bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of antimicrobial use with antimicrobial susceptibility at the calf level in bacteria isolated from the respiratory and digestive tracts of veal calves before slaughter
Authors: Becker Jens , Perreten Vincent , Schüpbach-Regula Gertraud , Stucki Dimitri , Steiner Adrian , Meylan Mireille
Published: August 2022

Objectives

Antimicrobial drugs are frequently administered in veal calves, but investigations on associations with antimicrobial susceptibility of bacteria are scarce and convey partly contradictory findings. The aim of this study was to investigate associations of antimicrobial use (AMU) during the fattening period with antimicrobial susceptibility shortly before slaughter.

Methods

Detailed treatment data of 1905 veal calves from 38 farms were collected prospectively during monthly farm visits for 1 year (n = 1864 treatments, n = 535 visits); 1582 Escherichia coli, 1059 Pasteurella multocida and 315 Mannheimia haemolytica were isolated from rectal and nasopharyngeal swabs collected before slaughter and subjected to antimicrobial susceptibility testing by microdilution. Associations of antimicrobial treatments with resistant isolates were investigated at the calf level.

Results

Associations of AMU with antimicrobial resistance were observed using generalized linear models. For E. coli, the odds of being resistant were increased with increased AMU (OR 1.36 when number of treatments >1, P = 0.066). Use of tetracyclines was associated with resistance to tetracycline (OR 1.86, P < 0.001) and use of penicillins was associated with resistance to ampicillin (OR 1.66, P = 0.014). No significant associations were observed for P. multocida (use of aminoglycosides: OR 3.66 for resistance to spectinomycin, P = 0.074). For M. haemolytica, the odds of being resistant were increased with increased AMU (OR 4.63, P < 0.001), and use of tetracyclines was associated with resistance to tetracycline (OR 6.49, P < 0.001).

Conclusions

Occurrence of resistant bacteria shortly before slaughter was associated with AMU in veal calves. Prudent and appropriate use may contribute to limit the selection of resistant bacteria on veal farms.
The impact of the COVID-19 pandemic on foreign investment and investment arbitration: from energy transition disrupted to the path forward to a greener future
Authors: Arlota Carolina
Published: August 2022

Foreign investment in the energy sector is complex during the best of times. The challenges posed by the COVID-19 pandemic (and its intertwined economic crises) increased competition for foreign investment and strengthened the perennial quest for climate justice. The pandemic added complexity to both domestic and international spheres of governance, which led to calls for a suspension or even a cancellation of arbitration claims involving foreign investments. As developing and developed countries compete for financial resources to transition to a carbon-neutral society, such a suspension or cancellation is of academic and practical interest. Accordingly, this article discusses the impact of the pandemic on foreign investment in the energy sector, focusing on investment claims. It assesses competing views involving the proposed revisions (namely, suspensions and cancellations) and their consequences based on a law and economics perspective. This article also examines how foreign investments that align with the United Nations Sustainable Development Goals may foster the transition to a greener future. Ultimately, this article offers relevant insights that are likely to be applicable to critical future disruptions, whether they occur due to global economic crises or climate-related emergencies.
Dynamic response of photorespiration in fluctuating light environments
Authors: Fu Xinyu , Walker Berkley J
Published: August 2022

Photorespiration is a dynamic process that is intimately linked to photosynthetic carbon assimilation. There is a growing interest in understanding carbon assimilation during dynamic conditions, but the role of photorespiration under such conditions is unclear. In this review, we discuss recent work relevant to the function of photorespiration under dynamic conditions, with a special focus on light transients. This work reveals that photorespiration is a fundamental component of the light induction of assimilation where variable diffusive processes limit CO2 exchange with the atmosphere. Additionally, metabolic interactions between photorespiration and the C3 cycle may help balance fluxes under dynamic light conditions. We further discuss how the energy demands of photorespiration present special challenges to energy balancing during dynamic conditions. We finish the review with an overview of why regulation of photorespiration may be important under dynamic conditions to maintain appropriate fluxes through metabolic pathways related to photorespiration such as nitrogen and one-carbon metabolism.
Adherence to the Dutch Breast Cancer Guidelines for Surveillance in Breast Cancer Survivors: Real-World Data from a Pooled Multicenter Analysis
Authors: Draeger Teresa , Voelkel Vinzenz , Schreuder Kay , Veltman Jeroen , Dassen Anneriet , Strobbe Luc , Heijmans Harald J , Koelemij Ron , Groothuis-Oudshoorn Catharina G M , Siesling Sabine
Published: August 2022

Background

Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce.

Patients and Methods

Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient’s imaging procedures to their demographics, tumor–treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE.

Results

The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings.

Conclusion

Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients’ individual risk profiles for LRR.
COVID-19 and Corporate Finance
Authors: Pagano Marco , Zechner Josef
Published: August 2022

We distill evidence about the effects of COVID-19 on companies. Stock price reactions to the shock differed greatly across firms, depending on their resilience to social distancing, financial flexibility, and corporate culture. The same characteristics affected the response of firms’ sales, employment, and asset growth. Despite the shock, firms expanded their balance sheets and liquidity by raising funds from banks, bonds, and equity markets. While listed firms reduced their leverage, unlisted ones, especially small and medium enterprises, increased it. Government support programs helped firms access external funding. We conclude by identifying unexplored research issues regarding the long-run effects of COVID-19 on companies. (JEL: G11, G12, G13, G21, G24, G28, G32, G33, G35, G38, H81, H84)
Benchmarking Intensity
Authors: Pavlova Anna , Sikorskaya Taisiya
Published: August 2022

Benchmarking incentivizes fund managers to invest a fraction of their funds’ assets in their benchmark indexes, and such demand is inelastic. We construct a measure of inelastic demand a stock attracts, benchmarking intensity (BMI), computed as its cumulative weight in all benchmarks, weighted by assets following each benchmark. Exploiting the Russell 1000/2000 cutoff, we show that changes in stocks’ BMIs instrument for changes in ownership of benchmarked investors. The resultant demand elasticities are low. We document that both active and passive fund managers buy additions to their benchmarks and sell deletions. Finally, an increase in BMI lowers future stock returns.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
The Emergent Power of Human Cellular vs Mouse Models in Translational Hair Research
Authors: Castro Ana Rita , Portinha Carlos , Logarinho Elsa
Published: August 2022

Different animal models have been used for hair research and regeneration studies based on the similarities between animal and human skins. Primary knowledge on hair follicle (HF) biology has arisen from research using mouse models baring spontaneous or genetically engineered mutations. These studies have been crucial for the discovery of genes underlying human hair cycle control and hair loss disorders. Yet, researchers have become increasingly aware that there are distinct architectural and cellular features between the mouse and human HFs, which might limit the translation of findings in the mouse models. Thus, it is enticing to reason that the spotlight on mouse models and the unwillingness to adapt to the human archetype have been hampering the emergence of the long-awaited human hair loss cure. Here, we provide an overview of the major limitations of the mainstream mouse models for human hair loss research, and we underpin a future course of action using human cell bioengineered models and the emergent artificial intelligence.
Enforcement of security rights over seagoing ships, aircraft, and trains in international treaties
Authors: Keijser Thomas , van der Linden van Sprankhuizen Feben
Published: August 2022

This article focuses on the enforcement of security rights over seagoing ships, aircraft, and trains in several international treaties. It contains a largely chronological overview of the relevant international instruments and their scope of application. In addition, this contribution addresses both the conflict-of-laws provisions and the substantive law provisions on the enforcement remedies at the secured creditor's disposal, including procedural aspects of enforcement such as notice requirements, the conditions for a purchaser to obtain ‘clean title’, and de- and reregistration. The comparison of existing rules offers insights for further alignment of the international legal framework for the enforcement of security rights over seagoing ships, aircraft, and trains.
Early Change in Lower Limb Strength and Function in Lung Transplant Patients After Center-Based and Telerehabilitation
Authors: Wickerson Lisa , Rozenberg Dmitry , Singer Lianne G. , Mathur Sunita
Published: August 2022

Purpose:

The aim of this study was to examine the change and relationship among quadriceps torque (QT) and physical function in adult lung transplant (LTx) patients undergoing rehabilitation.

Methods:

A prospective study assessed 6-min walk test (6MWT) distance, QT, and Short Physical Performance Battery (SPPB) at the start of pre-habilitation and 10-12 wk post-LTx. Functional outcomes were examined for within-group differences for participants who completed center-based rehabilitation between September 2019 and March 2020 and participants who completed telerehabilitation (“telerehab”) between March 2020 and June 2021 during COVID-19. Relationships between QT, SPPB, and 6MWT were examined pre- and post-LTx.

Results:

A total of 49 LTx recipients were included (30 men, 61 [56-67] yr, 26 center-based rehab, and 23 telerehab). The 6MWT increased (median 75 m: 95% CI, 35 – 117, P < .0001), and the telerehab group showed an LTx decrease in QT (−9.6 Nm: 95% CI, −29 to −2.3, P = .02) and an increased gait speed (0.21 m/sec: 95% CI, 0.11 – 0.47, P < .0001). Pre-LTx QT showed a moderate correlation to pre-LTx SPPB (r = 0.41, P = .004) and weak correlations to gait speed and 6MWT (r ranging from 0.21 to 0.35, P < .05). Post-LTx QT showed moderate correlations to post-LTx SPPB (r = 0.43, P = .002), gait speed (r = 0.54, P < .001), five-time sit-to-stand (r =−0.57, P < .0001), and 6MWT (r = 0.62, P < .0001).

Conclusions:

Early post-LTx 6MWT and gait speed increased with no improvement in QT or other SPPB components. Correlations between QT and measures of exercise capacity and lower limb function were stronger post-LTx. Serial measurements may further inform functional trajectories and rehabilitation models.
STRUCTURAL OUTCOME AFTER SURGERY FOR STAGE 5 RETINOPATHY OF PREMATURITY BASED ON THE NEW INTERNATIONAL CLASSIFICATION
Authors: Mano Fukutaro , Iwahashi Chiharu , Kuniyoshi Kazuki , Kusaka Shunji
Published: August 2022

Purpose:

This study investigated the outcomes of vitrectomy for Stage 5 retinopathy of prematurity (ROP) based on the International Classification of Retinopathy of Prematurity third edition, in which Stage 5 ROP is divided into three subgroups.

Methods:

Fifty-four eyes of 34 patients with Stage 5 ROP who underwent vitrectomy between 2004 and 2020 were retrospectively analyzed. Data including sex, gestational age and weight at birth, International Classification of Retinopathy of Prematurity 3 subcategories, perioperative use of intravitreal bevacizumab injection and laser photocoagulation, surgical procedure and complications, final retinal reattachment, and follow-up period were collected.

Results:

Complete retinal reattachment was achieved in 16 eyes (88.9%) with Stage 5A and 13 eyes (39.4%) with Stage 5B (P = 0.0003, Wilcoxon rank-sum test). Three patients with Stage 5C were considered inoperable. Postoperative anatomical failure was significantly associated with stage (Stage 5B vs. 5A; odds ratio, 17.986; 95% confidence interval, 3.712–148.502; P = 0.0001, multivariate logistic regression analysis). Intraoperative intravitreal bevacizumab was significantly associated with lower postoperative incidence of vitreous hemorrhage and glaucoma (P = 0.041, chi-square test).

Conclusion:

Staging of preoperative anatomical features based on International Classification of Retinopathy of Prematurity 3 is a useful predictor for final anatomical success. Intraoperative intravitreal bevacizumab might reduce postoperative complication risks.
LOCATIONAL AGREEMENT OF NEAR-INFRARED AUTOFLUORESCENCE WITH CHOROIDAL VASCULAR HYPERPERMEABILITY IN CENTRAL SEROUS CHORIORETINOPATHY
Authors: Azuma Keiko , Nomura Yoko , Kitamoto Kohdai , Hashimoto Yohei , Fujino Ryosuke , Ueda Kohei , Inoue Tatsuya , Obata Ryo
Published: August 2022

Purpose:

To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy, using multimodal imaging and investigate the locational agreement between these findings and CVH.

Methods:

Among patients with central serous chorioretinopathy in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography, spectral-domain optical coherence tomography, and short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated.

Results:

This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. Fluorescein angiography revealed hyperfluorescent areas in 39% of CVH sites. Optical coherence tomography findings identified 65% of CVH sites, but the overlapping index was 5%. Short-wavelength or near-infrared autofluorescence imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The near-infrared autofluorescent dark dots area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952–0.995]).

Conclusion:

Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results may help investigate the anatomical or locational characteristics of CVH in patients with central serous chorioretinopathy.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHARACTERIZATION OF EVOLVING LESIONS IN FELLOW EYES OF EXUDATIVE TYPE 3 MACULAR NEOVASCULARIZATION PATIENTS
Authors: Sacconi Riccardo , Forte Paolo , Capuano Vittorio , Miere Alexandra , Costanzo Eliana , Tombolini Beatrice , Fantaguzzi Federico , Jung Camille , Parravano Mariacristina , Varano Monica , Souied Eric , Bandello Francesco , Querques Giuseppe
Published: August 2022

Purpose:

To investigate fellow eyes of newly diagnosed unilateral exudative Type 3 (T3) macular neovascularization (MNV) patients by assessing the presence and progression of a preclinical neovascular component during a 3-year follow-up.

Methods:

This is a longitudinal study involving three retinal referral centers. Patients affected by unilateral exudative treatment-naive T3 MNV were enrolled.

Results:

Twenty-four eyes of 24 patients (79 ± 6 years old) were enrolled. Nine eyes (37%) displayed a nonexudative T3 MNV at baseline that developed exudation after a mean of 9 ± 9 months. Fifteen eyes that did not display a nonexudative Type 3 MNV at baseline. Five eyes (21%) did not display neovessels at baseline, but showed a nonexudative T3 after 13 ± 9 months, and exudation after 8 ± 3 months. Five eyes (21%) developed active exudative T3 MNV after 23 ± 9 months, with no detectable nonexudative stage at baseline. Five eyes (21%) did not show MNV, but progressed to geographic atrophy by 36 months of follow-up. Overall, T3 MNV in the fellow eye accounted for 79%, all developing exudation over 3 years of follow-up.

Conclusion:

The occurrence of a nonexudative T3 MNV is a frequent event in the fellow eye of patients newly diagnosed with unilateral exudative T3 MNV and it precedes the development of exudation over 3 years (prevalence of 37% and cumulative incidence of 79%). Optical coherence tomography angiography approach may be used to perform an early diagnosis and treatment of patients with T3 MNV.
Rare Case of Neuroendocrine Tumor of Common Bile Duct Identified With Somatostatin Receptor But Not With Glucose Transporter Imaging
Authors: Mohite Ashish , Shukla Varun , M V Manikandan , Chowdhury Zachariah , Chaturvedi Meenakshi
Published: August 2022

Neuroendocrine tumors (NETs) are heterogeneous group of tumors arising from enterochromaffin cells. Neuroendocrine tumors are most commonly found in bowel and pancreatic tissue. Because of paucity of enterochromaffin cells in biliary tract, NETs of bile duct are very rare. Most of the neoplasms in the extrahepatic bile duct are adenocarcinomas; only 0.2% to 0.3% of NETs arise from the bile duct. Cases reported in the literature of biliary carcinoid are diagnosed postoperatively on histopathologic evaluation. We hereby demonstrate a rare presentation of CBD NET identified preoperatively on somatostatin receptor but not on glucose transporter imaging, confirmed by histopathology and immunohistochemistry to be grade 2 NET (Ki-67, 20%).
FDG PET/CT in Isolated Nasal Cavity Metastasis From Squamous Cell Lung Cancer
Authors: Zhang Jun , Dong Aisheng , Wang Yang
Published: August 2022

Nasal cavity metastasis is rare. We present FDG PET/CT findings in a case with isolated nasal cavity metastasis from squamous cell lung cancer. The nasal cavity tumor invaded the nasal septum and hard palate and showed intense inhomogeneous activity, mimicking a primary malignancy. Knowledge of the atypical manifestations of metastatic lung cancer will be helpful for correct diagnosis.
68Ga-FAPI PET/CT Detected Non–PSMA/FDG-Avid Primary Tumor in De Novo Metastatic Prostate Cancer
Authors: Pang Yizhen , Meng Tinghua , Xu Weizhi , Shang Qihang , Chen Haojun
Published: August 2022

68Ga-labeled PET tracer targeting PSMA is a promising diagnostic approach for staging and restating of prostate cancer (PCa), but cases with clinically relevant PCa and false-negative PSMA PET/CT have been reported. In this case, we reported 68Ga-PSMA, 18F-FDG, and 68Ga-FAPI PET/CT findings in a 65-year-old man with de novo metastatic PCa. 68Ga-FAPI PET/CT detected non–PSMA/FDG-avid primary PCa, consisting with multiparametric MRI findings. The subsequent histopathologic examination confirmed a Gleason 4 + 5 PCa. This case highlighted that 68Ga-FAPI PET/CT may be a useful imaging modality for primary PCa detection and localization.
Comparison of Internal Dosimetry of 18F-PSMA-1007 and 68Ga-PSMA-11-HBED-CC
Authors: Sharma Priya , Watts Ankit , Singh Harmandeep
Published: August 2022

Background

Prostate cancer (PCa) is the most common cancer in men worldwide. Targeting prostate-specific membrane antigen (PSMA) using radiopharmaceuticals has shown promising results for PCa imaging as well as theranostics. 68Ga-based PSMA imaging is limited by production of small quantities by generator, and it has led to quest for cyclotron produced 18F-based PSMA ligands. In the current study, we evaluated the biodistribution and internal dosimetry of 18F-PSMA-1007 and compared it with 68Ga-PSMA-11-HBED-CC.

Materials and Methods

A total of 8 patients with histopathologically proven PCa were included in the study, of whom 4 patients underwent 18F-PSMA-1007, and the other 4 patients underwent 68Ga-PSMA-11-HBED-CC PET/CT. The biodistribution of both tracers was quantified for different organs by computing SUVs. All the patients underwent 5-point serial imaging to compute equivalent dose to essential organs and whole-body effective dose using OLINDA-based dosimetry.

Results

The radiotracer uptake in brain, lacrimal gland, salivary gland, heart, lung, liver, gallbladder, spleen, pancreas, intestine, gluteal muscle, and bone marrow were found to be higher in 18F-PSMA-1007 PET as compared with 68Ga PSMA-11 PET. Kidney and urinary bladder showed higher SUV value on 68Ga-PSMA-11-HBED-CC as compared with 18F-PSMA-1007.

The whole-body effective dose from 18F-PSMA-1007 (1.46E−02 mSv/MBq) was higher than 68Ga-PSMA-11-HBED-CC (1.03E−02 mSv/MBq). The highest mean equivalent dose from 18F-PSMA-1007 was observed in the kidneys (1.48E−01 mGy/MBq), followed by spleen (mean, 1.06E−01 mGy/MBq) and liver (6.80E−02 mGy/MBq), whereas 68Ga-PSMA-11-HBED-CC equivalent dose was maximum in the kidneys (2.13E−01 mGy/MBq), followed by liver (3.03E−02 mGy/MBq), spleen (2.90E−02 mGy/MBq), adrenals (2.67E−02 mGy/MBq), and urinary bladder (1.89E−02 mGy/MBq).

Conclusion

Whole-body effective dose from 18F-PSMA-1007 is higher compared with 68Ga-PSMA-11-HBED-CC. 18F-PSMA-1007 shows lesser urinary bladder clearance compared with 68Ga-PSMA-11-HBED-CC, which can allow better interpretation of prostatic bed without significant radioactive urine interference. 18F-PSMA-1007 is a cyclotron-produced alternative to generator-produced 68Ga-PSMA-11-HBED-CC and can emerge as a good diagnostic surrogate for patients planned for 177Lu-PSMA-617 therapy.
“Hood Sign” in Nuclear Medicine: An Unusual Presentation of Mantle Cell Lymphoma as Detected on FDG PET/CT
Authors: Prakash Anjali , Purandare Nilendu , Shah Sneha , Agrawal Archi , Puranik Ameya , Rangarajan Venkatesh
Published: August 2022

Mantle cell lymphoma is a rare and aggressive non-Hodgkin lymphoma with a high propensity for extranodal involvement, typically seen in the liver, marrow, and gastrointestinal system. Being an FDG-avid disease and a sensitive modality for detecting both nodal and extranodal disease, FDG PET/CT is recommended in the workup of mantle cell lymphoma. We present a rare pattern of cutaneous involvement of the head-neck region in a patient with mantle cell lymphoma, which can be described on FDG PET/CT as a “hood sign.”
Comparison of 18F-DOPA and 18F-DTBZ for PET/CT Imaging of Idiopathic Parkinson Disease
Authors: Shi Xinchong , Yang Yang , Jiang LuLu , Chen Jinhua , Yi Chang , Luo Ganhua , Wu Lei , Chu Jianmin , Wang Jian , Chen Ling , Zhang Xiangsong
Published: August 2022

Objective

The aim of this study was to compare 2 imaging tracers, 18F-DOPA and 18F-DTBZ, for PET/CT imaging in idiopathic Parkinson disease (PD).

Methods

We recruited 32 PD patients and 12 healthy controls in this study. All subjects underwent both 18F-DOPA and 18F-DTBZ PET/CT, and the results were interpreted by visual analysis and semiquantitative analysis (specific uptake ratios [SURs]). A 1-way analysis of variance was used to compare the clinical data and the SURs among the patients at different stages. Regression analysis was performed to analyze the correlation between the SURs and the clinical data.

Results

Among the PD patients, there were 7 patients in Hoehn and Yahr stage I, 14 patients in stage II, and 11 patients in stage III. Linear correlation was found in striatal SURs between the 2 tracers (P < 0.05). In patients of early stages, the striatal SUR decrease percent of 2 tracers had no statistical difference (paired t test, P > 0.05). By initial visual analysis, all the patients were interpreted as positive with 18F-DBTZ (6 unilaterally, 26 bilaterally), and 31 cases were regarded as positive with 18F-DOPA (8 unilaterally, 23 bilaterally). After setting the upper limit of SUR images with the putamen SURs of healthy controls (SURT), all patients were interpreted as positive with both tracers (18F-DTBZ: 5 unilaterally, 27 bilaterally; 18F-DOPA: 4 unilaterally, 28 bilaterally).

Conclusion

18F-DTBZ and 18F-DOPA could reflect the same level of dopaminergic neuron degeneration for PD in early stages, and they have the consistent visual analysis results.
Baseline 18F-FDG PET/CT May Portend the Prognosis of Patients With Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma After First-Line Treatment
Authors: Pan Qingqing , Cao Xinxin , Luo Yaping , Li Jian , Li Fang
Published: August 2022

Purpose

The outcome of patients with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is variable. We aim to study if baseline 18F-FDG PET/CT has some prognostic significance in WM/LPL.

Methods

Thirty-three patients with newly diagnosed WM/LPL who underwent baseline 18F-FDG PET/CT and received active treatment thereafter were recruited in this retrospective study. Semiquantitative indices of baseline 18F-FDG PET/CT were measured as total lesion glycolysis (TLG), metabolic tumor volume (MTV), and SUVmax. The patients were followed up for at least 3 years or until reaching the endpoint, which were defined as progression-free survival (PFS) and the time to next treatment (TTNT).

Results

The overall response rate of the first-line treatment in the recruited patients was 84.8% (28/33). The 3-year PFS and overall survival rates were 56.3% and 89.3%, respectively. Patients with PFS <36 months and TTNT <36 months showed TLG and MTV significantly higher than those with PFS ≥36 months and TTNT ≥36 months (P < 0.05). SUVmax in patients with PFS <36 months was significantly higher than those with PFS ≥36 months (P = 0.033). Receiver operating characteristic analysis demonstrated that cutoff values of TLG >291.28 SUVbw * mL, MTV >108.78 mL, and SUVmax >3.16 were optimal for predicting PFS <36 months. Kaplan-Meier analysis showed that TLG >291.28 SUVbw * mL and MTV >108.78 mL were predictive for shorter PFS (P = 0.003) and TTNT (P = 0.002). In multivariate analysis, TLG >291.28 SUVbw * mL and MTV >108.78 mL were independent predictors for shorter PFS (hazard ratio, 3.06; 95% confidence interval, 1.09–8.57; P = 0.033) and TTNT (hazard ratio, 10.01; 95% confidence interval, 2.56–39.22; P = 0.001).

Conclusions

The metabolic indices of TLG and MTV in baseline 18F-FDG PET/CT were independent prognostic factors to predict PFS and TTNT in patients with WM/LPL.
Respondent Burden and Readability of Patient-Reported Outcome Measures for People With Aphasia
Authors: Engelhoven Amy E. R. , Bislick Lauren , Gray Sara , Pompon Rebecca Hunting
Published: August 2022

Purpose:

Patient-reported outcome measures (PROMs) for persons with aphasia (PWA) are commonly used to measure various outcomes. Persons with aphasia commonly present with language deficits that can likely increase respondent burden. Elements that contribute to respondent burden include readability, design, and formatting methods. The aims of this study were to determine how PROMs for PWA rate in level of respondent burden and on readability levels.

Method:

Irwin's 2012 review of PROMs for PWA was used for inclusion criteria and additional PROMs developed after 2012 were identified. This method resulted in 14 PROMs, which were rated on proposed respondent burden criteria and also underwent a readability analysis.

Results:

Six PROMs achieved a 7 or higher with the proposed 10-point respondent burden measure, indicating lower respondent burden. Eight PROMs met the nationally recommended reading level of sixth grade.

Conclusions:

Results indicated that the several PROMs available for PWA fail to minimize respondent burden.
A Scoping Review of the Relationship Between Nonlinguistic Cognitive Factors and Aphasia Treatment Response
Authors: Diedrichs Victoria A. , Jewell Courtney C. , Harnish Stacy M.
Published: August 2022

Purpose:

The purpose of this article was to explore the extent to which nonlinguistic cognitive factors demonstrate a relationship with aphasia treatment outcomes. To that end, we conducted a scoping review to broadly characterize the state of the literature related to this topic.

Methods:

Reporting guidelines from the PRISMA extension for scoping reviews were used to conduct our study, which queried two common databases used in the health science literature, PubMed and Web of Science. Search terms and eligibility criteria are provided. Results are organized by the four nonlinguistic domains of cognition explored across the included studies (i.e., attention, memory, executive functioning, and visuospatial skills).

Results:

Of 949 unique articles identified from our database searches, 17 articles with 18 distinct studies were included in the final scoping review. Notably, most studies included in the scoping review targeted impairment-based aphasia treatments. Most studies also examined multiple domains of nonlinguistic cognition. A relationship between cognition and poststroke aphasia therapy outcomes was identified in nine of 15 studies addressing executive functioning, four of nine studies examining memory, four of eight studies examining visuospatial skills, and two of five studies exploring attention.

Discussion:

The results among included studies were mixed, with few discernible patterns within each of the four cognitive domains, though it appears that the influence of nonlinguistic cognition may depend on the timing (i.e., immediate vs. delayed post-treatment) and type (i.e., trained vs. untrained, generalized) of aphasia therapy outcomes. Future study designs should address maintenance, by including outcome measures at follow-up, and generalization, by including measures of performance on either untrained stimuli or trained stimuli in untrained contexts. Future work should also strive for larger sample sizes, perhaps through collaborations, or prioritize replicability to produce more reliable conclusions.
Nanoscale engagement and clusterization of Programmed death ligand 1 (PD-L1) in the membrane lipid rafts of Non-Small Cell Lung Cancer cells
Authors: Ruglioni Martina , Civita Simone , Salvadori Tiziano , Cristiani Sofia , Carnicelli Vittoria , Barachini Serena , Petrini Iacopo , Nepita Irene , Castello Marco , Diaspro Alberto , Bianchini Paolo , Storti Barbara , Bizzarri Ranieri , Fogli Stefano , Danesi Romano
Published: August 2022

Programmed death ligand 1 (PD-L1) plays a key role in several human tumors, and it has recently become a crucial target for cancer therapy. Yet, its subtle regulatory roles beside the well characterized immunosuppression in PD-1/PD-L1 immune checkpoint are still obscure and should be strictly related to its molecular properties in different cell settings. In this study we targeted the plasma membrane organization of PD-L1 in a Non-Small Cell Lung Cancer (NSCLC) cell line by a multiscale fluorescence imaging toolbox that included super-resolution microscopy approaches to reach the nanoscale. Our findings revealed for the first time that PD-L1 is prevalently engaged in the cholesterol-enriched “raft” regions of the cell membrane. Clusterization and engagement in membrane rafts may afford novel targets for the immuno-oncology strategies in the framework of NSCLC and, possibly, other tumor types.
Cost-Utility and Cost-Effectiveness Analysis of disease-modifying drugs of Relapsing-Remitting Multiple Sclerosis: A Systematic Review
Authors: gallehzan Nasrin Abulhasanbeigi , Khosravi Majid , Soleimanpour Samira , Hoseini Saeed , Mir Habibeh , Alipour Vahid , Rezapour Aziz
Published: August 2022

Background

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system that is categorized as an immune-mediated inflammatory disease. This study aimed to systematically review the cost-benefit and cost-effectiveness of relapsing-remitting drugs for multiple sclerosis.

Methods

To find related research and articles, articles published in Iranian and international databases by using a combination of MeSH (Medical Subject Headings) terms and based on inclusion and exclusion criteria were searched and reviewed. We included studies that addressed interventions, ICER, per QALY, and those which were published in a journal for different methods of infertility treatment, or a major general journal till 2019.

Results

Out of 1,360 records found, finally, 21 records were included in the research. Ten articles were published in the European continent, six articles in the Americ continent, and finally, five articles in the Asia continent. The most common limitations of published economic evaluation studies were in methodology or presentation of incremental analyses, sensitivity analyses, and discounts. The lowest and highest numerical value of outcome measures were -1,623,918 and 2,297,141.53, resprectively. Furthermore, the lowest and highest numerical value of the cost of disease-modifying drugs of RRMS were $180.67, and $1474840.19, resprectively.

Conclusions

Based on the results of all studies, it can be concluded that for the treatment of patients with AF, care-oriented strategies should be preferred to drug strategies. Also, among the drug strategies with different prescribing methods, oral disease-modifying drugs of RRMS should be preferred to injectable drugs and intravenous infusions.
Temporal evolution of multiday, epileptic functional networks prior to seizure occurrence
Authors: Laiou Petroula , Biondi Andrea , Bruno Elisa , Viana Pedro , Winston Joel S , Rashid Zulqarnain , Ranjan Yatharth , Conde Pauline , Stewart Callum , Sun Shaoxiong , Zhang Yuezhou , Folarin Amos , Dobson Richard JB , Schulze-Bonhage Andreas , Duempelmann Matthias , Richardson Mark P ,   RADAR-Consortium
Published: August 2022

Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify properties of epileptic brain networks. In this study we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed from EEG recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.
Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses
Authors: Xiao Hongkui , Ulmert Isabel , Bach Luisa , Huber Johanna , Narasimhan Hamsa , Kurochkin Ilia , Chang Yinshui , Holst Signe , Mörbe Urs , Zhang Lili , Schlitzer Andreas , Pereira Filipe , Schraml Barbara U. , Baumjohann Dirk , Lahl Katharina
Published: August 2022

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1s and cDC2s, while their lineage identity is preserved. Bcl6-deficient cDC1s are diminished in the periphery but maintain their ability to cross-present antigen to CD8+T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDCs causes a complete loss of Notch2-dependent cDC2s in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity toCitrobacter rodentiumin the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.
Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging inC. elegans
Authors: Hou Xinhao , Xu Mingjing , Zhu Chengming , Gao Jianing , Li Meili , Chen Xiangyang , Sun Cheng , Nashan Björn , Zang Jianye , Guang Shouhong , Feng Xuezhu
Published: August 2022

The chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases. Here, we systematically tagged chromodomain proteins with green fluorescent protein (GFP) using CRISPR/Cas9 technology inC. elegans. By combining ChIP-seq analysis and imaging, we delineated a comprehensive expression and functional map of chromodomain proteins. We then conducted a candidate-based RNAi screening and identified factors that regulate the expression and subcellular localization of the chromodomain proteins. Specifically, we revealed a new H3K9me1/2 reader, CEC-5, both by in vitro biochemistry and in vivo ChIP assays. MET-2, an H3K9me1/2 writer, is required for CEC-5 association with heterochromatin. Both MET-2 and CEC-5 are required for the normal lifespan ofC. elegans. Furthermore, a forward genetic screening identified a conserved Arginine124 of CEC-5’s chromodomain, which was essential for CEC-5’s association with chromatin and life span regulation. Thus, our work will serve as a reference to explore chromodomain functions and regulation inC. elegansand allow potential applications in aging-related human diseases.
LRTK: A platform agnostic toolkit for linked-read analysis of both human genomes and metagenomes
Authors: Yang Chao , Zhang Zhenmiao , Huang Yufen , Xie Xuefeng , Liao Herui , Xiao Jin , Veldsman Werner Pieter , Yin Kejing , Fang Xiaodong , Zhang Lu
Published: August 2022

Linked-read sequencing technologies generate high base quality reads that contain extrapolative information on long-range DNA connectedness. These advantages of linked-read technologies are well known and has been demonstrated in many human genomic and metagenomic studies. However, existing linked-read analysis pipelines (e.g., Long Ranger) were primarily developed to process sequencing data from the human genome and are not suited for analyzing metagenomic sequencing data. Moreover, linked-read analysis pipelines are typically limited to one specific sequencing platform. To address these limitations, we present the Linked-Read ToolKit (LRTK), a unified and versatile toolkit for platform agnostic processing of linked-read sequencing data from both human genomes and metagenomes. LRTK provides functions to perform linked-read simulation, barcode error correction, read cloud assembly, barcode-aware read alignment, reconstruction of long DNA fragments, taxonomic classification and quantification, as well as barcode-assisted genomic variant calling and phasing. LRTK has the ability to process multiple samples automatically, and provides the user with the option to generate reproducible reports during processing of raw sequencing data and at multiple checkpoints throughout downstream analysis. We applied LRTK on two benchmarking and three real linked-read data sets from both the human genome and metagenome. We showcase LRTK’s ability to generate comparative performance results from the preceding benchmark study and to report these results in publication-ready HTML document plots. LRTK provides comprehensive and flexible modules along with an easy-to-use Python-based workflow for processing linked-read sequencing datasets, thereby filling the current gap in the field caused by platform-centric genome-specific linked-read data analysis tools.
Growth arrest ofStaphylococcus aureusinduces daptomycin tolerance via cell wall remodelling
Authors: Ledger Elizabeth V. K. , Edwards Andrew M.
Published: August 2022

Almost all bactericidal drugs require bacterial replication and/or metabolic activity for their killing activity. When these processes are inhibited by bacteriostatic antibiotics, bacterial killing is significantly reduced. One notable exception is the lipopeptide antibiotic daptomycin, which has been reported to efficiently kill non-dividing bacteria. However, these studies employed only brief periods of growth arrest. We found that a bacteriostatic concentration of the protein synthesis inhibitor tetracycline led to a time-dependent induction of daptomycin tolerance inS. aureus, with~100,000-fold increase in survival after 16 h growth arrest relative to exponential phase bacteria. Daptomycin tolerance required glucose and was associated with increased production of the cell wall polymers peptidoglycan and wall-teichoic acids. However, whilst accumulation of peptidoglycan was required for daptomycin tolerance, only a low abundance of wall teichoic acid was necessary. Therefore, whilst tolerance to most antibiotics occurs passively due to a lack of metabolic activity and/or replication, daptomycin tolerance arises via active cell wall remodelling.
TRAIL-induces Src mediated MEK/ERK, SMAD3 and β-catenin signalling in apoptosis resistant NSCLC cells
Authors: de Looff Margot , Heng Win Sen , de Jong Steven , Kruyt Frank A.E.
Published: August 2022

Tumour-necrosis factor related apoptosis-inducing ligand (TRAIL) receptors (TRAIL-R1 and -R2) are appealing therapeutic targets to eradicate tumours specifically via caspase-dependent apoptosis. However, resistance is often observed and TRAIL-R activation can even activate pro-tumorigenic non-canonical signalling pathways. Previously, we found that TRAIL-induced RIPK1-Src-STAT3 signalling was mediating cell migration and invasion in resistant non-small cell lung cancer (NSCLC). Here, the contribution of Src in TRAIL signalling in NSCLC cell lines was further examined. TRAIL sensitive H460 and resistant A549 NSCLC cells showed distinct time-dependent rhTRAIL-induced Src phosphorylation patterns with early activation in A549 cells. Pharmacological Src inhibition as well as shRNA knockdown or CRISPR/CAS9-dependent knockout of Src expression did not alter sensitivity to rhTRAIL-induced apoptosis in both cell lines. Silencing of secondary complex proteins showed that TRADD, but not TRAF2, FADD nor caspase-8, was required for Src activation in A549 cells. Possible mediators of Src-dependent rhTRAIL signalling were identified by Src co-IP-LC-mass spectrometric analyses. In A549 cells the number of Src-interacting proteins increased after rhTRAIL treatment, whereas protein numbers decreased in H460 cells. In rhTRAIL treated A549 cells, Src biding proteins included components of the RAF-MEK1/2-ERK, Wnt and SMAD3 signalling pathways. Functional analyses showed that Src mediated phosphorylation of MEK1/2 and ERK, prevented phosphorylation of SMAD3 and was required for nuclear translocation of ERK and β-catenin in A549 cells. Clonogenic growth of both Src proficient and deficient A549 cells was not affected by rhTRAIL exposure, although Src depletion and MEK1/2 inhibition reduced colony size and numbers significantly. In conclusion, rhTRAIL-induced and Src dependent MEK/ERK, SMAD3 and β-catenin signalling may contribute to the known pro-tumorigenic effects of rhTRAIL in resistant NSCLC cells. However, this needs to be further examined, as well as the potential therapeutic implications of targeting these pathways when combined with TRAIL receptor agonists.
Negative interactions and virulence differences drive the dynamics in multispecies bacterial infections
Authors: Schmitz Désirée A. , Allen Richard C. , Kümmerli Rolf
Published: August 2022

Bacterial infections are often polymicrobial, leading to intricate pathogen-pathogen and pathogen-host interactions. There is increasing interest in studying the molecular basis of pathogen interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model hostGalleria mellonellawith one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that host mortality was always determined by the most virulent species regardless of the number of species and pathogen combinations injected. In certain combinations, the more virulent pathogen simply outgrew the less virulent pathogen. In other combinations, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive associations between a pathogen’s growth inside the host, its competitiveness towards other pathogens, and its virulence. Beyond being generalizable across species combinations, our findings predict that treatments against polymicrobial infections should target the most virulent species to reduce host morbidity, a prediction we validated experimentally.

Importance

There is increasing evidence that polymicrobial infections are common and that host morbidity is impacted by interactions between the co-infecting pathogens. In this study, we infected the larvae of the insect hostGalleria mellonellawith four opportunistic human pathogens as mono or multispecies bacterial infections in all possible combinations and followed host survival and pathogen interactions over time. We discovered that species followed the exact same rank order in terms of their virulence, their growth inside the host, and their competitive ability against co-infecting pathogens. As consequence of this consistent rank order, we found that the most virulent species determines host survival dynamics in mixed infections. Beyond revealing a generalizable predictive pattern for virulence outcomes, our findings also predict that treatments should target the most virulent species in polymicrobial infections, a prediction we validated experimentally.