidol and olanzapine showed no differences in size and density of SMI32-immunopositive pyramidal cells. Our results suggest that motor impairment of schizophrenia patients may have a morphological basis involving the Betz cells in the right hemisphere. These alterations can have neurodevelopmental and neurodegenerative explanations, but antipsychotic treatment does not explain them.
The Impact of Confounders on Symptom–Endoscopic Discordances in Crohn’s Disease
Authors: Rajan Anjana , Pan Yushan , Mahtani Prerna , Niec Rachel , Longman Randy , Gerber Juliette , Lukin Dana , Scherl Ellen , Battat Robert
Published: March 2023

Background

Discordances between clinical and endoscopic Crohn’s disease (CD) activity indices negatively impact the utility of clinic visits and efficacy assessments in clinical trials. Bile acid diarrhea (BAD) and small intestinal bacterial overgrowth (SIBO) mimic CD symptoms. This study quantified the impact of BAD and SIBO on the relationship between clinical and endoscopic disease activity indices.

Methods

CD patients with 7α-hydroxy-4-cholesten-3-one (7C4) serum measurements and/or SIBO breath tests and matched clinical and endoscopic scores were included. Clinical remission (stool frequency [SF] ≤ 1 and abdominal pain score ≤ 1) rates were compared between those with and without (1) endoscopic remission, (2) BAD (7C4 > 55 ng/mL), and (3) SIBO.

Results

Of 295 CD patients, 219 had SIBO testing and 87 had 7C4 testing. Patients with elevated 7C4 had lower proportions with clinical remission (14% vs 40%, P = .007) and SF ≤ 1 (14% vs 42%, P = .004) compared to those with normal 7C4. In patients with normal 7C4, higher rates of clinical remission (65% vs 27%, P = .01) and SF ≤ 1 (71% vs 27%, P = .003) existed in patients with endoscopic remission compared to those without endoscopic remission. Conversely, among the entire 295 patient cohorts, nearly identical clinical remission rates existed between those with and without endoscopic remission (25% vs 24%, P = .8), and the Crohn’s Disease Patient-Reported Outcome-2 score was not accurate for predicting endoscopic remission (Area Under the Curve (AUC): 0.48; 95% CI, 0.42–0.55). SIBO status did not impact clinical remission rates (P = 1.0).

Conclusions

BAD, but not SIBO, contributed to symptom scores. A relationship between endoscopic inflammation and clinical remission rates only existed in patients without 7C4 elevations.
Genetic analyses identify brain structures related to cognitive impairment associated with elevated blood pressure
Authors: Siedlinski Mateusz , Carnevale Lorenzo , Xu Xiaoguang , Carnevale Daniela , Evangelou Evangelos , Caulfield Mark J , Maffia Pasquale , Wardlaw Joanna , Samani Nilesh J , Tomaszewski Maciej , Lembo Giuseppe , Holmes Michael V , Guzik Tomasz J
Published: March 2023

Background and aims

Observational studies have linked elevated blood pressure (BP) to impaired cognitive function. However, the functional and structural changes in the brain that mediate the relationship between BP elevation and cognitive impairment remain unknown. Using observational and genetic data from large consortia, this study aimed to identify brain structures potentially associated with BP values and cognitive function.

Methods and results

Data on BP were integrated with 3935 brain magnetic resonance imaging-derived phenotypes (IDPs) and cognitive function defined by fluid intelligence score. Observational analyses were performed in the UK Biobank and a prospective validation cohort. Mendelian randomisation (MR) analyses used genetic data derived from the UK Biobank, International Consortium for Blood Pressure, and COGENT consortium. Mendelian randomisation analysis identified a potentially adverse causal effect of higher systolic BP on cognitive function [−0.044 standard deviation (SD); 95% confidence interval (CI) −0.066, −0.021] with the MR estimate strengthening (−0.087 SD; 95% CI −0.132, −0.042), when further adjusted for diastolic BP. Mendelian randomisation analysis found 242, 168, and 68 IDPs showing significant (false discovery rate P < 0.05) association with systolic BP, diastolic BP, and pulse pressure, respectively. Most of these IDPs were inversely associated with cognitive function in observational analysis in the UK Biobank and showed concordant effects in the validation cohort. Mendelian randomisation analysis identified relationships between cognitive function and the nine of the systolic BP-associated IDPs, including the anterior thalamic radiation, anterior corona radiata, or external capsule.

Conclusion

Complementary MR and observational analyses identify brain structures associated with BP, which may be responsible for the adverse effects of hypertension on cognitive performance.
Time of onset of atrial fibrillation and atrial fibrillation progression data from the RACE V study
Authors: van de Lande Martijn E , Rama Rajiv S , Koldenhof Tim , Arita Vicente Artola , Nguyen Bao-Oanh , van Deutekom Colinda , Weberndorfer Vanessa , Crijns Harry J G M , Hemels Martin E W , Tieleman Robert G , de Melis Mirko , Schotten Ulrich , Linz Dominik , Van Gelder Isabelle C , Rienstra Michiel ,   for the RACE V Investigators
Published: March 2023

Aims

Atrial fibrillation (AF) progression is associated with adverse outcome, but the role of the circadian or diurnal pattern of AF onset remains unclear. We aim to assess the association between the time of onset of AF episodes with the clinical phenotype and AF progression in patients with self-terminating AF.

Methods and results

The Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodelling, and Vascular Destabilization in the Progression of AF study included patients with self-terminating AF who underwent extensive phenotyping at baseline and continuous rhythm monitoring with an implantable loop recorder (ILR). In this subanalysis, ILR data were used to assess the development of AF progression and the diurnal pattern of AF onset: predominant (>80%) nocturnal AF, predominant daytime AF, or mixed AF without a predominant diurnal AF pattern. The median follow-up was 2.2 (1.6–2.8) years. The median age was 66 (59–71) years, and 117 (42%) were women. Predominant nocturnal (n = 40) and daytime (n = 43) AF onset patients had less comorbidities compared to that of mixed (n = 195) AF patients (median 2 vs. 2 vs. 3, respectively, P = 0.012). Diabetes was more common in the mixed group (12% vs. 5% vs. 0%, respectively, P = 0.031), whilst obesity was more frequent in the nocturnal group (38% vs. 12% vs. 27%, respectively, P = 0.028). Progression rates in the nocturnal vs. daytime vs. mixed groups were 5% vs. 5% vs. 24%, respectively (P = 0.013 nocturnal vs. mixed and P = 0.008 daytime vs. mixed group, respectively).

Conclusion

In self-terminating AF, patients with either predominant nocturnal or daytime onset of AF episodes had less associated comorbidities and less AF progression compared to that of patients with mixed onset of AF.

Clinical trial registration

NCT02726698
Care Narratives by Annie Ernaux and Michael Rosen in the Light of the Covid-19 Pandemic
Authors: Tribout-Joseph Sarah
Published: March 2023

The Covid-19 pandemic has highlighted both the importance of care and a global crisis in care. Since its beginnings in the US in the 1980s as a feminist theory within virtue ethics, care ethics has emerged from the margins of the domestic sphere in the West to become a species theory and a force for radical societal change. Influenced by Joan Tronto’s work, Alexandre Gefen has integrated the approach into literary studies in France as an interventionist reading strategy, offering therapeutic benefits to the reader as well. In a new intersectional approach, I argue that reading literature through a care ethics model can improve lives. I compare literary testimonies on either side of the patient/carer divide, Annie Ernaux’s pre-Covid-19 care home narrative and Michael Rosen’s Covid-19 patient testimony, which, read together, expand the field of medical humanities to promote a relational reconception of society over individualist neoliberalism.
A deep learning-based automatic tool for measuring the lengths of linear scars: forensic applications
Authors: Zhou Jian , Zhou Zhilu , Chen Xinjian , Shi Fei , Xia Wentao
Published: March 2023

It is important to measure scars in forensic and clinical medicine. In practice, scars are mostly manually measured, and the results are diverse and influenced by various subjective factors. With the development of digital image technology and artificial intelligence, noncontact and automatic photogrammetry has been gradually used in some practical applications. In this article, we propose an automatic method for measuring the length of linear scars based on multiview stereo and deep learning, which combines the 3D reconstruction algorithm of structure from motion and the image segmentation algorithm based on a convolutional neural network. With a few pictures taken by a smart phone, automatic segmentation and measurement of scars can be realized. The reliability of the measurement was first demonstrated through simulation experiments on five artificial scars, giving errors of length <5%. Then, experiment results on 30 clinical scar samples showed that our measurements were in high agreement with manual measurements, with an average error of 3.69%. Our study demonstrates that the application of photogrammetry in scar measurement is effective and that the deep learning technique can realize the automation of scar measurement with high accuracy.
3-D body-wave tomography from the seismic ambient noise recorded by a dense array in the Dehdasht area, Iran
Authors: Riahi Ali , Shomali Zaher-Hossein , Obermann Anne , Kamayestani Ahmad
Published: March 2023

The strong attenuation of the thick sedimentary layers in the Dehdasht region, Iran, renders active seismic exploration surveys difficult. The imaging of the existent limestone reservoirs is limited to the shallow subsurface due to the strong attenuation of seismic waves. Here, we discuss a different approach to imaging the subsurface using body waves extracted from the cross-correlation of the seismic ambient wavefield. We discuss the technical challenges to extracting clear P-wave arrivals from the seismic ambient wavefield of a dense 3-component seismic array deployed in the Dehdasht basin. We invert the data for the 3-D P-wave velocity structure and compare the velocity model with results from the 2-D active seismic surveys in the area. The results show the potential of using body waves extracted from the seismic ambient wavefield for imaging purposes in highly attenuating areas.
Characterizing the implementation of performance management interventions in a primary health care system: a case study of the Salud Mesoamerica Initiative in El Salvador
Authors: Aranda L Esther , Arif Zainab , Innocenti Cinzia , Wahid Syed Shabab , Frehywot Seble , Munar Wolfgang
Published: March 2023

Performance management (PM) reforms have been introduced in health systems worldwide to improve accountability, transparency and learning. However, gaps in evidence exist regarding the ways in which PM contributes to organizational-level outcomes. Between 2015 and 2017, the government of El Salvador and the Salud Mesoamerica Initiative (SMI) introduced team-based PM interventions in the country’s primary health care (PHC) system including target setting, performance measurement, provision of feedback and in-kind incentives. The programme’s evaluation showed widespread improvements in performance for community outreach and service timeliness, quality and utilization. The current study characterizes how the implementation of team-based PM interventions by SMI implementers contributed to PHC system performance improvements. We used a descriptive, single-case study design informed by a programme theory (PT). Data sources included qualitative in-depth interviews and SMI programme documents. We interviewed the members of four PHC teams (n = 13), Ministry of Health (MOH) decision makers (n = 8) and SMI officials (n = 6). Coded data were summarized, and thematic analysis was employed to identify broader categories and patterns. The outcomes chain in the PT was refined based on empirical findings that revealed the convergence of two processes: (1) increased social interactions and relationships among implementers that enhanced communication and created opportunities for social learning and (2) cyclical performance monitoring that generated novel flows of information. These processes contributed to emergent outcomes including the uptake of performance information, altruistic behaviours in service delivery and organizational learning. Through time, the cyclical nature of PM appears to have led to the spread of these behaviours beyond the teams studied here, thus contributing to system-wide effects. Findings illustrate the social nature of implementation processes and describe plausible pathways through which lower-order implementation programme effects can contribute to higher-order changes in system performance.
Genome-Wide Association Studies of Diarrhea Frequency and Duration in the First Year of Life in Bangladeshi Infants
Authors: Munday Rebecca M , Haque Rashidul , Wojcik Genevieve L , Korpe Poonum , Nayak Uma , Kirkpatrick Beth D , Petri William A , Duggal Priya
Published: March 2023

Background

Diarrhea is the second leading cause of death in children under 5 years old worldwide. Known diarrhea risk factors include sanitation, water sources, and pathogens but do not fully explain the heterogeneity in frequency and duration of diarrhea in young children. We evaluated the role of host genetics in diarrhea.

Methods

Using 3 well-characterized birth cohorts from an impoverished area of Dhaka, Bangladesh, we compared infants with no diarrhea in the first year of life to those with an abundance, measured by either frequency or duration. We performed a genome-wide association analysis for each cohort under an additive model and then meta-analyzed across the studies.

Results

For diarrhea frequency, we identified 2 genome-wide significant loci associated with not having any diarrhea, on chromosome 21 within the noncoding RNA AP000959 (C allele odds ratio [OR] = 0.31, P = 4.01 × 10−8), and on chromosome 8 within SAMD12 (T allele OR = 0.35, P = 4.74 × 10−7). For duration of diarrhea, we identified 2 loci associated with no diarrhea, including the same locus on chromosome 21 (C allele OR = 0.31, P = 1.59 × 10−8) and another locus on chromosome 17 near WSCD1 (C allele OR = 0.35, P = 1.09 × 10−7).

Conclusions

These loci are in or near genes involved in enteric nervous system development and intestinal inflammation and may be potential targets for diarrhea therapeutics.
The Relationship Between SARS-CoV-2 Neutralizing Antibody Titers and Avidity in Plasma Collected From Convalescent Nonvaccinated and Vaccinated Blood Donors
Authors: Nurmi Visa , Knight Chanice , Estcourt Lise , Hepojoki Jussi , Lamikanra Abigail A , Tsang Hoi P , Roberts David J , Polack Fernando P , Simmonds Peter , Hedman Klaus , Alvarez-Paggi Damian , Harvala Heli
Published: March 2023

Convalescent plasma (CP) treatment of coronavirus disease 2019 (COVID-19) has shown significant therapeutic effect when administered early (eg, Argentinian trial showing reduced hospitalization) but has in general been ineffective (eg, REMAP-CAP trial without improvement during hospitalization). To investigate whether the differences in CP used could explain the different outcomes, we compared neutralizing antibodies, anti-spike IgG, and avidity of CP used in the REMAP-CAP and Argentinian trials and in convalescent vaccinees. We found no difference between the trial plasmas, emphasizing initial patient serostatus as treatment efficacy predictor. By contrast, vaccinee CP showed significantly higher titers and avidity, being preferable for future CP treatment.

Clinical Trials Registration. NCT02735707 and NCT04479163.
Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children
Authors: Forsström Ville , Toivonen Laura , Homil Kiara , Waris Matti , Pedersen Casper-Emil T , Bønnelykke Klaus , Jartti Tuomas , Peltola Ville
Published: March 2023

Background

Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in early childhood is unclear.

Methods

We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 preselected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies.

Results

The asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01–1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01–1.20, P = .03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses.

Conclusions

Asthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors.

Clinical Trials Registration. NCT00494624 and NCT00731575.
Thein vitroactivity of delafloxacin and comparator agents against bacterial pathogens isolated from patients with cancer
Authors: Gerges Bahgat , Rolston Kenneth , Shelburne Samuel A , Rosenblatt Joel , Prince Randall , Raad Issam
Published: March 2023

Background

Fluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the in vitro activity of delafloxacin and selected comparators against 560 bacterial pathogens isolated exclusively from patients with cancer.

Methods

Antimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer.

Results

Delafloxacin was more active than ciprofloxacin and levofloxacin against Staphylococcus aureus and CoNS. Overall, 63% of staphylococcal isolates were susceptible to delafloxacin, 37% to ciprofloxacin and 39% to levofloxacin. Activity of delafloxacin against most Enterobacterales was similar to that of ciprofloxacin and levofloxacin. Escherichia coli and MDR Pseudomonas aeruginosa isolates had low susceptibility rates to the three tested fluoroquinolones. In time-kill studies delafloxacin and levofloxacin decreased the bacterial load to 3.0 log10 in 8 and 13 h, respectively, using 8 × MIC.

Conclusions

Delafloxacin is more active than ciprofloxacin and levofloxacin against S. aureus but has substantial gaps in coverage against GNB. Resistance to all three fluoroquinolones could be high among leading GNB such as E. coli and P. aeruginosa, particularly in cancer centres where these agents are widely used as prophylactic agents.
Integrating economic considerations into cutpoint selection may help align clinical decision support toward value-based healthcare
Authors: Parsons Rex , Blythe Robin , Cramb Susanna M , McPhail Steven M
Published: March 2023

Objective

Clinical prediction models providing binary categorizations for clinical decision support require the selection of a probability threshold, or “cutpoint,” to classify individuals. Existing cutpoint selection approaches typically optimize test-specific metrics, including sensitivity and specificity, but overlook the consequences of correct or incorrect classification. We introduce a new cutpoint selection approach considering downstream consequences using net monetary benefit (NMB) and through simulations compared it with alternative approaches in 2 use-cases: (i) preventing intensive care unit readmission and (ii) preventing inpatient falls.

Materials and methods

Parameter estimates for costs and effectiveness from prior studies were included in Monte Carlo simulations. For each use-case, we simulated the expected NMB resulting from the model-guided decision using a range of cutpoint selection approaches, including our new value-optimizing approach. Sensitivity analyses applied alternative event rates, model discrimination, and calibration performance.

Results

The proposed approach that considered expected downstream consequences was frequently NMB-maximizing compared with other methods. Sensitivity analysis demonstrated that it was or closely tracked the optimal strategy under a range of scenarios. Under scenarios of relatively low event rates and discrimination that may be considered realistic for intensive care (prevalence = 0.025, area under the receiver operating characteristic curve [AUC] = 0.70) and falls (prevalence = 0.036, AUC = 0.70), our proposed cutpoint method was either the best or similar to the best of the compared methods regarding NMB, and was robust to model miscalibration.

Discussion

Our results highlight the potential value of conditioning cutpoints on the implementation setting, particularly for rare and costly events, which are often the target of prediction model development research.

Conclusions

This study proposes a cutpoint selection method that may optimize clinical decision support systems toward value-based care.
Jie Geng Tang reverses cisplatin resistance through the Nrf2 pathway in lung cancer
Authors: Zhao Jing , Hou Manting , Ding Kaixin , Li Shixiong , Li Hui , Zhang Xili , Bai Zhaofang , Liu Wenlong
Published: March 2023

Objectives

Jie Geng Tang (JGT) is an ancient traditional Chinese herbal decoction that exhibits various pharmacological activities, however, is poorly understood in the sensitivity of lung cancer to chemotherapy. Here, we explored the effect of JGT on sensitizing cisplatin (DDP)-resistant A549 cells (A549/DDP).

Methods

Cell viability was assessed using cell counting kit-8 assay. Flow cytometry was applied to detected cell apoptosis, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. Western blotting and qRT-PCR were performed to determine protein and mRNA levels.

Key findings

The results demonstrated that DDP co-treatment with JGT significantly increased the cytotoxicity of A549/DDP cells and exhibited efficacy in suppressing the migration and proliferation. The rate of apoptosis was increased by co-treatment with DDP and JGT, along with a higher rate of Bax/Bcl-2, and increased loss of MMP. Furthermore, the combination promoted ROS accumulation and increased γ-H2AX levels. Moreover, Nrf2 levels were suppressed in a dose- and time-dependent manner, Nrf2 stability was reduced following treatment with JGT. Notably, the combination induced inhibition of the Nrf2/ARE pathway at the mRNA and protein levels.

Conclusions

Collectively, these results indicate that co-treatment with JGT and DDP can be considered a combinational approach to treating DDP resistance.
The Best Developed Man in Great Britain and Ireland? Eugen Sandow and the Commercialization of Eugenics in Twentieth-Century Britain
Authors: Heffernan Conor
Published: March 2023

In 1901 Eugen Sandow, a strong man performer turned health authority, hosted a competition in the Royal Albert Hall to determine the ‘best developed man in Great Britain and Ireland’. At the contest, members of the public, the military, and the scientific community watched as Sandow and his judges compared men’s physiques. Typically depicted by historians as a pivotal step in the development of bodybuilding as a sport, this article repositions Sandow’s contest as a public manifestation of British eugenics and concerns about physical deterioration. Welcoming a thousand competitors in its qualifying rounds, Sandow’s contest was advertised with reference to perfecting the British male body and stemming the tide of British degeneration. When the outbreak of the Second South African War in 1899 delayed the contest’s finale, Sandow’s marketers redoubled efforts to depict the contest as an antidote to the physical deterioration of British troops said to have become evident in the conflict. Here it is argued that Sandow simultaneously magnified, and profited, from a broader British eugenic concern about the male body. His competition served as a strong reminder for how widespread such concerns were in late Victorian and early Edwardian Britain and, more importantly, how they could be commercialized.
A rare occurrence of Anaplasma-associated peritonitis
Authors: Bush Valerie , Chaudhary Jitendra , Manu Devarajan , Hyman Charles
Published: March 2023

Anaplasmosis or human granulocytic anaplasmosis is a tick-borne illness caused by the bacteria, Anaplasma phagocytophilum, resulting from an infected tick bite. Examination of a blood smear within the first week of exposure may show microcolonies of anaplasmae (morulae) in the cytoplasm of neutrophils that are highly suggestive of anaplasmosis but not definitive. We present the first case describing Anaplasma-related peritonitis and morulae in peritoneal fluid granulocytes in a peritoneal dialysis patient who developed anaplasmosis.
Effectiveness of diphenyl diselenide against experimental sporotrichosis caused by Sporothrix brasiliensis
Authors: Munhoz Lívia Silveira , Poester Vanice Rodrigues , Benelli Jéssica Louise , Melo Aryse Martins , Trápaga Mariana Rodrigues , Nogueira Cristina Wayne , Zeni Gilson , Flores Mariana Martins , Stevens David A , Xavier Melissa Orzechowski
Published: March 2023

Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (P < .001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.
A biotic habitable zone: impacts of adaptation in biotic temperature regulation
Authors: Nicholson A E , Mayne N J
Published: March 2023

The search for biosignatures necessitates developing our understanding of life under different conditions. If life can influence the climate evolution of its planet then understanding the behaviour of life-climate feedbacks under extreme conditions is key to determine the ‘edges’ of the habitable zone. Additionally understanding the behaviour of a temperature limited biosphere will help towards formulating biosignature predictions for alien life living under conditions very different to those on Earth. Towards this aim, we extend the ‘ExoGaia Model’ – an abstract model of microbial life living on a highly simplified zero-dimensional planet. Via their metabolisms, microbes influence the atmospheric composition and therefore the temperature of the planet and emergent feedback loops allow microbes to regulate their climate and maintain long-term habitability. Here, we adapt the ExoGaia model to include temperature adaptation of the microbes by allowing different species to have different temperature ‘preferences’. We find that rather than adapting towards the planet’s abiotic conditions the biosphere tends to more strongly influence the climate of its planet, suggesting that the surface temperature of an inhabited planet might be significantly different from that predicted using abiotic models. We find that the success rate for microbial establishment on planets is improved when adaptation is allowed. However, planetary abiotic context is important for determining whether overall survival prospects for life will be improved or degraded. These results indicate the necessity to develop an understanding of life living under different limiting regimes to form predictions for the boundaries of the habitable zone.