bluuebunny/crossref_metadata_2025 huggingface dataset:
The GermAn Laser Lead Extraction RegistrY: GALLERY
Authors: Pecha Simon , Burger Heiko , Chung Da Un , Möller Viviane , Madej Tomas , Maali Alaa , Osswald Brigitte , De Simone Raffaele , Monsefi Nadeja , Ziaukas Virgilijus , Erler Stefan , Elfarra Hamdi , Perthel Mathias , Wehbe Mahmoud S , Ghaffari Naser , Sandhaus Tim , Busk Henning , Schmitto Jan D , Bärsch Volker , Easo Jerry , Albert Marc , Treede Hendrik , Nägele Herbert , Zenker Dieter , Hegazy Yasser , Ahmadi Donja , Gessler Nele , Ehrlich Wolfgang , Romano Gabriele , Knaut Michael , Reichenspurner Hermann , Willems Stephan , Butter Christian , Hakmi Samer
Published: April 2022

Aims

The GermAn Laser Lead Extraction RegistrY: GALLERY is a retrospective, national multicentre registry, investigating the safety and efficacy of laser lead extraction procedures in Germany.

Methods and results

Twenty-four German centres that are performing laser lead extraction have participated in the registry. All patients, treated with a laser lead extraction procedure between January 2013 and March 2017, were consecutively enrolled. Safety and efficacy of laser lead extraction were investigated. A total number of 2524 consecutive patients with 6117 leads were included into the registry. 5499 leads with a median lead dwell time of 96 (62–141) months were treated. The mean number of treated leads per patient was 2.18 ± 1.02. The clinical procedural success rate was 97.86% and the complete lead removal was observed in 94.85%. Additional extraction tools were used in 6.65% of cases. The rate of procedural failure was 2.14% with lead age  ≥10 years being its only predictor. The overall complication rate was 4.32%, including 2.06% major and 2.26% minor complications. Procedure-related mortality was 0.55%. Female sex and the presence of abandoned leads were predictors for procedure-related complications. The all-cause in-hospital mortality was 3.56% with systemic infection being the strongest predictor, followed by age ≥75 years and chronic kidney disease.

Conclusion

In the GALLERY, a high success- and low procedure-related complication rates have been demonstrated. In multivariate analysis, female sex and the presence of abandoned leads were predictors for procedure-related complications, while the presence of systemic infection, age ≥75 years, and chronic kidney disease were independent predictors for all-cause mortality.
Effects of intensive blood pressure control on cardiovascular and cognitive outcomes in patients with atrial fibrillation: insights from the SPRINT trial
Authors: Jiang Chao , Lai Yiwei , Du Xin , Wang Yufeng , Li Sitong , He Liu , Hu Rong , Lv Qiang , Wu Jiahui , Feng Li , Ning Man , Ruan Yanfei , Li Xu , Jia Changqi , Dai Wenli , Guo Xueyuan , Jiang Chenxi , Tang Ribo , Sang Caihua , Long Deyong , Arima Hisatomi , Dong Jianzeng , Anderson Craig S , Ma Changsheng
Published: April 2022

Aims

Patients with atrial fibrillation (AF) have an increased risk of cardiovascular events and dementia, even if anticoagulated. Hypertension is highly prevalent in AF population; however, the optimal blood pressure (BP) target for AF patients remains unknown.

Methods and results

We conducted subgroup analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) to examine whether AF modified the treatment effects of intensive BP control on cardiovascular and cognitive outcomes using Cox proportional hazards regression and likelihood ratio tests. Among 9361 randomized participants, 778 (8.3%) had baseline AF, and 695 (89.3%) completed at least one follow-up cognitive assessment. Intensive BP control reduced the similar relative risk of cardiovascular events irrespective of the presence of AF, with all interaction P-values > 0.05. Patients with AF experienced a greater absolute risk reduction in the composite primary cardiovascular outcome (12.3 vs. 5.6 events per 1000 person-years) with intensive treatment, compared with those without AF. However, intensive BP control increased the risk of probable dementia in patients with AF [hazard ratio (HR), 2.22; 95% confidence interval (CI), 1.03–4.80], while reducing the dementia risk in patients without AF (HR, 0.75; 95% CI, 0.60–0.95; P = 0.009 for interaction). There were no significant interactions between the presence of AF and intensive BP treatment for mild cognitive impairment.

Conclusion

Patients with AF experienced greater absolute cardiovascular benefits with intensive BP treatment, but may need to be cautious of an increased risk of dementia. This post hoc analysis should be considered as hypothesis generating and merit further study.

Clinical Trial Registration

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.
When Harry Met Sally: Older Adult Spouses’ First Encounter Reminiscing and Well-Being
Authors: Mroz Emily L , Shah Maya , Lan Hanzhen , Duker Ajua , Sperduto Maria , Levy Becca R , Monin Joan K
Published: April 2022

Background and Objectives

Interest in reminiscence activities for older adults has grown in recent years, but the benefits of co-reminiscence are not well-known. Drawing from a narrative identity framework, this study examined older adult spouses’ co-reminiscence about their first encounters. We hypothesized that perceived closeness and support increase when spouses co-reminisce and that greater perceptions of closeness and support after reminiscing relate to lower depressive symptoms and greater marital satisfaction in daily life.

Research Design and Methods

One hundred and one couples completed questionnaires measuring marital satisfaction and depressive symptoms at home and then participated in a laboratory session in which they co-reminisced about their first encounters. Self-reported perceived support and relationship closeness were obtained before and after reminiscence. t Tests and the Actor Partner Interdependence Model were used to examine hypotheses.

Results

As hypothesized, closeness and perceived support increased from pre- to postreminiscence for husbands and wives. In addition, one’s own relationship closeness after reminiscence was positively associated with own marital satisfaction (actor effect). One’s perceived support after reminiscence was positively related to spouse’s marital satisfaction and negatively associated with their spouse’s depressive symptoms (partner effects).

Discussion and Implications

Findings suggest that co-reminiscence about early relationship development can boost feelings of closeness and support for older adults. Benefiting from co-reminiscence in this way also appears to indicate broader relationship and individual well-being. Brief co-reminiscence activities may nurture late-life relational well-being.
Benchmarking missing-values approaches for predictive models on health databases
Authors: Perez-Lebel Alexandre , Varoquaux Gaël , Le Morvan Marine , Josse Julie , Poline Jean-Baptiste
Published: April 2022

Background

As databases grow larger, it becomes harder to fully control their collection, and they frequently come with missing values. These large databases are well suited to train machine learning models, e.g., for forecasting or to extract biomarkers in biomedical settings. Such predictive approaches can use discriminative—rather than generative—modeling and thus open the door to new missing-values strategies. Yet existing empirical evaluations of strategies to handle missing values have focused on inferential statistics.

Results

Here we conduct a systematic benchmark of missing-values strategies in predictive models with a focus on large health databases: 4 electronic health record datasets, 1 population brain imaging database, 1 health survey, and 2 intensive care surveys. Using gradient-boosted trees, we compare native support for missing values with simple and state-of-the-art imputation prior to learning. We investigate prediction accuracy and computational time. For prediction after imputation, we find that adding an indicator to express which values have been imputed is important, suggesting that the data are missing not at random. Elaborate missing-values imputation can improve prediction compared to simple strategies but requires longer computational time on large data. Learning trees that model missing values—with missing incorporated attribute—leads to robust, fast, and well-performing predictive modeling.

Conclusions

Native support for missing values in supervised machine learning predicts better than state-of-the-art imputation with much less computational cost. When using imputation, it is important to add indicator columns expressing which values have been imputed.
Standardized genome-wide function prediction enables comparative functional genomics: a new application area for Gene Ontologies in plants
Authors: Fattel Leila , Psaroudakis Dennis , Yanarella Colleen F , Chiteri Kevin O , Dostalik Haley A , Joshi Parnal , Starr Dollye C , Vu Ha , Wimalanathan Kokulapalan , Lawrence-Dill Carolyn J
Published: April 2022

Background

Genome-wide gene function annotations are useful for hypothesis generation and for prioritizing candidate genes potentially responsible for phenotypes of interest. We functionally annotated the genes of 18 crop plant genomes across 14 species using the GOMAP pipeline.

Results

By comparison to existing GO annotation datasets, GOMAP-generated datasets cover more genes, contain more GO terms, and are similar in quality (based on precision and recall metrics using existing gold standards as the basis for comparison). From there, we sought to determine whether the datasets across multiple species could be used together to carry out comparative functional genomics analyses in plants. To test the idea and as a proof of concept, we created dendrograms of functional relatedness based on terms assigned for all 18 genomes. These dendrograms were compared to well-established species-level evolutionary phylogenies to determine whether trees derived were in agreement with known evolutionary relationships, which they largely are. Where discrepancies were observed, we determined branch support based on jackknifing then removed individual annotation sets by genome to identify the annotation sets causing unexpected relationships.

Conclusions

GOMAP-derived functional annotations used together across multiple species generally retain sufficient biological signal to recover known phylogenetic relationships based on genome-wide functional similarities, indicating that comparative functional genomics across species based on GO data holds promise for generating novel hypotheses about comparative gene function and traits.
Full-waveform inversion by informed-proposal Monte Carlo
Authors: Khoshkholgh Sarouyeh , Zunino Andrea , Mosegaard Klaus
Published: April 2022

Markov chain Monte Carlo (MCMC) sampling of solutions to large-scale inverse problems is, by many, regarded as being unfeasible due to the large number of model parameters. This statement, however, is only true if arbitrary, local proposal distributions are used. If we instead use a global proposal, informed by the physics of the problem, we may dramatically improve the performance of MCMC and even solve highly nonlinear inverse problems with vast model spaces. We illustrate this by a seismic full-waveform inverse problem in the acoustic approximation, involving close to 106 parameters. The improved performance is mainly seen as a dramatic shortening of the burn-in time (the time used to reach at least local equilibrium), but also the algorithm’s ability to explore high-probability regions (through more accepted perturbations) is potentially better. The sampling distribution of the algorithm asymptotically converges to the posterior probability distribution, but as with all other inverse methods used to solve highly nonlinear inverse problems we have no guarantee that we have seen all high-probability solutions in a finite number of iterations. On the other hand, with the proposed method it is possible to sample more high-probability solutions in a shorter time, without sacrificing asymptotic convergence. This may be a practical advantage for problems with many parameters and computer-intensive forward calculations.
The VANDELS survey: a measurement of the average Lyman-continuum escape fraction of star-forming galaxies at z = 3.5
Authors: Begley R , Cullen F , McLure R J , Dunlop J S , Hall A , Carnall A C , Hamadouche M L , McLeod D J , Amorín R , Calabrò A , Fontana A , Fynbo J P U , Guaita L , Hathi N P , Hibon P , Ji Z , Llerena M , Pentericci L , Saldana-Lopez A , Schaerer D , Talia M , Vanzella E , Zamorani G
Published: April 2022

We present a study designed to measure the average Lyman-continuum escape fraction (〈fesc〉) of star-forming galaxies at z ≃ 3.5. We assemble a sample of 148 galaxies from the VANDELS spectroscopic survey at 3.35 ≤ zspec ≤ 3.95, selected to minimize line-of-sight contamination of their photometry. For this sample, we use ultra-deep, ground-based, U-band imaging and Hubble Space Telescope V-band imaging to robustly measure the distribution of $\mathcal {R_{\rm obs}}\, =(L_{\rm LyC}/L_{\rm UV})_{\rm obs}$. We then model the $\mathcal {R_{\rm obs}}$ distribution as a function of 〈fesc〉, carefully accounting for attenuation by dust, the intergalactic medium and the circumgalactic medium. A maximum likelihood fit to the $\mathcal {R_{\rm obs}}$ distribution returns a best-fitting value of $\langle f_{\rm esc}\rangle =0.07^{+0.02}_{-0.02}$, a result confirmed using an alternative Bayesian inference technique (both techniques exclude 〈fesc〉 = 0.0 at >3σ). By splitting our sample in two, we find evidence that 〈fesc〉 is positively correlated with Ly α equivalent width (Wλ(Ly α)), with high and low Wλ(Lyα) subsamples returning values of $\langle f_{\rm esc}\rangle =0.12^{+0.06}_{-0.04}$ and $\langle f_{\rm esc} \rangle =0.02^{+0.02}_{-0.01}$, respectively. In contrast, we find evidence that 〈fesc〉 is anticorrelated with intrinsic UV luminosity and UV dust attenuation; with low UV luminosity and dust attenuation subsamples both returning best fits in the range 0.10 ≤ 〈fesc〉 ≤ 0.22. We do not find a clear correlation between fesc and galaxy stellar mass, suggesting stellar mass is not a primary indicator of fesc. Although larger samples are needed to further explore these trends, our results suggest that it is entirely plausible that the low dust, low-metallicity galaxies found at z ≥ 6 will display the 〈fesc〉 ≥ 0.1 required to drive reionization.
Discovery and analysis of three magnetic hot subdwarf stars: evidence for merger-induced magnetic fields
Authors: Pelisoli Ingrid , Dorsch M , Heber U , Gänsicke B , Geier S , Kupfer T , Németh P , Scaringi S , Schaffenroth V
Published: April 2022

Magnetic fields can play an important role in stellar evolution. Among white dwarfs, the most common stellar remnant, the fraction of magnetic systems is more than 20 per cent. The origin of magnetic fields in white dwarfs, which show strengths ranging from 40 kG to hundreds of MG, is still a topic of debate. In contrast, only one magnetic hot subdwarf star has been identified out of thousands of known systems. Hot subdwarfs are formed from binary interaction, a process often associated with the generation of magnetic fields, and will evolve to become white dwarfs, which makes the lack of detected magnetic hot subdwarfs a puzzling phenomenon. Here we report the discovery of three new magnetic hot subdwarfs with field strengths in the range 300–500 kG. Like the only previously known system, they are all helium-rich O-type stars (He-sdOs). We analysed multiple archival spectra of the three systems and derived their stellar properties. We find that they all lack radial velocity variability, suggesting formation via a merger channel. However, we derive higher than typical hydrogen abundances for their spectral type, which are in disagreement with current model predictions. Our findings suggest a lower limit to the magnetic fraction of hot subdwarfs of $0.147^{+0.143}_{-0.047}$ per cent, and provide evidence for merger-induced magnetic fields which could explain white dwarfs with field strengths of 50–150 MG, assuming magnetic flux conservation.
Lags of the kilohertz quasi-periodic oscillations in the transient source XTE J1701−462
Authors: Peirano Valentina , Méndez Mariano
Published: April 2022

We analysed 14 observations with kilohertz quasi-periodic oscillations (kHz QPOs) of the neutron star X-ray binary XTE J1701−462, the first source to show a clear transition between atoll and Z-like behaviour during a single outburst. We calculated the average cross-spectrum of both atoll and Z-phase observations of XTE J1701−462 between a reference-hard band (6.1–25.7 keV) and a subject-soft band (2.1–5.7 keV) to obtain, using a novel technique, the average time lags of the lower and upper kHz QPOs. During the atoll phase, we found that at the frequency of the lower kHz QPO the soft photons lag behind the hard ones by 18 ± 8 $\mu$s, whereas during the Z phase the lags are 33 ± 35 $\mu$s, consistent with zero. This difference in the lags of both phases suggests that in XTE J1701−462, as observed in other sources, the lags decrease with increasing luminosity. We found that for both the atoll and Z-phase observations the fractional rms amplitude increases with energy up to ∼10 keV and remains more or less constant at higher energies. Since these changes in the variability of XTE J1701−462 occur within the same outburst, properties like the mass of the neutron star or the inclination of the system cannot be responsible for the differences in the timing properties of the kHz QPOs in the atoll and Z phase. Here, we suggest that these differences are driven by a Comptonizing component or corona, possibly oscillating in a coupled mode with the innermost regions of the accretion disc.
Overestimated inclinations of Milgromian disc galaxies: the case of the ultradiffuse galaxy AGC 114905
Authors: Banik Indranil , Nagesh Srikanth T , Haghi Hosein , Kroupa Pavel , Zhao Hongsheng
Published: April 2022

We present two hydrodynamical star-forming simulations in the Milgromian dynamics (MOND) framework of a gas-rich disc galaxy with properties similar to AGC 114905, which has recently been argued to have a rotation curve (RC) that is inconsistent with the MOND prediction. Our first model considers the galaxy in isolation, while our second model includes an external field of $0.05 \, a_{_0}$, the estimated gravitational field from large-scale structure. We show that isophotes in the face-on view can differ from circular at the 50 per cent level. This could mislead observers into overestimating the inclination i between disc and sky planes. Because RCs require a correction factor of 1/sin i, the actual RC could be much higher than that reported by observers. This plausibly reconciles AGC 114905 with MOND expectations.
A study of flares in the ultra-cool regime from SPECULOOS-South
Authors: Murray C A , Queloz D , Gillon M , Demory B O , Triaud A H M J , de Wit J , Burdanov A , Chinchilla P , Delrez L , Dransfield G , Ducrot E , Garcia L J , Gómez Maqueo Chew Y , Günther M N , Jehin E , McCormac J , Niraula P , Pedersen P P , Pozuelos F J , Rackham B V , Schanche N , Sebastian D , Thompson S J , Timmermans M , Wells R
Published: April 2022

We present a study of photometric flares on 154 low-mass (≤0.2 M⊙) objects observed by the SPECULOOS-South Observatory from 2018 June 1 to 2020 March 23. In this sample, we identify 85 flaring objects, ranging in spectral type from M4 to L0. We detect 234 flares in this sample, with energies between 1029.2 and 1032.7 erg, using both automated and manual methods. With this work, we present the largest photometric sample of flares on late-M and ultra-cool dwarfs to date. By extending previous M dwarf flare studies into the ultra-cool regime, we find M5–M7 stars are more likely to flare than both earlier, and later, M dwarfs. By performing artificial flare injection-recovery tests, we demonstrate that we can detect a significant proportion of flares down to an amplitude of 1 per cent, and we are most sensitive to flares on the coolest stars. Our results reveal an absence of high-energy flares on the reddest dwarfs. To probe the relations between rotation and activity for fully convective stars, we extract rotation periods for fast rotators and lower-bound period estimates of slow rotators. These rotation periods span from 2.2 h to 65 d, and we find that the proportion of flaring stars increases for the most fastest rotators. Finally, we discuss the impact of our flare sample on planets orbiting ultra-cool stars. As stars become cooler, they flare less frequently; therefore, it is unlikely that planets around the most reddest dwarfs would enter the ‘abiogenesis’ zone or drive visible-light photosynthesis through flares alone.
Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan
Authors: Ito Shuichi , Hataya Hiroshi , Ashida Akira , Hamada Riku , Ishikawa Tomoaki , Ishikawa Yumiko , Shimono Akihiko , Konomoto Takao , Miyazawa Tomoki , Ogura Masao , Tanaka Kazuki , Kagami Shoji
Published: April 2022

Background

Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting.

Methods

Paediatric patients in the PMS cohort who were <18 years of age at the first administration of eculizumab and diagnosed with aHUS [excluding Shiga toxin–producing Escherichia coli HUS, thrombotic thrombocytopaenic purpura and secondary thrombotic microangiopathy (TMA)] were included in the effectiveness and safety analysis. Clinical endpoints of effectiveness [complete TMA response, TMA event-free status, platelet (PLT) count and lactate dehydrogenase (LDH) normalization, serum creatinine (sCr) decrease and estimated glomerular filtration rate (eGFR) improvement] were analysed in patients treated with at least one dose of eculizumab. Serious adverse events (SAEs) were also evaluated.

Results

A total of 40 paediatric patients (median age 5 years) were included. The median eculizumab treatment duration was 66 weeks. PLT count, LDH and eGFR significantly improved at 10 days post-treatment. Complete TMA response, haematologic normalization, sCr decrease, eGFR improvement and TMA event-free status were achieved by 73.3%, 73.3%, 70.0%, 78.3% and 77.5% of patients, respectively. Discontinuation criteria were met by 18 patients: 13 patients maintained treatment discontinuation at the end of observation and 5 patients, including 1 patient with aHUS relapse, continued the treatment but extended the treatment interval. During eculizumab treatment, 59 SAEs (0.66/person-year) were reported. Although four deaths were reported, none of them were related to eculizumab.

Conclusion

Eculizumab was well tolerated and effective for paediatric patients with aHUS in the real-world setting in Japan.
Long-term impact of cardiorenal syndromes on major outcomes based on their chronology: a comprehensive French nationwide cohort study
Authors: Halimi Jean-Michel , de Fréminville Jean-Baptiste , Gatault Philippe , Bisson Arnaud , Gueguen Juliette , Goin Nicolas , Sautenet Bénédicte , Maisons Valentin , Herbert Julien , Angoulvant Denis , Fauchier Laurent
Published: April 2022

Background

Cardiorenal syndromes (CRSs) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown.

Methods

The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5 123 193 patients who were admitted in a French hospital in 2012).

Results

Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence), while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%).

The incidence of major outcomes was 57.3%, 53.0%, 79.2% for death; 18.8%, 10.9%, 27.5% for cardiovascular death; 52.6%, 34.7%, 64.3% for HF; 6.2%, 5.5%, 5.6% for myocardial infarction (MI); 6.1%, 5.8%, 5.3% for ischaemic stroke; and 23.1%, 4.8%, 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively.

As compared with isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischaemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared with isolated CKD, the risk of ESKD was similar for cardiorenal CRS only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5 123 193 patients).

Conclusions

The additional impact of CRS versus isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated.
The effect of silver fibre gloves on Raynaud’s phenomenon in patients with systemic sclerosis: a double-blind randomized crossover trial
Authors: Liem Sophie I E , Hoekstra Eva M , Bonte-Mineur Femke , Magro Checa César , Schouffoer Anne , Allaart Cornelia F , Huizinga Tom W J , Bergstra Sytske Anne , de Vries-Bouwstra Jeska K
Published: April 2022

Objectives

Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of RP in SSc patients. We aim to evaluate the clinical efficiency of this intervention.

Methods

A multicentre, double-blind, randomized trial was performed, accounting for interindividual differences and external factors using a crossover design. Patients were randomized in two groups: group 1 wore 8% silver fibre gloves in period 1 and normal gloves in period 2 and group 2 vice versa. Each period lasted 6 weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models.

Results

A total of 85 SSc patients were included, with 76 completing the study. The mean RCS during 2 weeks before the study (i.e. without gloves) was 6.4 (s.d. 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (s.d. 2.3) with a similar course over time. There was no difference in mean RCS over time between the type of gloves [β = 0.067 (95% CI −0.006, 0.19)]. Of secondary outcomes, total SHAQ [β = 0.036 (95% CI 0.026, 0.046)] was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves vs one patient with silver fibre gloves [odds ratio 3.2 (95% CI 0.32, 31.1)].

Conclusions

Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8% silver fibre gloves is associated with less disease burden as measured in this study by the RCS compared with normal gloves.

Clinical trial registration number

Netherlands Trial register (https://www.trialregister.nl/) NL7904
Comparative Efficacy and Safety of Lacosamide and Oxcarbazepine for Seizure Control in Children with Newly Diagnosed Solitary Neurocysticercosis
Authors: Sharawat Indar Kumar , Panda Prateek Kumar , Kumar Vinod , Sherwani Poonam
Published: April 2022

Background

In newly diagnosed neurocysticercosis (NCC) with seizures, the choice of anti-seizure medication (ASM) seems to be arbitrary due to a lack of comparative studies. Although oxcarbazepine (OXC) is often considered efficacious for focal seizures in NCC, due to adverse effects, newer ASMs like levetiracetam (LCM) and lacosamide are also being explored.

Methods

This study was performed by case record review of children with newly diagnosed solitary viable parenchymal NCC aged 4–18years who received lacosamide and OXC at least for 12 weeks between August 2019 and April 2021, from a prospective registry of a tertiary care teaching hospital in north India. Seizure control, electroencephalographic abnormalities, resolution of inflammatory granulomas and adverse effects were compared between two arms at 12 and 24 weeks.

Results

Total 31 (8.3 ± 4.7 years, 19 boys) and 72 (8.6 ± 4.2 years, 43 boys) completed at least 12 weeks follow-up in LCM and OXC groups, out of which 2 and 51 completed at least 24 weeks follow-up in LCM and OXC groups, respectively. The occurrence of breakthrough seizure was comparable in both arms at 12 and 24 weeks (1/31 and 2/22 in lacosamide group vs. 2/72 and 4/51 in OXC group, p = 0.66 and 0.59, respectively). Patients receiving OXC had more frequent treatment-emergent adverse events (p = 0.0001) and four patients required discontinuation due to severe adverse events (SAEs), while none in the lacosamide group had SAEs.

Conclusions

Lacosamide appears to be efficacious and safe for achieving seizure freedom in patients with solitary viable parenchymal neurocysticercosis.
Vaccination in Pediatric Patients with Sickle-Cell Disease: Uptake Report and Mini-Review
Authors: Jarovsky Daniel , Bastos Phillipe Romanzini , de Matos Samantha Faria , Almeida Flávia Jacqueline , Sáfadi Marco Aurélio Palazzi , Hegg Izabella Campos Oliveira , Luporini Silvia Maria , Berezin Eitan Naaman
Published: April 2022

Background

Brazil has one of the highest numbers of births with sickle-cell disease (SCD) in the Americas. Despite the risk of severe illnesses and death due to both vaccine-preventable infections, vaccination uptake in pediatric patients with SCD is unknown.

Material and methods

Children under 18 years with SCD presenting to routine medical consultations had their vaccination status evaluated according to the national recommendations. Data obtained were classified as ‘Adequate’, ‘Delayed’ or ‘Missing’ vaccination and compared among age groups.

Results

From 117 children screened, 100 had their vaccination card available. Vaccination coverage of routine vaccines was above 95% for all primary series and both age groups, with varied rates of delays and low missing doses. Among SCD extended vaccination, the most frequently delayed and missed vaccines were those specifically recommended to individuals with SCD as per national guidelines—and particularly those against encapsulated bacteria. Significant and varied rates of missing doses occurred in primary series and booster doses for PPSV23, Hib, menC, hepatitis A and varicella. The average influenza vaccination rate was 69.5%, with higher rates among younger children.

Conclusions

Children with SCD have alarming under-vaccination rates. Basic prevention strategies in Brazil should be reassessed in this specific population.
Cardiac Rehabilitation in Atrial Fibrillation Patients With Left Atrial Appendage Occlusion
Authors: Wu Yucheng , Lin Jie , Gong Benbingdi , Wang Lichun , Ruan Zhongbao , Xu Kai
Published: April 2022

Purpose:

Left atrial appendage (LAA) occlusion for atrial fibrillation (AF) is an invasive therapy that reduces stroke incidence and death. The impact of cardiac rehabilitation (CR) on patients with AF with LAA occlusion remains unknown. We aimed to evaluate the effects and safety of CR in patients with AF with LAA occlusion.

Methods:

This 6-mo single-center randomized controlled trial compared an exercise-based CR program with a control group. Patients with AF who underwent LAA occlusion from December 2018 to December 2020 were randomized into two groups: exercise-based CR and usual care (control). All patients underwent echocardiography, cardiac computed tomography, scale survey, physical function, and exercise capacity at baseline and at 3 and 6 mo follow-up.

Results:

There were 33 and 30 patients in the control and CR groups, respectively, in the final analysis. After the study period, the 6-min walk test distance, handgrip and leg strength, and left ventricular ejection fraction increased significantly in the CR group compared with baseline. Significant between-group differences were found in the mental and physical component summary scales, including all eight subscales, of the Short Form 36. The incidence of incomplete endothelialization in the CR group at 3 and 6 mo was significantly lower than that in the control group.

Conclusions:

Cardiac rehabilitation was shown to accelerate device endothelialization in patients with AF with LAA occlusion, while also improving the quality of life, exercise capacity, and physical function.
Primary Upper Extremity Lymphedema Caused by a CELSR1 Variant
Authors: Sudduth Christopher L. , Smits Patrick J. , Cheng Yu Sheng , Schmitz-Abe Klaus , Agrawal Pankaj , Greene Arin K.
Published: April 2022

Primary lymphedema of the upper extremity is rare and often is associated with syndromic or generalized lymphedema. The purpose of the study was to identify novel causes for primary lymphedema of the arm. A 17-year-old healthy male with right upper extremity swelling since infancy was confirmed to have lymphedema by lymphoscintigraphy. He subsequently developed right leg disease in adolescence and his mother had lower extremity lymphedema as well. Whole-exome sequencing of genomic DNA from the subject identified a frameshift deletion resulting in a premature stop codon in exon 3 of the CELSR1 gene hg19: chr22:46,835,160_46,835,166del (c.4326_4332del; p.T1443Gfs*14). The variant was confirmed in the patient and his mother by Sanger sequencing. A novel variant in CELSR1 causes nonsyndromic upper extremity lymphedema; other variants in this gene previously have been associated with lower extremity disease.
Intense 68Ga-FAPI Uptake in a Patient With Myositis Ossificans
Authors: Gong Weidong , Chen Si , He Lei , Liu Wei , Zhang Chunyin
Published: April 2022

A 72-year-old man presented with right hip pain, difficulty in walking, and a mass in his right hip for 3 months. CT suggested osteonecrosis of the right femoral head and a mass in the right hip with calcification. A malignancy was suspected, and the patient was subsequently enrolled in the clinical trial of 68Ga-FAPI. 68Ga-FAPI PET/CT showed a mass in his right hip with intense FAPI activity. It was also highly suggestive of malignancy. The pathological examination after right-hip surgery confirmed the diagnosis of myositis ossificans.
Textbook Outcome as a Quality Metric in Liver Transplantation
Authors: Schenk Austin D. , Han Jing L. , Logan April J. , Sneddon Jeffrey M. , Brock Guy N. , Pawlik Timothy M. , Washburn William K.
Published: April 2022

Background.

Quality in liver transplantation (LT) is currently measured using 1-y patient and graft survival. Because patient and graft survival rates now exceed 90%, more informative metrics are needed. Textbook outcomes (TOs) describe ideal patient outcomes after surgery. This study critically evaluates TO as a quality metric in LT.

Methods.

United Network for Organ Sharing data for 25 887 adult LT recipients were used to define TO as patient and graft survival >1 y, length of stay ≤10 d, 0 readmissions within 6 mo, absence of rejection, and bilirubin <3 mg/dL between months 2 and 12 post-LT. Univariate analysis identified donor and recipient characteristics associated with TO. Covariates were analyzed using purposeful selection to construct a multivariable model, and impactful variables were incorporated as linear predictors into a nomogram. Five-year conditional survival was tested, and center TO rates were corrected for case complexity to allow for center-level comparisons.

Results.

The national average TO rate is 37.4% (95% confidence interval, 36.8%-38.0%). The hazard ratio for death at 5 y for patients who do not experience TO is 1.22 (95% confidence interval, 1.11-1.34; P ≤ 0.0001). Our nomogram predicts TO with a C-statistic of 0.68. Center-level comparisons identify 31% of centers as high performing and 21% of centers as below average. High rates of TO correlate only weakly with center volume.

Conclusions.

The composite quality metric of TO after LT incorporates holistic outcome measures and is an important measure of quality in addition to 1-y patient and graft survival.
Phase II Trial Evaluating Esophageal Anastomotic Reinforcement with a Biologic, Degradable, Extracellular Matrix after Total Gastrectomy and Esophagectomy
Authors: Vos Elvira L , Nakauchi Masaya , Capanu Marinela , Park Bernard J , Coit Daniel G , Molena Daniela , Yoon Samuel S , Jones David R , Strong Vivian E
Published: April 2022

BACKGROUND:

A biologic, degradable extracellular matrix (ECM) has been shown to support esophageal tissue remodeling, which could reduce the risk of anastomotic leak following total gastrectomy and esophagectomy. We evaluated the safety and efficacy of reinforcing the anastomosis with ECM in reducing anastomotic leak as compared to a matched cohort.

STUDY DESIGN:

In this single-center, nonrandomized phase II trial, gastric or esophageal adenocarcinoma patients undergoing total gastrectomy or esophagectomy were recruited from November 2013 through December 2018. ECM was surgically wrapped circumferentially around the anastomosis. Anastomotic leak was assessed clinically and by contrast study and defined as clinically significant if requiring invasive treatment (grade 3 or higher). Anastomotic stenosis, other adverse events, symptoms, and dysphagia score were collected by standardized forms at regular follow-up visits at approximately postoperative days (POD) 21 and 90. Patients receiving ECM were compared to a cohort matched for surgery type and age.

RESULTS:

ECM placement was not feasible in 9 of 75 patients (12%), resulting in 66 patients receiving ECM. Total gastrectomy was performed in 50 patients (76%) and esophagectomy in 16 (24%). Clinically significant anastomotic leak was diagnosed in 6 of 66 patients (9.1%) (3/50 [6.0%] after gastrectomy, 3/16 [18.8%] after esophagectomy); this rate did not differ from that in the matched cohort (p = 0.57). Stenosis requiring invasive treatment occurred in 8 patients (12.5%), and 10 patients (15.6%) reported not being able to eat a normal diet at POD 90. No adverse events related to ECM were reported.

CONCLUSIONS:

Esophageal anastomotic reinforcement after total gastrectomy or esophagectomy with a biologic, degradable ECM was mostly feasible and safe, but was not associated with a statistically significant decrease in anastomotic leak.
Rectal Cancer in Patients with Hereditary Nonpolyposis Colorectal Cancer Compared with Sporadic Cases: Response to Neoadjuvant Chemoradiation and Local Recurrence
Authors: Madbouly Khaled M , Emile Sameh Hany , Issa Yasmine Amr
Published: April 2022

BACKGROUND:

This study aimed to assess the effect of neoadjuvant chemoradiation (nCXRT) on tumor regression and oncologic outcome of middle and low rectal cancer in patients of hereditary nonpolyposis colorectal cancer (HNPCC) compared to sporadic cases.

STUDY DESIGN:

This was a retrospective cohort study that compared the outcomes of patients with HNPCC presenting with middle or low rectal cancer indicated for nCXRT vs patients with sporadic rectal cancer. All patients received long-course nCXRT followed by total mesorectal excision. Primary outcome was pathologic tumor regression grade (TRG) assessed after resection. Secondary outcomes included disease-free survival and overall survival.

RESULTS:

Fifty-eight patients with HNPCC (24 female) were included in the study matched with 58 patients with sporadic rectal cancer (out of 166 using propensity score matching). Patients with HNPCC and sporadic rectal cancer were matched regarding tumor pathology TNM stage and lymphovascular invasion. In the HNPCC group, 36 patients (62%) had tumor regression (TRG3 = 6 (10.3%); TRG2 = 12 (20.6%); TRG1 = 18 (31%)) compared to 52 patients (92%) who had tumor regression in the control group (TRG4 = 9; TRG3 = 15; TRG2 = 18; TRG1 = 10) (p < 0.0007). After a median follow-up of 48 months, survival analysis revealed higher local recurrence and lower overall survival in patients with HNPCC compared to patients with sporadic rectal cancer.

CONCLUSIONS

Rectal cancer in patients with HNPCC showed poorer response to nCXRT and was followed by higher local recurrence and lower overall survival than patients with sporadic rectal cancer. Tumor regression was detected in <65% of patients with HNPCC compared to >90% of patients with sporadic rectal cancer, and none of patients with HNPCC had a complete response.
Combined multiple transcriptional repression mechanisms generate ultrasensitivity and oscillations
Authors: Jeong Eui Min , Song Yun Min , Kim Jae Kyoung
Published: April 2022

Transcriptional repression can occur via various mechanisms, such as blocking, sequestration and displacement. For instance, the repressors can hold the activators to prevent binding with DNA or can bind to the DNA-bound activators to block their transcriptional activity. Although the transcription can be completely suppressed with a single mechanism, multiple repression mechanisms are used together to inhibit transcriptional activators in many systems, such as circadian clocks and NF-κB oscillators. This raises the question of what advantages arise if seemingly redundant repression mechanisms are combined. Here, by deriving equations describing the multiple repression mechanisms, we find that their combination can synergistically generate a sharply ultrasensitive transcription response and thus strong oscillations. This rationalizes why the multiple repression mechanisms are used together in various biological oscillators. The critical role of such combined transcriptional repression for strong oscillations is further supported by our analysis of formerly identified mutations disrupting the transcriptional repression of the mammalian circadian clock. The hitherto unrecognized source of the ultrasensitivity, the combined transcriptional repressions, can lead to robust synthetic oscillators with a previously unachievable simple design.
Multi-synchronization and other patterns of multi-rhythmicity in oscillatory biological systems
Authors: Goldbeter Albert , Yan Jie
Published: April 2022

While experimental and theoretical studies have established the prevalence of rhythmic behaviour at all levels of biological organization, less common is the coexistence between multiple oscillatory regimes (multi-rhythmicity), which has been predicted by a variety of models for biological oscillators. The phenomenon of multi-rhythmicity involves, most commonly, the coexistence between two (birhythmicity) or three (trirhythmicity) distinct regimes of self-sustained oscillations. Birhythmicity has been observed experimentally in a few chemical reactions and in biological examples pertaining to cardiac cell physiology, neurobiology, human voice patterns and ecology. The present study consists of two parts. We first review the mechanisms underlying multi-rhythmicity in models for biochemical and cellular oscillations in which the phenomenon was investigated over the years. In the second part, we focus on the coupling of the cell cycle and the circadian clock and show how an additional source of multi-rhythmicity arises from the bidirectional coupling of these two cellular oscillators. Upon bidirectional coupling, the two oscillatory networks generally synchronize in a unique manner characterized by a single, common period. In some conditions, however, the two oscillators may synchronize in two or three different ways characterized by distinct waveforms and periods. We refer to this type of multi-rhythmicity as ‘multi-synchronization’.
A Method to improve the Reliability of Saliency Scores applied to Graph Neural Network Models in Patient Populations
Authors: Ochoa Juan G. Diaz , Mustafa Faizan E
Published: April 2022

Graph Neural Networks (GNN), a novel method to recognize features in heterogeneous information structures, have been recently used to model patients with similar diagnoses, extract relevant features and in this way predict for instance medical procedures and therapies. For applications in a medical field is relevant to leverage the interpretability of GNNs and evaluate which model inputs are involved in the computation of the model outputs, which is a useful information to analyze correlations between diagnoses and therapies from large datasets. We present in this work a method to sample the saliency scores of GNNs models computed with three different methods, gradient, integrated gradients, and DeepLIFT. The final sample of scores informs the customers if they are reliable if and only if all of them are convergent. This method will be relevant to inform customers which is the degree of confidence and interpretability of the computed predictions obtained with GNNs models.
Evaluation of Outdoor swimming courses as an intervention to refresh and revitalise NHS workers
Authors: Pett Pippa , Massey Heather , Denton Hannah , Burlingham Amy , Harper Mark
Published: April 2022

Background

Frontline healthcare staff working in the National Health Service (NHS) have been, and continue to be, under a significant level of work related stress as a result of the COVID-19 pandemic. Long hours and greater clinical need have impacted negatively on work-life balance. The results of our preliminary studies indicate that outdoor swimming may be an effective treatment for anxiety and depression. We therefore hypothesised that the activity could improve symptoms of work-related burnout and stress in NHS workers. The primary objective of this study was to gather feedback from NHS staff participating in supervised swimming sessions that took place in an outdoor pool in London and the sea in Cornwall on the value and effectiveness of this initiative as they perceived it.

Methods

Following ethical approval (University of Portsmouth Science and Health research ethics committee SHFEC 2021-066), participants who had signed up to outdoor swimming courses provided by NHS Improvement in Cornwall and London were asked to give their consent to participate in an online survey. They were asked to complete them at three time-points: the week prior to, upon completion and six weeks after completion of the outdoor swimming course. As well as being asked for qualitative feedback, participants completed the Short Warwick-Edinburgh Mental Wellbeing Scale and the Copenhagen Burnout Inventory.

Results

85 (63.9%) of the 133 Participants who signed up to outdoor swimming courses completed the first survey, 62 (49.6%) the second and 43 (35.5%) the third. 41 (33.8%) completed all three surveys. Overall, there was a 14.8% increase in wellbeing scores when comparing the scores before and after the courses which was statistically significant (p<0.0001, d= 1.02). Compared to scores before the course, the scores at its conclusion were reduced by 25%, 18% and 18% in personal, work-related and client-related burnout respectively. These burnout scores were significantly different for personal (P<0.0001) and work-related burnout (P=0.0018). Qualitative feedback was overwhelmingly positive with the effects being broadly divided into those relating to mood and physical health, the social aspects of the group activity, feelings of achievement and self-care and mindfulness.

Conclusion

This research suggests that the outdoor swimming activity, as a workplace intervention, can be an effective way of promoting staff wellbeing and reducing personal and work-related burnout. Further, formal trials of this intervention are justified.