bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost—tutorial and efficacy of complete directional hippocampal blocking
Authors: Popp Ilinca , Grosu Anca Ligia , Fennell Jamina Tara , Fischer Melissa , Baltas Dimos , Wiehle Rolf 
Published: March 2022

Abstract
Purpose
Hippocampus-avoidance whole brain radiotherapy with simultaneous integrated boost (HA-WBRT+SIB) is a complex treatment option for patients with multiple brain metastases, aiming to prevent neurocognitive decline and simultaneously increase tumor control. Achieving efficient hippocampal dose reduction in this context can be challenging. The aim of the current study is to present and analyze the efficacy of complete directional hippocampal blocking in reducing the hippocampal dose during HA-WBRT+SIB.

Methods
A total of 30 patients with multiple metastases having undergone HA-WBRT+SIB were identified. The prescribed dose was 30 Gy in 12 fractions to the whole brain, with 98% of the hippocampus receiving ≤ 9 Gy and 2% ≤ 17 Gy and with SIB to metastases/resection cavities of 36–51 Gy in 12 fractions. Alternative treatment plans were calculated using complete directional hippocampal blocking and compared to conventional plans regarding target coverage, homogeneity, conformity, dose to hippocampi and organs at risk.

Results
All alternative plans reached prescription doses. Hippocampal blocking enabled more successful sparing of the hippocampus, with a mean dose of 8.79 ± 0.99 Gy compared to 10.07 ± 0.96 Gy in 12 fractions with the conventional method (p < 0.0001). The mean dose to the whole brain (excluding metastases and hippocampal avoidance region) was 30.52 ± 0.80 Gy with conventional planning and 30.28 ± 0.11 Gy with hippocampal blocking (p = 0.11). Target coverage, conformity and homogeneity indices for whole brain and metastases, as well as doses to organs at risk were similar between planning methods (p > 0.003).

Conclusion
Complete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB.
Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results
Authors: Bukovszky B. , Fodor J. , Székely G. , Kocsis S. Zs. , Oberna F. , Major T. , Takácsi-Nagy Z. , Polgár C. , Jurányi Z. 
Published: March 2022

AbstractPurposeTo evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC.MethodsA survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996–2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c).ResultsMean follow-up time for all patients was 68 months (range: 5–288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3‑year cancer-specific survival was 23% with SPC.ConclusionAccording to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.
High return to sports and return to work rates after anatomic lateral ankle ligament reconstruction with tendon autograft for isolated chronic lateral ankle instability
Authors: Rupp Marco-Christopher , Degenhardt Hannes , Winkler Philipp W. , Hinz Maximilian , Ehmann Yannick J. , Imhoff Andreas B. , Pogorzelski Jonas , Themessl Alexander 
Published: March 2022

Abstract
Purpose
To evaluate clinical outcomes as well as return to sports (RTS) and return to work (RTW) rates following anatomic lateral ankle ligament reconstruction with a tendon autograft for chronic lateral ankle instability (CLAI) in a high-risk population, and to compare these outcome parameters between patients having received a gracilis tendon autograft (GT) and free split peroneus brevis tendon (PBT) autograft.

Methods
Twenty-eight consecutive patients, who were diagnosed with CLAI, presenting with ≥ 1 risk factor (ligamentous hyperlaxity, insufficient substance of native ligament and/or high-demand athlete), who underwent ankle ligament reconstruction with a tendon autograft between January 2011 and December 2018, were included in this retrospective study. At 63.7 ± 28.0 months (24–112), 23 patients with a mean age of 29.7 ± 10.9 years were available for follow-up. The Karlsson Score, the Foot and Ankle Outcome Score (FAOS), the Tegner Activity Scale and the visual analog scale (VAS) for pain were collected at a minimum follow-up of 24 months. RTS and RTW were evaluated by questionnaire. A subgroup analysis with regard to the graft used for ankle ligament reconstruction (GT versus PBT) was performed.

Results
Patients reported a Karlsson score of 82.1 ± 17.5 (37–100), a FAOS score of 87.8 ± 8.4 (73–99), a median Tegner activity scale of 5.0 (IQR 4–6) and a VAS for pain of 0.5 ± 0.9 (0–4) at rest and of 2.0 ± 2.1 (0–7) during activities at final follow-up. Postoperatively, 96% of patients had returned to sports after 8.3 ± 6.2 months. All patients (100%) had returned to work at 3.5 ± 5.7 (0–24) months, with 87% reporting an equal or improved working ability compared to that preoperatively. Postoperatively, exercise hours per week were significantly reduced compared to preoperatively in patients with a split PBT (n = 12; 13.0 ± 12.9 to 5.6 ± 6.4 h, p = 0.038) autograft as opposed to patients with a GT autograft (n = 11; 13.1 ± 8.7 to 12.4 ± 7.1 h, n.s.). No other group differences were observed.

Conclusion
Good patient-reported outcomes as well as excellent RTS and RTW rates can be achieved in high-risk patients undergoing ankle ligament reconstruction with a tendon autograft for CLAI. These results may be helpful in preoperatively managing patients’ expectations regarding sports- and work-related outcomes and provide tangible data on the expectable time frame of the individual return to sports and work trajectory.

Level of evidence
IV.
Poisson–Cournot games
Authors: De Sinopoli Francesco , Künstler Christopher , Meroni Claudia , Pimienta Carlos 
Published: March 2022

AbstractWe construct a Cournot model with uncertainty in the number of firms in the industry. We model such an uncertainty as a Poisson game and characterize the set of equilibria after deriving novel properties of the Poisson distribution. When marginal costs are zero, the number of equilibria increases with the expected number of firms (n) and for $$n\ge 3$$

n
≥
3

every equilibrium exhibits overproduction relative to the model with deterministic population size. For a fixed n, overproduction is robust to sufficiently small marginal costs. The set of equilibria can be Pareto ranked. If $$n\ge 3$$

n
≥
3

, even the expected consumer surplus induced by the lowest quantity equilibrium is larger than the consumer surplus in the model without population uncertainty.
A TMT-based shotgun proteomics uncovers overexpression of thrombospondin 1 as a contributor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome
Authors: Wang Weiqian , Chen Yan , Yin Yue , Wang Xunjiang , Ye Xuanling , Jiang Kaiyuan , Zhang Yi , Zhang Jiwei , Zhang Wei , Zhuge Yuzheng , Chen Li , Peng Chao , Xiong Aizhen , Yang Li , Wang Zhengtao 
Published: March 2022

AbstractHepatic sinusoidal obstruction disease (HSOS) is a rare but life-threatening vascular liver disease. However, its underlying mechanism and molecular changes in HSOS are largely unknown, thus greatly hindering the development of its effective treatment. Hepatic sinusoidal endothelial cells (HSECs) are the primary and essential target for HSOS. A tandem mass tag-based shotgun proteomics study was performed using primary cultured HSECs from mice with HSOS induced by senecionine, a representative toxic pyrrolizidine alkaloid (PA). Dynamic changes in proteome were found at the initial period of damage and the essential role of thrombospondin 1 (TSP1) was highlighted in PA-induced HSOS. TSP1 over-expression was further confirmed in human HSECs and liver samples from patients with PA-induced HSOS. LSKL peptide, a known TSP1 inhibitor, protected mice from senecionine-induced HSOS. In addition, TSP1 was found to be covalently modified by dehydropyrrolizidine alkaloids in human HSECs and mouse livers upon senecionine treatment, thus to form the pyrrole-protein adduct. These findings provide useful information on early changes in HSECs upon PA treatment and uncover TSP1 overexpression as a contributor in PA-induced HSOS.
Graphical abstract
Inter-annual variability in breeding census data across species and regions
Authors: Hays Graeme C. , Mazaris Antonios D. , Schofield Gail 
Published: March 2022

AbstractThere is an intense interest in long-term trends of species abundance that may reflect, for example, climate change or conservation actions. Less well studied are patterns in the magnitude of inter-annual variability in abundance across large spatial scales. We collated abundance time-series for 133 nesting sites across the globe of the seven sea turtle species. Inter-annual variability in nest numbers was lowest in loggerhead turtles (Caretta caretta), Kemp’s ridley (Lepidochelys kempii) and flatback turtle (Natator depressus) and highest in green turtles (Chelonia mydas), likely reflecting their lower trophic position compared to other species and hence tighter coupling of food availability to environmental conditions each year. The annual number of nests in green turtles could vary by 60-fold between successive years. We identified regional patterns in the magnitude of inter-annual variability in green turtle nest numbers, variability being highest for nesting beaches around Australia and lowest in the western Indian Ocean and equatorial Atlantic. These regional patterns are likely linked to corresponding patterns of environmental variability with, for example, areas subjected environmental extremes as part of the El Nino Southern Oscillation (ENSO) showing high inter-annual variability in nest numbers.
Bone marrow edema of the medioplantar talar head is associated with severe ligamentous injury in ankle sprain
Authors: Passon Tina , Germann Christoph , Fritz Benjamin , Pfirrmann Christian , Sutter Reto 
Published: March 2022

Abstract
Purpose
To investigate the predictive value of talar head edema (THE) in acute ankle sprain for the presence of concomitant ligament injuries.

Methods
This retrospective study was approved by the ethics committee and informed consent was obtained. One hundred patients (mean age: 37 years ± 14 [standard deviation], range 13–77 years) with MRI of the ankle after acute trauma were included. The cohort in this matched-pair study consisted of 50 patients with THE (group 1) and 50 patients without THE (group 2). Two readers independently evaluated presence and size of bone marrow edema of the talus head and injuries of the lateral, medial, talonavicular, and spring ligament complex. Statistics included intraclass correlation coefficient (ICC) and Kappa statistics as well as parametric and non-parametric tests.

Results
On average, patients with THE demonstrated significantly more ligament injuries in comparison to patients without THE (3.7 vs. 1.3, p ≤ 0.01). Also, in patients with THE, the number of injured ligaments was significantly higher at the lateral (p = 0.03), medial (p ≤ 0.01), and talonavicular (p ≤ 0.01) compartment in comparison to patients without THE. The most frequently injured ligaments in patients with THE were the anterior talofibular ligament (60%) and the anterior tibiotalar ligament (42%). There was no significant correlation between edema size and the number of injured ligaments or compartments (p = 0.5).

Conclusion
THE is associated with more extensive ligamentous ankle injury, in particular to the medial and lateral collateral ligament complex, and therefore indicative of severe ankle trauma.
Increased regional ventilation as early imaging marker for future disease progression of interstitial lung disease: a feasibility study
Authors: Scharm Sarah C. , Schaefer-Prokop Cornelia , Willmann Moritz , Vogel-Claussen Jens , Knudsen Lars , Jonigk Danny , Fuge Jan , Welte Tobias , Wacker Frank , Prasse Antje , Shin Hoen-oh 
Published: March 2022

Abstract
Objectives
Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and a highly variable course. Pathologically increased ventilation—accessible by functional CT—is discussed as a potential predecessor of lung fibrosis. The purpose of this feasibility study was to investigate whether increased regional ventilation at baseline CT and morphological changes in the follow-up CT suggestive for fibrosis indeed occur in spatial correspondence.

Methods
In this retrospective study, CT scans were performed at two time points between September 2016 and November 2020. Baseline ventilation was divided into four categories ranging from low, normal to moderately, and severely increased (C1–C4). Correlation between baseline ventilation and volume and density change at follow-up was investigated in corresponding voxels. The significance of the difference of density and volume change per ventilation category was assessed using paired t-tests with a significance level of p ≤ 0.05. The analysis was performed separately for normal (NAA) and high attenuation areas (HAA).

Results
The study group consisted of 41 patients (73 ± 10 years, 36 men). In both NAA and HAA, significant increases of density and loss of volume were seen in areas of severely increased ventilation (C4) at baseline compared to areas of normal ventilation (C2, p < 0.001). In HAA, morphological changes were more heterogeneous compared to NAA.

Conclusion
Functional CT assessing the extent and distribution of lung parenchyma with pathologically increased ventilation may serve as an imaging marker to prospectively identify lung parenchyma at risk for developing fibrosis.

Key Points
• Voxelwise correlation of serial CT scans suggests spatial correspondence between increased ventilation at baseline and structural changes at follow-up.
• Regional assessment of pathologically increased ventilation at baseline has the potential to prospectively identify tissue at risk for developing fibrosis.
• Presence and extent of pathologically increased ventilation may serve as an early imaging marker of disease activity.
Hydrolyzable microplastics in soil—low biodegradation but formation of a specific microbial habitat?
Authors: Schöpfer Lion , Schnepf Uwe , Marhan Sven , Brümmer Franz , Kandeler Ellen , Pagel Holger 
Published: March 2022

AbstractMicroplastics (MP, plastic particles between 0.1 and 5000 μm) contaminate agricultural soils through the application of organic fertilizers, sewage sludge, and plastic mulch. MP surfaces and the MP-soil interface provide specific habitats for soil microorganisms—the plastisphere. Microorganisms in the plastisphere may benefit from utilizing MP as a carbon (C) source. Hydrolyzable MP with ester bonds are susceptible to enzymatic depolymerization by hydrolysis. In a microcosm experiment, we investigated MP biodegradation of small and large (< 0.5 mm and 0.5–2 mm respectively), hydrolyzable (a poly(lactic acid)/poly(butylene co-adipate terephthalate) blend, PLA/PBAT) and non-hydrolyzable (low-density polyethylene, LDPE) polymers, and the effects of these MP on microorganisms in dry and wet MP-amended soil. MP affected neither abundance and composition of the main soil microbial groups (fungi, Gram-negative, and Gram-positive bacteria), specific activities of ß-glucosidase, ß-xylosidase, lipase, and phenoloxidase, nor respiration in MP-amended soil. Only large PLA/PBAT particles in dry soil were significantly mineralized (15.4% of initial PLA/PBAT-C after 230 days). PLA/PBAT mineralization coincided with enhanced lipase and ß-glucosidase activities on the surfaces of individual PLA/PBAT particles extracted from the soil after incubation (compared to LDPE and non-incubated PLA/PBAT particles). We detected cracks on the surfaces of PLA/PBAT particles using scanning electron microscopy, indicating initiation of MP biodegradation, presumably due to depolymerization by lipases. Results suggest that the PLA/PBAT plastisphere is a polymer-specific habitat for lipase-producing soil microorganisms. Our study demonstrates that analyzing biogeochemical interactions within polymer-specific plastispheres is essential to assess MP fate and their impacts on microbially driven soil processes.
The importance of the Peritoneal Cancer Index (PCI) to predict surgical outcome after neoadjuvant chemotherapy in advanced ovarian cancer
Authors: Rawert Friederike Luise , Luengas-Würzinger Veronica , Claßen-Gräfin von Spee Sabrina , Baransi Saher , Schuler Esther , Carrizo Katharina , Dizdar Anca , Mallmann Peter , Lampe Björn 
Published: March 2022

Abstract
Purpose
Achieving complete cytoreduction (CCR) is crucial for a patient’s prognosis with advanced epithelial ovarian cancer (EOC). So far, prognostic predictors have failed to predict surgical outcome after neoadjuvant chemotherapy (NACT). In clinical trials, scores were used to predict operability in recurrent ovarian cancer (Harter et al. in N Engl J Med 385(23):2123–2131, 2021) but there is no known prediction score for CCR after NACT. The Peritoneal Cancer Index (PCI) is an established tool to predict surgical outcome in primary setting (Lampe et al. in 25:135–144, 2015). We now examined the predictive power of the PCI to achieve CCR after NACT.

Methods
In this single-center study, the data of patients with advanced stage EOC (FIGO > IIIb) treated between 01/2015 and 12/2020 were analyzed retrospectively. Inclusion criteria were a mandatory staging laparoscopy, a PCI score > 25, and NACT. CT scans were analyzed in blinded fashion according to RECIST criteria (Borgani et al. in 237; 93–99, 2019) Reaction of PCI after NACT was compared with the analysis of radiologic imaging and CA-125 levels.

Results
Three hundred and sixteen patients were screened, 62 were treated with NACT, and 23 were included in our analysis. 87% of cases presented with an FIGO IIIc stadium. The reduction of PCI itself after NACT showed to be the most powerful predictor for achieving CCR. The reduction of the initial PCI score by minimum of 8.5 points was a better predictor for CCR than reaching a PCI < 25. In contrast to data deriving from patients undergoing primary debulking surgery (PDS), we found a PCI of 17, rather than 25, to be a more valuable cut-off for CCR in neoadjuvant-treated patients.

Conclusion
The extend of PCI reduction after NACT is a better predictor for achieving CCR compared with CA125 levels and radiologic imaging. The PCI must be assessed differently in neoadjuvant setting than in a primary situation. CCR was most likely for a post-NACT PCI < 17.
Metastasis in the gallbladder: does literature reflect reality?
Authors: de Bitter Tessa J. J. , Trapman Daan M. , Simmer Femke , Hugen Niek , de Savornin Lohman Elise A. J. , de Reuver Philip R. , Verheij Joanne , Nagtegaal Iris D. , van der Post Rachel S. 
Published: March 2022

Abstract
Background
Metastases to the gallbladder (GBm) are rare and pose a unique diagnostic challenge because they can mimic a second primary tumor. This study aimed to gain insight into the clinicopathological and epidemiological characteristics of GBm.

Methods
A comprehensive literature review was performed (literature cohort) and compared with a nationwide cohort of GBm patients diagnosed between 1999 and 2015 in the Netherlands, collected via two linked registries (population cohort). Overall survival (OS) was estimated by Kaplan–Meier. Hazard ratios were determined by a Cox proportional hazard model.

Results
The literature cohort and population cohort consisted of 225 and 291 patients, respectively. In the literature cohort, melanoma was the most frequent origin (33.8%), while colorectal cancer was the most frequent origin in the population cohort (23.7%). Prognosis was poor with median OS ranging from 6.0 to 22.5 months in the literature and population cohorts, respectively. Age, timing of GBm (synchronous/metachronous) and primary tumor origin were independent prognostic factors for OS.

Discussion
Metastases to the gallbladder are rare and carry a poor prognosis. Differences between both cohorts can be attributable to the biased reporting of tumor types that are more easily recognized as GBm because of distinct histological features.
Human-stool-associated tusavirus (Parvoviridae) in domestic goats and sheep
Authors: Reuter Gábor , Pankovics Péter , László Zoltán , Gáspár Gábor , Hui Alvin , Delwart Eric , Boros Ákos 
Published: March 2022

AbstractIn this study, genetic counterparts of the human-stool-associated tusavirus (subfamily Parvovirinae, family Parvoviridae) with >97% and 95-100% amino acid sequence identity in the parvoviral NS1 and VP1 protein were identified in faecal specimens from domestic goats (Capra hircus) and sheep (Ovis aries) in Hungary. Eleven (17.8%) of the 62 faecal specimens from goats and 12 (25.5%) of the 47 from sheep both from less than 12 months old animals were positive for tusavirus DNA by PCR, while none of the specimens collected from cattle and swine were positive. Thus, it cannot be ruled out that tusavirus infection in humans is of zoonotic origin.
HIV Pre-exposure Prophylaxis Implant Stated Preferences and Priorities: Results of a Discrete Choice Experiment Among Women and Adolescent Girls in Gauteng Province, South Africa
Authors: Little Kristen M. , Flomen Lola , Hanif Homaira , Anderson Sharon M. , Thurman Andrea R. , Clark Meredith R. , Doncel Gustavo F. 
Published: March 2022

AbstractFor adolescent girls (AG) and young women (YW), adherence barriers may limit the effectiveness of daily oral HIV pre-exposure prophylaxis (PrEP). Due to its low-burden and long-lasting product attributes, PrEP implants could remove some of the critical adherence barriers of oral PrEP products for individuals at risk of HIV. To explore stated preferences for a long-acting PrEP implant, we conducted a quantitative survey and discrete choice experiment with AG (ages 15–17), YW (18–34), and female sex workers (FSW; ≥ 18) in Gauteng Province, South Africa. We completed 600 quantitative surveys across the three subgroups of women. Respondents stated preference for an implant that provided longer HIV protection (24 months versus 6 months) and required a single insertion. They stated that they preferred a biodegradable implant that could be removed within 1 month of insertion. Respondents had no preference for a particular insertion location. Overall, 78% of respondents said they would be likely (33%) or very likely (45%) to use a PrEP implant were one available, with the majority (82%) stating preference for a product that would provide dual protection against HIV and unintended pregnancies. To reduce their risk of HIV, AG, YW, and FSW in our survey reported a strong willingness to use long-acting, highly-effective, dissolvable PrEP implants.