bluuebunny/crossref_metadata_2025_split huggingface dataset:
Image-Based Deep Neural Network for Individualizing Radiotherapy Dose Is Transportable Across Health Systems
Authors: Randall James , Teo P. Troy , Lou Bin , Shah Jainil , Patel Jyoti , Kamen Ali , Abazeed Mohamed E. 
Published: January 2023

PURPOSE We developed a deep neural network that queries the lung computed tomography–derived feature space to identify radiation sensitivity parameters that can predict treatment failures and hence guide the individualization of radiotherapy dose. In this article, we examine the transportability of this model across health systems. METHODS This multicenter cohort-based registry included 1,120 patients with cancer in the lung treated with stereotactic body radiotherapy. Pretherapy lung computed tomography images from the internal study cohort (n = 849) were input into a multitask deep neural network to generate an image fingerprint score that predicts time to local failure. Deep learning (DL) scores were input into a regression model to derive iGray, an individualized radiation dose estimate that projects a treatment failure probability of < 5% at 24 months. We validated our findings in an external, holdout cohort (n = 271). RESULTS There were substantive differences in the baseline patient characteristics of the two study populations, permitting an assessment of model transportability. In the external cohort, radiation treatments in patients with high DL scores failed at a significantly higher rate with 3-year cumulative incidences of local failure of 28.5% (95% CI, 19.8 to 37.8) versus 10.2% (95% CI, 5.9 to 16.2; hazard ratio, 3.3 [95% CI, 1.74 to 6.49]; P < .001). A model that included DL score alone predicted treatment failures with a concordance index of 0.68 (95% CI, 0.59 to 0.77), which had a similar performance to a nested model derived from within the internal cohort (0.70 [0.64 to 0.75]). External cohort patients with iGray values that exceeded the delivered doses had proportionately higher rates of local failure ( P < .001). CONCLUSION Our results support the development and implementation of new DL-guided treatment guidance tools in the image-replete and highly standardized discipline of radiation oncology.
High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer
Authors: Chervoneva Inna , Peck Amy R. , Sun Yunguang , Yi Misung , Udhane Sameer S. , Langenheim John F. , Girondo Melanie A. , Jorns Julie M. , Chaudhary Lubna N. , Kamaraju Sailaja , Bergom Carmen , Flister Michael J. , Hooke Jeffrey A. , Kovatich Albert J. , Shriver Craig D. , Hu Hai , Palazzo Juan P. , Bibbo Marluce , Hyslop Terry , Nevalainen Marja T. , Pestell Richard G. , Fuchs Serge Y. , Mitchell Edith P. , Rui Hallgeir 
Published: January 2023

PURPOSE T-cell–mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor–positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer. METHODS PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors. RESULTS Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001). CONCLUSION Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.
Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma
Authors: Fagundes Gustavo F C , Freitas-Castro Felipe , Santana Lucas S , Afonso Ana Caroline F , Petenuci Janaina , Funari Mariana F A , Guimaraes Augusto G , Ledesma Felipe L , Pereira Maria Adelaide A , Victor Carolina R , Ferrari Marcela S M , Coelho Fernando M A , Srougi Victor , Tanno Fabio Y , Chambo Jose L , Latronico Ana Claudia , Mendonca Berenice B , Fragoso Maria Candida B V , Hoff Ana O , Almeida Madson Q 
Published: January 2023

Abstract

Context
Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula.

Objective
Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs.

Methods
Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint.

Results
Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P &lt; 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin.

Conclusion
The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.
Complementary and Alternative Medicine for Gliomas: Systematic Review and Critical Appraisal of Current Literature
Authors: Kerezoudis Panagiotis , Kerezoudi Evangelia N. , Choudhry Abdurehman , Himes Benjamin T. , Parney Ian F. 
Published: January 2023

BACKGROUND:
Many patients with glioma and their caregivers seek complementary and alternative medicine (CAM) methods to comfort themselves, cope with cancer medication side effects, and feel they are taking control of their disease.

OBJECTIVE:
To summarize existing evidence on safety and efficacy of CAM treatments for gliomas.

METHODS:
We performed an exhaustive electronic literature search for in vitro, animal, and clinical studies (English language, all years available) on CAM modalities for gliomas.

RESULTS:
A total of 378 studies (315 unique articles) were analyzed. Distribution was as follows: in vitro—274 (73%), animal—77 (20%), and clinical—26 (7%, 2491 patients). Most studies were conducted in China (n = 135, 43%), followed by the United States (n = 62, 20%) and Spain (n = 17, 5%-6%). Resveratrol was the most commonly investigated CAM therapy in the in vitro (n = 62) and in vivo (n = 17) setting. Safety/toxicity was examined in 21% of in vitro (cytotoxic at same dose in 48%), 39% of in vivo (no evidence of organ toxicity), and 50% of clinical studies (adverse events reported in 6). Cytotoxicity was the most frequent end point among in vitro (60%) and animal studies (56%), followed by synergistic action with chemotherapy and inhibition of invasiveness and migration. Finally, 7 of 26 studies found no clinical effect, whereas 5 reported possible impact on progression-free or overall survival, 3 demonstrated decrease or arrest of tumor progression, and 2 showed positive impact on symptoms and quality of life.

CONCLUSION:
These findings will hopefully educate providers and patients and stimulate further research in the field of CAM therapy for gliomas.
The C-terminus of the cargo receptor Erv14 affects COPII vesicle formation and cargo delivery
Authors: Lagunas-Gomez Daniel , Yañez-Dominguez Carolina , Zavala-Padilla Guadalupe , Barlowe Charles , Pantoja Omar 
Published: January 2023

ABSTRACT
The endoplasmic reticulum (ER) is the start site of the secretory pathway, where newly synthesized secreted and membrane proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Little is known about how post-translational modification events regulate packaging of cargo into COPII vesicles. The Saccharomyces cerevisiae protein Erv14, also known as cornichon, belongs to a conserved family of cargo receptors required for the selection and ER export of transmembrane proteins. In this work, we show the importance of a phosphorylation consensus site (S134) at the C-terminus of Erv14. Mimicking phosphorylation of S134 (S134D) prevents the incorporation of Erv14 into COPII vesicles, delays cell growth, exacerbates growth of sec mutants, modifies ER structure and affects localization of several plasma membrane transporters. In contrast, the dephosphorylated mimic (S134A) had less deleterious effects, but still modifies ER structure and slows cell growth. Our results suggest that a possible cycle of phosphorylation and dephosphorylation is important for the correct functioning of Erv14.
Evaporative cooling via panting and its metabolic and water balance costs for lizards in the American Southwest
Authors: Loughran Caleb L. , Wolf Blair O. 
Published: January 2023

ABSTRACT
In lizards there is considerable variation in the ability to dissipate environmental/endogenous heat loads through evaporative cooling via panting, which effects how long lizards can spend exposed to high solar heat loads. We recently described the differing capacities of lizards to depress body temperature (Tb) through evaporative cooling via panting. Here, we link panting and Tb depression with rates of evaporative water loss and its metabolic costs under high heat loads. We used flow-through respirometry to measure evaporative water loss rates and metabolism of 17 lizard species from the American Southwest while simultaneously measuring Tb. We exposed lizards to air temperatures (Ta) ranging from 35°C to their critical thermal maximum (CTmax) while marking the onset of panting. We then estimated pre-panting Q10 values for metabolism to partition increases in metabolism associated with the van't Hoff effect from the mechanical cost of panting with increasing heat loads. We found that evaporative cooling costs substantially varied among species, with panting effort significantly affecting lizards' evaporative capacity. Lizard evaporation rates ranged from 0.32 to 1.5 g H2O h−1, with individuals losing as much as 6% h−1 of body mass while panting. Lizards also experienced an increase of up to 7.9-fold in metabolic rate while panting, although the overall energetic costs of panting remained relatively low compared with evaporative water costs. Across species, there was a significant positive relationship between the overall rate of evaporative heat loss and the maximum Ta–Tb gradient a species could maintain. While evaporative cooling may be an effective mechanism for reducing Tb and extending activity in hot environments for many species, it has significant metabolic and water balance costs that should be considered, as habitats with high environmental heat loads can be especially costly to an animal's water budgets.
The added costs of winter ocean warming for metabolism, arm regeneration and survival in the brittle star Ophionereis schayeri
Authors: Christensen Ana Beardsley , Taylor Georgie , Lamare Miles , Byrne Maria 
Published: January 2023

ABSTRACT
As the climate continues to change, it is not just the magnitude of these changes that is important – equally critical is the timing of these events. Conditions that may be well tolerated at one time can become detrimental if experienced at another, as a result of seasonal acclimation. Temperature is the most critical variable as it affects most aspects of an organism's physiology. To address this, we quantified arm regeneration and respiration in the Australian brittle star Ophionereis schayeri for 10 weeks in response to a +3°C warming (18.5°C, simulating a winter heatwave) compared with ambient winter temperature (15.5°C). The metabolic scaling rate (b=0.635 at 15.5°C and 0.746 at 18.5°C) with respect to size was similar to that of other echinoderms and was not affected by temperature. Elevated temperature resulted in up to a 3-fold increase in respiration and a doubling of regeneration growth; however, mortality was greater (up to 44.2% at 18.5°C), especially in the regenerating brittle stars. Metabolic rate of the brittle stars held at 18.5°C was much higher than expected (Q10≈23) and similar to that of O. schayeri tested in summer, which was near their estimated thermotolerance limits. The additional costs associated with the elevated metabolism and regeneration rates incurred by the unseasonably warm winter temperatures may lead to increased mortality and predation risk.
First sighting of a pelagic seabird entangled in a disposable COVID-19 facemask in the Mediterranean Sea
Authors: KARRIS GEORGIOS , SAVVA IOANNIS , KAKALIS ELEFTHERIOS , BAIRAKTARIDOU KYRIAKI , ESPINOSA CHLOE , SMITH Matthew Stephen , BOTSIDOU PETROULA , MOSCHOUS STAMATIOS , VOULGARIS Marios-Dimitrios , PEPPA ELENI , PANAYIDES PANICOS , HADJISTYLLIS HARIS , IOSIFIDES MARIOS 
Published: January 2023

Seabirds are increasingly recognized as important bio-indicators of marine ecosystems that are useful in assessing environmental disturbance on the marine biota. Over the period 2020-22 and during the first national systematic recording of the sea waters surrounding the Republic of Cyprus, we recorded the spatio-temporal presence, abundance and behaviour of seabirds using the ESAS (European Seabirds At Sea) methodology. Here we present the observation of an accidentally entangled pelagic seabird in COVID-19 material which to the best of our knowledge is the first incident in the Mediterranean Basin. The systematic recording of entangled marine birds in personal protective equipment (PPE) used to prevent COVID-19 transmission worldwide seems to be of crucial importance for one of the most important emerging threats for the conservation of seabirds at global scale.
Synthetic hyperspectral array video database with applications to cross-spectral reconstruction and hyperspectral video coding
Authors: Sippel Frank , Seiler Jürgen , Kaup André 
Published: January 2023

In this paper, a synthetic hyperspectral video database is introduced. Since it is impossible to record ground-truth hyperspectral videos, this database offers the possibility to leverage the evaluation of algorithms in diverse applications. For all scenes, depth maps are provided as well to yield the position of a pixel in all spatial dimensions as well as the reflectance in spectral dimension. Two novel algorithms for two different applications are proposed to prove the diversity of applications that can be addressed by this novel database. First, a cross-spectral image reconstruction algorithm is extended to exploit the temporal correlation between two consecutive frames. The evaluation using this hyperspectral database shows an increase in peak signal-to-noise ratio (PSNR) of up to 5.6 dB dependent on the scene. Second, a hyperspectral video coder is introduced, which extends an existing hyperspectral image coder by exploiting temporal correlation. The evaluation shows rate savings of up to 10% depending on the scene.
Optical transmitter for time-bin encoding quantum key distribution
Authors: Morales Julián , Aparicio M. Guadalupe , Longo Carlos F. , Arrieta Cristian L. , Larotonda Miguel A. 
Published: January 2023

We introduce an electro-optical arrangement that can produce time-bin encoded symbols with the decoy state method over a standard optical fiber in the C-band telecom window. The device consists of a specifically designed pulse pattern generator for pulse production and a field-programmable gate array that controls timing and synchronization. The electrical pulse output drives a sequence of intensity modulators acting on a continuous laser that deliver bursts of weak optical pulse pairs of discrete intensity values. Such a transmitter allows for the generation of all the quantum states needed to implement a discrete variable quantum key distribution (QKD) protocol over a single-mode fiber channel. Symbols are structured in bursts; the minimum relative delay between pulses is 1.25 ns, and the maximum symbol rate within a burst is 200 MHz. We tested the transmitter on simulated optical channels of 7 dB and 14 dB loss, obtaining maximum extractable secure key rates of 3.0 kb/s and 0.57 kb/s, respectively. Time-bin-state parameters such as the symbol rate, pulse separation, and intensity ratio between the signal and decoy states can be easily accessed and changed, allowing the transmitter to adapt to different experimental conditions and contributing to the standardization of QKD implementations.
Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study
Authors: Lindberg B. Fredrik , Nelson Ida , Ranstam Jonas , Riker Donald K. 
Published: January 2023

Background
Previous clinical and in vitro investigations have supported the efficacy of a glycerol throat spray containing cold-adapted cod trypsin (ColdZyme) against respiratory viruses causing the common cold bycreating a protective mucosal barrier shown to deactivate common cold virus in vitro and decrease pharyngeal rhinovirus load.

Methods and findings
This was a double-blind, randomized, parallel-group, placebo-controlled study conducted at 10 German sites to evaluate the efficacy of the medical device ColdZyme, a glycerol mouth spray containing cold-adapted cod trypsin for a naturally occurring common cold versus placebo spray. Adults experiencing a minimum of three common colds during the previous year, but otherwise healthy, were enrolled to begin treatment with the mouth spray or placebo six times daily at first sign of a common cold. Jackson’s symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) quality of life (QoL) domain and a sore throat scale were recorded daily by subjects, as well as any use of allowed rescue treatment.
Between January and April 2019, 701 subjects were enrolled and randomly assigned to the ColdZyme group (n = 351) or the placebo group (n = 350). Of the 701 subjects, 438 (62.5%) subjects developed symptoms typical of common cold, and all 438 started study treatment (n = 220 in the ColdZyme group and n = 218 in the placebo group). The demographic profile of the treatment groups were comparable with 68.1% female and almost all subjects being Caucasian (98.4%). The age ranged between 18 and 70 years with a mean age of 41.3 (±14.4) years.
There were no differences between the groups in primary and major secondary endpoints, however, the assessment using the WURSS-21 QoL domain and Jackson score suggests a slightly faster recovery with ColdZyme as symptoms and complaints affecting the quality of life were shortened by about 1 day. The beneficial effect of ColdZyme was particularly noticeable on the fifth day of the common cold. A positive difference between treatment groups was also seen for the subjects’ assessments of global efficacy of the investigational product A robust safety profile for ColdZyme was demonstrated throughout the study.

Conclusion
The safety and tolerability of ColdZyme have been confirmed in a large study population and further establishes evidence of a faster recovery from common cold symptoms. Early self-diagnosis and early use of ColdZyme mouth spray is a safe alternative for treatment of naturally occurring colds.
Effects of specialist care lower limb orthoses on personal goal attainment and walking ability in adults with neuromuscular disorders
Authors: van Duijnhoven Elza , Koopman Fieke S. , Ploeger Hilde E. , Nollet Frans , Brehm Merel-Anne 
Published: January 2023

Background
Lower limb orthoses intend to improve walking in adults with neuromuscular disorders (NMD). Yet, reported group effects of lower limb orthoses on treatment outcomes have generally been small and heterogeneous. We propose that guideline-based orthotic care within a multidisciplinary expert setting may improve treatment outcomes.

Aim
To examine the effectiveness of specialist care orthoses compared to usual care orthoses on personal goal attainment and walking ability.

Design
Cohort study.

Population
Adults with NMD who experienced walking problems due to calf and/or quadriceps muscle weakness and were provided with a specialist care lower limb orthosis between October 2011 and January 2021.

Methods
Three months after provision, the specialist care orthosis was compared to the usual care orthosis worn at baseline in terms of personal goal attainment (Goal Attainment Scaling (GAS)), comfortable walking speed (m/s), net energy cost (J/kg/m) (both assessed during a 6-minute walk test), perceived walking ability and satisfaction.

Results
Sixty-four adults with NMD were eligible for analysis. The specialist care orthoses comprised 19 dorsiflexion-restricting ankle-foot orthoses (AFOs), 22 stance-control knee-ankle-foot orthoses (KAFOs) and 23 locked KAFOs. Overall, 61% of subjects showed a clinically relevant improvement in GAS score. Perceived safety, stability, intensity, fear of falling and satisfaction while walking all improved (p≤0.002), and subjects were satisfied with their specialist care orthosis and the services provided. Although no effects on walking speed or net energy cost were found in combined orthosis groups, specialist care AFOs significantly reduced net energy cost (by 9.5%) compared to usual care orthoses (from mean (SD) 3.81 (0.97) to 3.45 (0.80) J/kg/m, p = 0.004).

Conclusion
Guideline-based orthotic care within a multidisciplinary expertise setting could improve treatment outcomes in adults with NMD compared to usual orthotic care by improvements in goal attainment and walking ability. A randomized controlled trial is now warranted to confirm these results.