bluuebunny/crossref_metadata_2025 huggingface dataset:
P662 A retrospective claims analysis on the prevalence and incidence of ulcerative colitis in Germany and the frequency of advanced therapy use
Authors: Mueller S , Khalid M , Patel H , Wilke T , Dittmar A
Published: May 2021

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that requires continuous medical treatment. Current epidemiological data about UC in Germany are lacking, and in particular, it is unknown how many patients are treated with advanced therapies.

This study aimed to investigate the prevalence and incidence of UC in Germany and describe the frequency of advanced therapy use in this population.

Methods

We used claims data from a regional German sickness fund (AOK PLUS). Continuously insured persons from 01/01/2015 until 31/12/2019 or death with at least 2 outpatient diagnoses documented by a specialist in 2 quarters within 12 months or one inpatient diagnosis (ICD-10: K51.-) were defined to be UC prevalent. Patients were defined to be incident in 2019 if the respective selection criteria could be observed in 2019, but no UC diagnosis was documented in the previous 4 years.

Age- and gender-standardized point prevalence was calculated on 01/01/2019, cumulative incidence was evaluated for the year 2019. Standardization was based on the age/gender distribution within the entire population of the German statutory insurance (KM-6 statistic), which covers about 90% of the whole German population.

Main characteristics and comorbidity status were assessed at the index date based on diagnoses documented in the 12-month pre-index period (index: 01/01/2019 or date of incident diagnosis in 2019).

The proportion of prevalent patients receiving advanced therapies (infliximab, adalimumab, golimumab, vedolizumab, tofacitinib) was evaluated in 2019, considering both out- and inpatient treatments.

Results

The standardized incidence in 2019 was 0.36 cases/1,000 persons. Incident patients were, on average, 59.7 years old (SD: 21.6; 95% CI: 58.2–61.1), and 56.1% were females. The mean Charlson Comorbidity Index (CCI) was 2.7 (SD: 3.1; 95% CI: 2.5–2.9).

The standardized prevalence at 01/01/2019 was 5.29 cases/1,000 persons. In 2019, 12,736 prevalent patients were observed (12,510.8 person-years), with 56.2% of the patients being female. The mean age was 60.6 years (SD: 18.8; 95% CI: 60.2–60.9), and the mean CCI was 2.3 (SD: 2.8; 95% CI: 2.2–2.3). 827 patients (6.5%) were treated with advanced therapy in 2019. These patients were considerably younger (44.9 (95% CI: 43.9–46.0) versus 61.7 years (95% CI: 61.3–62.0)) and less comorbid (CCI: 1.2 (95% CI: 1.0–1.3) vs. 2.4 (95% CI: 2.3–2.4)) than patients who have not been treated with an advanced therapy.

Conclusion

Our analysis showed a considerable UC incidence and a high disease burden in Germany, with a prevalence surpassing 0.5%. Advanced therapies were prescribed only in a minority of UC patients, who were generally younger and less comorbid.
P663 Long-term follow up in IBD: 10-year observational study of a UK IBD cohort
Authors: Radhakrishnan S T , Vasireddy A , Gallagher K I , Hicks L C , Powles S T , Chong L , Peake S T , Orchard T R , Williams H R T
Published: May 2021

Background

Crohn’s Disease (CD) and ulcerative colitis (UC) are the two main sub-types of Inflammatory Bowel disease (IBD), which affect 300–500 per 100,000 people within Europe, with an increasing incidence. Long-term outcomes have been reported cohorts of Korean and Scandinavian populations, but long-term UK data are limited.

Methods

Data were prospectively collected from an IBD cohort over a 10-year period. 90 patients were included (47 CD, 36 UC, 7 IBD-unclassified). Phenotypic data (Montreal classification), medication and management decisions were documented. Statistical significance was determined by the Z-score for 2 population proportions.

Results

Over 10 years, the number of operations for CD significantly increased from 8 to 19 patients (p=0.03) but not significantly in UC from 1 to 4 (p=0.09). Perianal involvement in CD also increased from 15.5% to 27.7% at 10 years, but this change was non-significant (p=0.14). Within the UC cohort, a trend for aminosalicylate use was seen, increasing from 53% to 64% (p=0.34), whilst thiopurine use decreased from 44% to 28% (p=0.12). 6/36 patients with UC and 10/47 patients with CD failed thiopurine use due to intolerance or severe side-effects. Biologic use in both UC and CD significantly increased from 10 to 22 patients (p=0.013) over 10 years.

Conclusion

This is the first long-term observational study in IBD patients within the UK. The data show that even with an increase in biologic availability and prescribing, the overall lifetime risk of surgical management in CD does increase with time, mirroring recent publications. Studies with an increased number of IBD patients under long-term follow up are ongoing.
P664 Adherence to mesalazine and identification of patients with ulcerative colitis in healthcare administrative databases of Tuscany (Italy)
Authors: Bertani L , Bartolini C , Ferraro S , Convertino I , Giometto S , Tillati S , Valdiserra G , Cappello E , Blandizzi C , Lucenteforte E , Gini R , Tuccori M , Costa F
Published: May 2021

Background

Drug supply can be used to identify patients with a specific disease in healthcare administrative databases (HAD), particularly when they have a univocal indication. For drugs with multiple indications, other elements must be considered, such as dosing or scheduled regimen. This is the case of mesalazine (MZ), a drug indicated for ulcerative colitis (UC), but also for Crohn’s disease and other not classifiable inflammatory bowel diseases. The aim of the present study was to explore adherence trajectories to MZ, in the attempt of identifying variables useful to detect patients with UC in HAD

Methods

In this retrospective cohort study, data was retrieved from administrative healthcare databases in Tuscany. Patients who had at least a first MZ dispensation between 6/1/2011 and 6/30/2016 (index date, ID) were included. We performed four sub-group analyses: 1) Patients with at least 1 MZ dispensation in the follow-up (FUP); 2) Patients with at least 2 MZ dispensations in the first 3 months of FUP; 3) Patients with MZ dosage >1.5 grams between the 1st and the 2nd dispensation; 4) Patients with MZ dosage >2.5 grams between the 1st and the 2nd dispensation. Each sub-group was stratified by age: ≤65 and >65, separately. We estimated adherence to MZ monthly, through the Medication Possession Ratio and computed adherence trajectories with a 3 step-procedure: 1) computation of 24 statistical measures; 2) factor analysis; 3) cluster analysis. We performed two sensitivity analyses: 1) Patients >65 years old with UC ICD-9 code, 2) Patients ≤65 years old with the UC exemption code.

Results

The sub-groups 1, 2, 3 and 4 included 47.750, 34.037, 29.730 and 26.165 MZ users, respectively. In all the sub-groups and stratification by age, 3 clusters of adherence were identified: high, medium low and low. The high adherence trajectory showed a mean adherence over 40% in the FUP, while patients in the low and medium low trajectories discontinued MZ within 5 and 15 months, respectively. The first and second sensitivity analysis included 409 and 1514 patients, respectively. Two clusters were identified in both analyses: high, around 80%, and moderate, up to 30% at the end of FUP. No MZ discontinuation was observed in the sensitivity analyses on ascertained UC patients.

Conclusion

In the main analyses, two out of three trajectories were characterized by MZ discontinuation, while in the trajectories calculated for the patients with UC codes, no MZ use interruption was detected. This finding could help the identification of true UC patients in the overall population of MZ users.
Seismic crustal structure beneath Jeju Volcanic Island, South Korea from teleseismicP-receiver functions
Authors: Kang Hyunsun , Kim YoungHee , Rhie Junkee , Kang Tae-Seob , Brenna Marco
Published: May 2021

Jeju Island is an intraplate volcanic island with enigmatic origins, located on the continental shelf south of the Korean Peninsula. A dense temporary seismic array, operated on Jeju Island from 2013 to 2015, revealed several important constraints on the magma plumbing system of Jeju Island. In this study, we determined the deep crustal seismic structure beneath Jeju Island from the teleseismic P-to-S converted phases (receiver functions) recorded from 20 temporary and three permanent stations. We removed the contribution of near-surface reverberations in the resulting receiver functions by applying a resonance removal filter. We estimated crustal P-to-S velocity ratio (VP/VS) and discontinuity depth to provide teleseismic constraints on the composition and structure. We observed two major seismic discontinuities, which are the upper boundaries of a mid-to-lower crustal low-velocity zone (LVZ) and the Moho transition zone. The depth to the upper boundary of the LVZ is deep in the west and southeast (24–30 km) and shallow in the northeast (8–11 km). The LVZ can be interpreted as an extensively distributed residual magma plumbing system, with magma batches stalled at various levels and at various degrees of crystallization, consistent with the chemical diversity of Jeju magmas. The seismic characteristics of the Moho transition zone vary greatly among regions. The top interface of the Moho transition zone is at a wide range of depth (26–40 km), and is shallow at 26–29 km depths beneath central Jeju, suggesting a complex Moho topography. The presence of mafic cumulates and partially molten mushes may contribute to the observed shallow seismic discontinuity at a depth of 26–29 km. The lack of obvious crustal thickening below the shield volcano, Mt Halla, may be associated with mantle upwelling or presence of mafic underplating and cumulates below Jeju. Spatial variations of crustal VP/VS represent highly heterogeneous crustal composition, resulting from magma differentiation during the evolution of the island.
Perspectives on Individual Animal Identification from Biology and Computer Vision
Authors: Vidal Maxime , Wolf Nathan , Rosenberg Beth , Harris Bradley P , Mathis Alexander
Published: May 2021

Synopsis

Identifying individual animals is crucial for many biological investigations. In response to some of the limitations of current identification methods, new automated computer vision approaches have emerged with strong performance. Here, we review current advances of computer vision identification techniques to provide both computer scientists and biologists with an overview of the available tools and discuss their applications. We conclude by offering recommendations for starting an animal identification project, illustrate current limitations, and propose how they might be addressed in the future.
Tails, Flails, and Sails: How Appendages Improve Terrestrial Maneuverability by Improving Stability
Authors: Shield Stacey , Jericevich Ricardo , Patel Amir , Jusufi Ardian
Published: May 2021

Trade-offs in maneuverability and stability are essential in ecologically relevant situations with respect to robustness of locomotion, with multiple strategies apparent in animal model systems depending on their habitat and ecology. Free appendages such as tails and ungrounded limbs may assist in navigating this trade-off by assisting with balance, thereby increasing the acceleration that can be achieved without destabilizing the body. This comparative analysis explores the inertial mechanisms and, in some cases, fluid dynamic mechanisms by which appendages contribute to the stabilization of gait and perturbation response behaviors in a wide variety of animals. Following a broad review of examples from nature and bio-inspired robotics that illustrate the importance of appendages to the control of body orientation, two specific cases are examined through preliminary experiments: the role of arm motion in bipedal gait termination is explored using trajectory optimization, and the role of the cheetah’s tail during a deceleration maneuver is analyzed based on motion capture data. In both these examples, forward rotation of the appendage in question is found to counteract the unwanted forward pitch caused by the braking forces. It is theorized that this stabilizing action may facilitate more rapid deceleration by allowing larger or longer-acting braking forces to be applied safely.
Home range variation in leopards living across the human density gradient
Authors: Snider Matthew H , Athreya Vidya R , Balme Guy A , Bidner Laura R , Farhadinia Mohammed S , Fattebert Julien , Gompper Matthew E , Gubbi Sanjay , Hunter Luke T B , Isbell Lynne A , Macdonald David W , Odden Morten , Owen Cailey R , Slotow Rob , Spalton James A , Stein Andrew B , Steyn Villiers , Vanak Abi T , Weise Florian J , Wilmers Christopher C , Kays Roland
Published: May 2021

Home range size is a fundamental measure of animal space use, providing insight into habitat quality, animal density, and social organization. Human impacts increasingly are affecting wildlife, especially among wide-ranging species that encounter anthropogenic disturbance. Leopards (Panthera pardus) provide a useful model for studying this relationship because leopards coexist with people at high and low human densities and are sensitive to human disturbance. To compare leopard home range size across a range of human densities and other environmental conditions, we combined animal tracking data from 74 leopards in multiple studies with new analytical techniques that accommodate different sampling regimes. We predicted that home ranges would be smaller in more productive habitats and areas of higher human population density due to possible linkage with leopard prey subsidies from domestic species. We also predicted that male leopards would have larger home ranges than those of females. Home ranges varied in size from 14.5 km2 in India to 885.6 km2 in Namibia, representing a 60-fold magnitude of variation. Home range stability was evident for 95.2% of nontranslocated individuals and 38.5% of translocated individuals. Leopard home range sizes were negatively correlated with landscape productivity, and males used larger areas than females. Leopards in open habitats had a predicted negative correlation in home range size with human population density, but leopards in closed habitats used larger home ranges in areas with more people.
Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin Biopsy
Authors: Corrà Marta Francisca , Sousa Mafalda , Reis Inês , Tanganelli Fabiana , Vila-Chã Nuno , Sousa Ana Paula , Magalhães Rui , Sampaio Paula , Taipa Ricardo , Maia Luís
Published: May 2021

Intraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1–3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.
Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy
Authors: Saito Satoshi , Abe Takanori , Iino Misaki , Aoshika Tomomi , Ryuno Yasuhiro , Ohta Tomohiro , Igari Mitsunobu , Hirai Ryuta , Kumazaki Yu , Yamaguchi Ou , Kaira Kyoichi , Kagamu Hiroshi , Noda Shin-ei , Kato Shingo
Published: May 2021

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.
Elevated CO2 modulates the effect of heat stress responses inTriticum aestivumby differential expression of anisoflavone reductase-like gene
Authors: Shokat Sajid , Novák Ondřej , Široká Jitka , Singh Sukhwinder , Gill Kulvinder Singh , Roitsch Thomas , Großkinsky Dominik K , Liu Fulai
Published: May 2021

Two wheat genotypes forming high and low biomass, exhibiting differential expression of an isoflavone reductase-like (IRL) gene, and resulting in contrasting grain yield under heat stress field conditions were analyzed in detail for their responses under controlled heat and elevated CO2 conditions. Significant differences in IRL expression between the two lines were hypothesized to be the basis of their differential performance under the tested conditions and their stress tolerance potential. By a holistic approach integrating advanced cell physiological phenotyping of the antioxidative and phytohormone system in spikes and leaves with measurements of ecophysiological and agronomic traits, the genetic differences of the genotypes in IRL expression were assessed. In response to heat and elevated CO2, the two genotypes showed opposite regulation of IRL expression, which was associated with cytokinin concentration, total flavonoid contents, activity of superoxide dismutase, antioxidant capacity and photosynthetic rate in leaves, and cytokinin concentration and ascorbate peroxidase activity in spikes. Our study showed that IRL expression is associated with wheat yield performance under heat stress at anthesis, mediated by diverse physiological mechanisms. Hence, based on our results, the IRL gene is a promising candidate for developing genetic markers for breeding heat-tolerant wheat.
The COS-legacy survey of C iv absorbers: properties and origins of the intervening systems
Authors: Manuwal Aditya , Narayanan Anand , Udhwani Purvi , Srianand Raghunathan , Savage Blair D , Charlton Jane C , Misawa Toru
Published: May 2021

We present here results from a survey of intervening C iv absorbers at z < 0.16 conducted using 223 sightlines from the Hubble Spectroscopic Legacy Archive. Most systems (83%) out of the total sample of 69 have simple kinematics with 1 or 2 C iv components. In the 22 C iv systems with well constrained H i column densities, the temperatures from the b-values imply predominantly photoionized plasma (T ≤ 105 K) and non-thermal dynamics. These systems also have solar or higher metallicities. We obtain a C iv line density of $\mathrm{ d}\mathcal {N}/\mathrm{ d}X = 5.1\pm 1.0$ for $\log [N(\rm {C}\, \rm {{iv}})~(\rm {cm}^{-2})]\ge 12.9$, and $\Omega _{\rm {C}\, \rm {\rm {iv}}}=(8.01\pm 1.62) \times 10^{-8}$ for $12.9 \le \log [N(\rm {C}\, \rm {{iv}})~(\rm {cm}^{-2})] \le 15.0$. The C iv bearing diffuse gas in the z < 0.16 Universe has a metallicity of (2.07  ±  0.43) ×  10−3 Z⊙, an order of magnitude more than the metal abundances in the IGM at high redshifts (z ≳ 5), and consistent with the slow build-up of metals in the diffuse circum/intergalactic space with cosmic time. For z < 0.015 (complete above L > 0.01L⋆), the Sloan Digital Sky Survey provides a tentative evidence of declining covering fraction for strong C iv (N > 1013.5 cm−2) with ρ (impact parameter) and ρ/Rvir. However, the increase at high separations suggests that strong systems are not necessarily coincident with such galaxies. We also find that strong C iv absorption at z < 0.051 is not coincident with galaxy overdense regions complete for L > 0.13L⋆.
AniProtDB: A Collection of Consistently Generated Metazoan Proteomes for Comparative Genomics Studies
Authors: Barreira Sofia N , Nguyen Anh-Dao , Fredriksen Mark T , Wolfsberg Tyra G , Moreland R Travis , Baxevanis Andreas D
Published: May 2021

To address the void in the availability of high-quality proteomic data traversing the animal tree, we have implemented a pipeline for generating de novo assemblies based on publicly available data from the NCBI Sequence Read Archive, yielding a comprehensive collection of proteomes from 100 species spanning 21 animal phyla. We have also created the Animal Proteome Database (AniProtDB), a resource providing open access to this collection of high-quality metazoan proteomes, along with information on predicted proteins and protein domains for each taxonomic classification and the ability to perform sequence similarity searches against all proteomes generated using this pipeline. This solution vastly increases the utility of these data by removing the barrier to access for research groups who do not have the expertise or resources to generate these data themselves and enables the use of data from nontraditional research organisms that have the potential to address key questions in biomedicine.
Structural basis of successive adenosine modifications by the conserved ribosomal methyltransferase KsgA
Authors: Stephan Niklas C , Ries Anne B , Boehringer Daniel , Ban Nenad
Published: May 2021

Biogenesis of ribosomal subunits involves enzymatic modifications of rRNA that fine-tune functionally important regions. The universally conserved prokaryotic dimethyltransferase KsgA sequentially modifies two universally conserved adenosine residues in helix 45 of the small ribosomal subunit rRNA, which is in proximity of the decoding site. Here we present the cryo-EM structure of Escherichia coli KsgA bound to an E. coli 30S at a resolution of 3.1 Å. The high-resolution structure reveals how KsgA recognizes immature rRNA and binds helix 45 in a conformation where one of the substrate nucleotides is flipped-out into the active site. We suggest that successive processing of two adjacent nucleotides involves base-flipping of the rRNA, which allows modification of the second substrate nucleotide without dissociation of the enzyme. Since KsgA is homologous to the essential eukaryotic methyltransferase Dim1 involved in 40S maturation, these results have also implications for understanding eukaryotic ribosome maturation.
Heterogeneous delivery across the blood-brain barrier limits the efficacy of an EGFR-targeting antibody drug conjugate in glioblastoma
Authors: Marin Bianca-Maria , Porath Kendra A , Jain Sonia , Kim Minjee , Conage-Pough Jason E , Oh Ju-Hee , Miller Caitlyn L , Talele Surabhi , Kitange Gaspar J , Tian Shulan , Burgenske Danielle M , Mladek Ann C , Gupta Shiv K , Decker Paul A , McMinn Madison H , Stopka Sylwia A , Regan Michael S , He Lihong , Carlson Brett L , Bakken Katrina , Burns Terence C , Parney Ian F , Giannini Caterina , Agar Nathalie Y R , Eckel-Passow Jeanette E , Cochran Jennifer R , Elmquist William F , Vaubel Rachael A , White Forest M , Sarkaria Jann N
Published: May 2021

Background

Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. Understanding the mechanisms of failure for this promising strategy is critically important.

Methods

PDX models were employed to study efficacy of systemic vs intracranial delivery of Depatux-M. Immunofluorescence and MALDI-MSI were performed to detect drug levels in the brain. EGFR levels and compensatory pathways were studied using quantitative flow cytometry, Western blots, RNAseq, FISH, and phosphoproteomics.

Results

Systemic delivery of Depatux-M was highly effective in nine of 10 EGFR-amplified heterotopic PDXs with survival extending beyond one year in eight PDXs. Acquired resistance in two PDXs (GBM12 and GBM46) was driven by suppression of EGFR expression or emergence of a novel short-variant of EGFR lacking the epitope for the Depatux-M antibody. In contrast to the profound benefit observed in heterotopic tumors, only two of seven intrinsically sensitive PDXs were responsive to Depatux-M as intracranial tumors. Poor efficacy in orthotopic PDXs was associated with limited and heterogeneous distribution of Depatux-M into tumor tissues, and artificial disruption of the BBB or bypass of the BBB by direct intracranial injection of Depatux-M into orthotopic tumors markedly enhanced the efficacy of drug treatment.

Conclusions

Despite profound intrinsic sensitivity to Depatux-M, limited drug delivery into brain tumor may have been a key contributor to lack of efficacy in recently failed clinical trials.
A photosynthesis operon in the chloroplast genome drives speciation in evening primroses
Authors: Zupok Arkadiusz , Kozul Danijela , Schöttler Mark Aurel , Niehörster Julia , Garbsch Frauke , Liere Karsten , Fischer Axel , Zoschke Reimo , Malinova Irina , Bock Ralph , Greiner Stephan
Published: May 2021

Genetic incompatibility between the cytoplasm and the nucleus is thought to be a major factor in species formation, but mechanistic understanding of this process is poor. In evening primroses (Oenothera spp.), a model plant for organelle genetics and population biology, hybrid offspring regularly display chloroplast–nuclear incompatibility. This usually manifests in bleached plants, more rarely in hybrid sterility or embryonic lethality. Hence, most of these incompatibilities affect photosynthetic capability, a trait that is under selection in changing environments. Here we show that light-dependent misregulation of the plastid psbB operon, which encodes core subunits of photosystem II and the cytochrome b6f complex, can lead to hybrid incompatibility, and this ultimately drives speciation. This misregulation causes an impaired light acclimation response in incompatible plants. Moreover, as a result of their different chloroplast genotypes, the parental lines differ in photosynthesis performance upon exposure to different light conditions. Significantly, the incompatible chloroplast genome is naturally found in xeric habitats with high light intensities, whereas the compatible one is limited to mesic habitats. Consequently, our data raise the possibility that the hybridization barrier evolved as a result of adaptation to specific climatic conditions.
Factors Negatively Influencing Postoperative Improvement After Laminoplasty in Degenerative Cervical Myelopathy
Authors: Inose Hiroyuki , Yoshii Toshitaka , Kimura Atsushi , Takeshita Katsushi , Inoue Hirokazu , Maekawa Asato , Endo Kenji , Furuya Takeo , Nakamura Akira , Mori Kanji , Kanbara Shunsuke , Imagama Shiro , Seki Shoji , Matsunaga Shunji , Okawa Atsushi
Published: May 2021

Study Design:

This was a retrospective study of prospectively collected data.

Objective:

In this study, we aimed to characterize a population of patients with degenerative cervical myelopathy (DCM) and a history of poor postoperative neurological recovery and to identify risk factors associated with poor neurological recovery after laminoplasty.

Summary of Background Data:

Kyphotic cervical alignment has been considered a relative contraindication to laminoplasty in recent years; hence, laminoplasty has been decreasingly performed for the treatment of DCM in patients with cervical kyphosis. However, the effect of global spinal alignment on postoperative outcomes has not been extensively investigated.

Materials and Methods:

We prospectively enrolled patients who were scheduled for laminoplasty for DCM. Outcome (at enrollment and 1 y after surgery) and risk factor analyses were performed by comparing the good recovery and poor recovery groups. The Spearman correlation coefficient was used to evaluate the relationships between the recovery rate and the preoperative radiographic factors.

Results:

In total, 101 patients completed the 1-year follow-up. Regarding clinical outcomes, the Japanese Orthopedic Association score for the assessment of cervical myelopathy, European Quality of Life-5 Dimensions, and Neck Disability Index scores improved postoperatively. The recovery rate was significantly correlated with the preoperative sagittal vertical axis (SVA). The patients in the poor recovery group were older than those in the good recovery group. Univariate analyses showed that the SVA and T1 pelvic angle were significantly higher in the poor recovery group. Lastly, stepwise logistic regression analysis showed that a higher SVA was an independent predictor of poor recovery after laminoplasty.

Conclusions:

The SVA and T1 pelvic angle were significantly higher in the poor recovery group. A high preoperative SVA is an independent predictor for poor recovery after laminoplasty. Therefore, indications for laminoplasty in elderly DCM patients with a high preoperative SVA should be carefully considered.

Level of Evidence:

Level III.
Flow-through Anterolateral Thigh Flaps: Report of 3 Consecutive Cases and Review of its Utility
Authors: Saad Noah H. , Rosso Kelly , Wang Howard , Cromack Douglas , Karamanos Efstathios
Published: May 2021

In the field of plastic and reconstructive surgery, soft tissue reconstruction of Gustilo 3B with peripheral vascular disease or 3C fractures is a complex treatment algorithm. The concomitant issue of soft tissue coverage with vascular reconstruction is the main challenge when opting for free tissue transfer. The flow-through flap offers the surgeon the ability to treat a vascular injury or high-grade stenosis to maintain distal perfusion, while also providing soft tissue coverage. In this study, we present a case series of 3 patients who underwent flow-through anterolateral thigh free flap for lower extremity soft tissue coverage. Each patient had a history of trauma and either single vessel runoff or a dominant branch with diminutive secondary blood flow to the foot. All patients successfully underwent free flap reconstruction of lower extremity wounds while concomitantly reconstructing diseased arterial supply. Only 1 patient suffered partial flap loss postoperatively that was treated with debridement and split thickness skin grafting. Flow-through free tissue transfer is a valuable treatment option not only in Gustilo 3C fractures requiring soft tissue coverage, but also in patients with Gustilo 3B fractures with peripheral vascular disease.
Posttreatment Lyme Disease Syndrome—What It Might Be and What It Is Not
Authors: Schmid Hanna , Heininger Ulrich
Published: May 2021

Lyme disease is a multisystem disease caused by Borrelia burgdorferi infection and accounts for well-defined manifestations, appearing either at an early or late stage. Appropriate antibiotic therapy generally leads to a favorable outcome. Still, unspecific persisting symptoms such as fatigue, myalgia, arthralgia or cognitive dysfunction are reported by several patients months to years after adequate treatment. Their underlying pathophysiologic mechanism is unclear. However, there is no evidence for microbiological persistence in these cases and attempts to resolve the symptoms by repeated or prolonged antibiotic treatment have not been convincingly successful, but they may rather be harmful. To narrow down the controversially handled entity of posttreatment Lyme disease syndrome (PTLDS) and to avoid overdiagnosis and overtreatment, case definitions have been proposed, acknowledging PTLDS as a complex of nonspecific, subjective symptoms, which are neither caused by ongoing infection nor by any other identifiable disease. PTLDS is mainly a diagnosis of exclusion and requires careful evaluation of differential diagnosis followed by counseling about optimal management in light of missing specific therapeutic options.
Extracorporeal Membrane Oxygenation for Pediatric Burn Patients: Is Management Improving Over Time?
Authors: Suzuki Yota , Williams Taylor P. , Patino Joshua , Zhu Min , Colvill Kayla M. , Brooks Kaelyn , Radhakrishnan Ravi S.
Published: May 2021

Over the last few decades, extracorporeal membrane oxygenation (ECMO) has become a lifesaving modality for patients with severe respiratory failure following burn injury. With the advancement in critical care and ECMO management, this study aims to analyze the outcomes of ECMO in pediatric burn patients. The Extracorporeal Life Support Organization database was queried from 1999 to 2018 for patients 18 years old and under with a burn injury. The data were divided into two decades, the first (1999–2008) and the second (2009–2018), for analysis of background characteristics and clinical outcomes. Ninety-five patients met inclusion criteria. The overall use of ECMO increased in the second decade (60 cases) when compared to the first decade (35 cases), and use of venovenous ECMO increased in the second decade from 16 cases to 38 cases. Although more patients survived because of the increased application of venovenous ECMO, the survival rate was unchanged between decades (53.4% vs. 54.3%; P = 0.937). Patients with pre-ECMO cardiac arrest had a significant improvement in mortality during the second decade (54.5% vs. 0%; P = 0.043). Metabolic (P = 0.022) and renal (P = 0.043) complications were most common in nonsurvivors during the first decade whereas cardiovascular (P = 0.031) and neurologic (P = 0.003) complication were higher in the second decade (P = 0.031, 0.003). Use of ECMO after burn injury has become more common; however, overall mortality remains unchanged. The data suggests pre-ECMO cardiac arrest is no longer a contraindication to start ECMO.
Pathophysiology of cardiogenic shock
Authors: Bertini Pietro , Guarracino Fabio
Published: May 2021

Purpose of review

We describe the pathophysiology of cardiogenic shock (CS), from the main pathways to the inflammatory mechanisms and the proteomic features.

Recent findings

Although the classical pathophysiological pathways underlying CS, namely reduced organ perfusion due to inadequate cardiac output and peripheral vasoconstriction, have been well-established for a long time, the role of macro-and micro-hemodynamics in the magnitude of the disease and its prognosis has been investigated extensively only over the last few years. Moreover, to complete the complex picture of CS pathophysiology, the study of cytokine cascade, inflammation, and proteomic analysis has been addressed recently.

Understanding the pathophysiology of CS is important to treat it optimally.
Limits of the Glasgow Coma Scale When Assessing for Sepsis in Allogeneic Hematopoietic Cell Transplant Recipients
Authors: Lind Margaret L. , Rosas Mirta Maravilla , McFarland Lindsay , Taylor Lenise , Olson Sandra , Pergam Steven A.
Published: May 2021

Background

The well-documented association between acute mental status changes and sepsis development and progression makes acute mental status an attractive factor for sepsis screening tools. However, the usefulness of acute mental status within these criteria is limited to the frequency and accuracy of its capture. The Glasgow Coma Scale (GCS) score—the acute mental status indicator in many clinical sepsis criteria—is infrequently captured among allogeneic hematopoietic cell transplant recipients with suspected infections, and its ability to serve as an indicator of acute mental status among this high-risk population is unknown.

Objective

We evaluated the GCS score as an indicator of acute mental status during the 24 hours after suspected infection onset among allogeneic hematopoietic cell transplant recipients.

Methods

Using data from the first 100 days posttransplant for patients transplanted at a single center between September 2010 and July 2017, we evaluated the GCS score as an indicator of documented acute mental status during the 24 hours after suspected infection onset. From all inpatients with suspected infections, we randomly selected a cohort based on previously published estimates of GCS score frequency among hematopoietic cell transplant recipients with suspected infections and performed chart review to ascertain documentation of clinical acute mental status within the 24 hours after suspected infection onset.

Results

A total of 773 patients had ≥1 suspected infections and experienced 1,655 suspected infections during follow-up—625 of which had an accompanying GCS score. Among the randomly selected cohort of 100 persons with suspected infection, 28 were accompanied with documented acute mental status, including 18 without a recorded GCS. In relation to documented acute mental status, the GCS had moderate to high sensitivity and high specificity.

Discussion

These data indicate that, among allogeneic hematopoietic cell transplant recipients with suspected infections, the GCS scores are infrequently collected and have a moderate sensitivity. If sepsis screening tools inclusive of acute mental status changes are to be used, nursing teams need to increase measurement of GCS scores among high sepsis risk patients or identify a standard alternative indicator.
Case Report: Unilateral Cranial Nerve IV Palsy Secondary to Trochlear Schwannoma
Authors: Gebran Jason Jihad , Quan Amy Jill
Published: May 2021

SIGNIFICANCE

Cranial nerve IV palsy is the most common cranial nerve affected in both pediatric and adult patients with vertical and/or torsional diplopia. The condition has multiple known etiologies, including schwannoma, which is rarely reported in the literature. Schwannoma should be considered when the most common etiologies have been ruled out.

PURPOSE

This report documents a rare case of cranial nerve IV palsy secondary to a trochlear schwannoma. Treatment and management considerations will be discussed.

CASE REPORT

A 57-year-old man presented to the clinic for evaluation of his recent-onset vertical diplopia. He was diagnosed with left cranial nerve IV palsy. MRI of the brain and orbits revealed the presence of a schwannoma along the course of his left fourth cranial nerve. It did not compress any other cranial nerves or the brainstem. The patient was referred to the neuro-ophthalmology clinic for further evaluation. He was managed conservatively with prismatic spectacle correction to relieve his diplopia. Repeat MRI of the brain and orbits was recommended every 6 months.

CONCLUSIONS

Although rare, schwannoma of the fourth cranial nerve should be considered in cases of cranial nerve IV palsies without an obvious etiology. Neuroimaging of the brain and orbits is warranted in cases where more common etiologies have been ruled out or when other cranial nerves and/or the brainstem are involved.
Effect of Hygiene Procedures on Lens Case Contamination with Povidone-Iodine or Multipurpose Disinfecting Solutions
Authors: Nakagawa Masahiro , Nakagawa Ritsue , Willcox Mark D. P. , Vijay Ajay Kumar
Published: May 2021

SIGNIFICANCE

A multipurpose disinfecting solution (MPDS), which contains povidone-iodine (PI) as a disinfectant, has high disinfecting efficacy not only on planktonic bacterium but also on the case biofilms. The addition of case hygiene practice removed more bacteria from cases than MPDS alone.

PURPOSE

This study compared the ability of two MPDSs, one containing PI and another containing polyaminopropyl biguanide and polyquaternium, to reduce bacterial numbers in solution or adhered to the cases following case hygiene procedures.

METHODS

Bacterial strains (Delftia acidovorans, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Serratia marcescens, Staphylococcus aureus, and Staphylococcus epidermidis) were exposed to the MPDSs for the recommended disinfection times, and the viable number evaluated according to ISO 14729. Cases were inoculated with bacterial strains and incubated for 24 hours to allow for biofilm formation. Cases were disinfected with both disinfecting solutions for 4 hours and rinsed, followed by recapping or air-drying, or tissue-wiping and air-drying for 18 hours. The number of survivors was counted using standard culture techniques.

RESULTS

Both products exceeded the recommended 3-log reduction against planktonic bacteria. Regarding biofilm, after rinsing and recapping wet, the numbers of D. acidovorans (mean difference [95% confidence interval] log10 colony-forming units per case, −2.9 [0.8 to −4.6], P < .01), P. aeruginosa (−2.0 [0.5 to −3.1], P < .01), S. marcescens (−1.7 [0.8 to −3.5], P < .05), and S. epidermidis (−2.1 [0.6 to −3.5], P < .05) in PI cases were significantly lower than in the dual-disinfectant MPDS storage cases. After air-drying, the PI storage cases had significantly lower numbers of S. maltophilia (−2.6 [0.6 to −4.0], P < .01), D. acidovorans (−1.6 [0.7 to −3.3], P < .05), and S. aureus (−1.6 [0.7 to −3.1], P < .05). The addition of tissue-wiping reduced the bacterial numbers in the MPDS storage cases to levels in the PI storage cases.

CONCLUSIONS

Contact lens users should be recommended to tissue-wipe and air-dry their lens storage cases after disinfection with regular MPDS.
Practice Guideline: Use of Quantitative EEG for the Diagnosis of Mild Traumatic Brain Injury: Report of the Guideline Committee of the American Clinical Neurophysiology Society
Authors: Tenney Jeffrey R. , Gloss David , Arya Ravindra , Kaplan Peter W. , Lesser Ronald , Sexton Vicki , Nuwer Marc
Published: May 2021

Despite many decades of research, controversy regarding the utility of quantitative EEG (qEEG) for the accurate diagnosis of mild traumatic brain injury (mTBI) remains. This guideline is meant to assist clinicians by providing an expert review of the clinical usefulness of qEEG techniques for the diagnosis of mTBI. This guideline addresses the following primary aim: For patients with or without posttraumatic symptoms (abnormal cognition or behavior), does qEEG either at the time of injury or remote from the injury, as compared with current clinical diagnostic criteria, accurately identify those patients with mTBI (i.e., concussion)? Secondary aims included differentiating between mTBI and other diagnoses, detecting mTBI in the presence of central nervous system medications, and pertinence of statistical methods for measurements of qEEG components. It was found that for patients with or without symptoms of abnormal cognition or behavior, current evidence does not support the clinical use of qEEG either at the time of the injury or remote from the injury to diagnose mTBI (level U). In addition, the evidence does not support the use of qEEG to differentiate mTBI from other diagnoses or detect mTBI in the presence of central nervous system medications, and suitable statistical methods do not exist when using qEEG to identify patients with mTBI. Based upon the current literature review, qEEG remains an investigational tool for mTBI diagnosis (class III evidence).
Serum antibodies to surface proteins ofChlamydia trachomatisas candidate biomarkers of disease: Results from the Baltimore Chlamydia Adolescent/Young Adult Reproductive Management (CHARM) cohort
Authors: Marques Patricia X. , Wand Handan , Nandy Melissa , Tan Chun , Shou Huizhong , Terplan Mishka , Mark Katrina , Brotman Rebecca M. , Wilson David P. , Ravel Jacques , Hsia Ru-ching , M. Bavoil Patrik
Published: May 2021

Background

We previously observed that the nine-member family of autotransported polymorphic membrane proteins (Pmps) ofChlamydia trachomatisis variably expressed in cell culture. Additionally,C. trachomatis-infected patients display variable Pmp-specific serum antibody profiles indirectly suggesting expression of unique Pmp profiles is an adaptive response to host-specific stimuli during infection. Here, we propose that the host response to Pmps and other outer surface proteins may correlate with disease severity.

Methods

This study tests this hypothesis using an ELISA that measures serum IgG antibodies specific for the nineC. trachomatisPmp subtypes and four immunodominant antigens (MOMP, OmcB, GroEL, ClpP) in 265 participants of theChlamydiaAdolescent/Young Adult Reproductive Management (CHARM) cohort.

Results

MoreC. trachomatis-infected females displayed high Pmp-specific antibody levels (cut-off Indexes) than males (35.9-40.7% of femalesvs. 24.2-30.0% of males), with statistical significance for PmpC, F and H (P<0.05). Differences in Pmp-specific antibody profiles were not observed betweenC. trachomatis-infected females with a clinical diagnosis of pelvic inflammatory disease (PID) and those without. However, a statistically significant association between high levels of OmcB-specific antibody and a PID diagnosis (P<0.05) was observed.

Conclusions

Using antibody levels as an indirect measure of antigen expression, our results suggest that gender- and/or site-specific (cervix in femalesvs. urethra in males) stimuli controlpmpexpression in infected patients. They also support the possible existence of immune biomarkers of chlamydial infection associated with disease and underline the need for high resolution screening in human serum.
Deep learning-based risk stratification for HER2-negative breast cancer patients
Authors: Jaber Mustafa I. , Beziaeva Liudmila , Szeto Christopher W. , Benz Stephen C.
Published: May 2021

In this paper, we present our analysis of the tumor microenvironment in digital pathology images to stratify risk in HER2-negative breast cancer patients using clinicopathological, spatial image, and cell-based features in a Cox’s proportional hazard model. We start the analysis by processing a set of 304 training pathology images using our in-house pan-cancer trained tumor, stroma, and lymphocyte region identification convolutional neural networks. The next step is computation of spatial regions of interest, namely: lymphocytes within (and adjacent to) tumor, lymphocytes within (and adjacent to) stroma, and stroma within (and adjacent to) tumor areas. Various cell-level information in these regions are then summarized, augmented to clinicopathological data, and linked to patient’s survival to train a Cox’s proportional hazards model. The proposed model outperformed a baseline model based on clinicopathological features only in analysis of an untouched test set of 202 whole slide images with p 8.49E-08 (HR = 0.4273).