bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding patients' views and willingness toward the use of telehealth in a cancer genetics service in Asia
Authors: Sim Jackie , Shaw Tarryn , Li Shao‐Tzu , Courtney Eliza , Yuen Jeanette , Chiang Jianbang , Nazir Maryam , Tan Ryan , Ngeow Joanne
Published: May 2021

Telehealth is a growing field, its pertinence magnified by COVID‐19 causing the accelerated digitalization of the world. Given the significant global demand to provide telehealth services, it is important to explore patient receptiveness toward this alternative service model, particularly from regions where it has yet to be implemented. We conducted a cross‐sectional study to understand the views and willingness of patients toward the use of telehealth for cancer genetic counseling. A survey was completed by 160 patients of the National Cancer Centre Singapore, and descriptive statistics were used to analyze the data. The study found that 95.6% (n = 153/160) of participants did not have prior telehealth experience. Most participants were willing or neutral toward having genetic counseling by phone (n = 114/160, 71.3%) and video (n = 106/160, 66.3%). However, majority prefer in‐person appointments for first (n = 127/160, 79.4%) and follow‐up (n = 97/160, 60.6%) visits over telehealth. Majority agreed that a phone/video consultation would meet most of their needs but voiced concerns regarding privacy and sharing of information (n = 79/160, 49.4% for phone; n = 74/160, 46.3% for video) and whether their emotional needs could be met (n = 61/160, 38.1%). Participants’ age, employment status, income, mode of transportation to the appointment, and whether special arrangements were made to attend the in‐person appointment were associated with receptivity to telehealth genetic counseling (p ≤ .05 for all). This study adds diversity to existing literature and demonstrates that patients from Asia are generally willing and accepting of the use of telehealth in a cancer genetics service. This will help meet increasing global demand of telehealth consultations in the post‐pandemic new norm. Furthermore, it will also provide services for underserved populations and patients requiring urgent testing in a timely manner. Further studies are needed to explore the cost‐effectiveness and fair billing methods, as well as willingness and acceptability of telehealth genetic counseling in post‐COVID times.
Can reducing planning safety margins broaden the inclusion criteria for lung stereotactic ablative body radiotherapy?
Authors: Ghandourh Wsam , Batumalai Vikneswary , Boxer Miriam , Holloway Lois
Published: May 2021

Introduction

Stereotactic ablative body radiotherapy (SABR) is currently indicated for inoperable, early‐stage non‐small cell lung carcinoma (NSCLC). Advancements in image‐guidance technology continue to improve treatment precision and enable reductions in planning safety margins. We investigated the dosimetric benefits of margin reduction, its potential to extend SABR to more NSCLC patients and the factors influencing plan acceptability.

Methods

This retrospective analysis included 61 patients (stage IA–IIIA) treated with conventional radiotherapy. Patients were ineligible for SABR due to tumour size or proximity to organs at risk (OAR). Using Pinnacle auto‐planning, three SABR plans were generated for each patient: a regular planning target volume margin plan, a reduced margin plan (gross tumour volume GTV+3 mm) and a non‐margin plan. Targets were planned to 48Gy/4 or 50Gy/5 fractions depending on location. Plans were compared in terms of target coverage, OAR doses and dosimetric acceptability based on local guidelines. Predictors of acceptability were investigated using logistic regression analysis.

Results

Compared to regular margin plans, both reduced margin and non‐margin plans resulted in significant reductions to almost all dose constraints. Dose conformity was significantly worse in non‐margin plans (P < 0.05) and strongly correlated with targets’ surface area/volume ratio (R2 = 0.9, P < 0.05). 26% of reduced margin plans were acceptable, compared to 54% of non‐margin plans. GTV overlap with OARs significantly affected plan acceptability (OR 0.008, 95% CI 0.001–0.073).

Conclusion

Margin reduction significantly reduced OAR doses enabling acceptable plans to be achieved for patients previously excluded from SABR. Indications for lung SABR may broaden as treatment accuracy continues to improve; further work is needed to identify patients most likely to benefit.
Comparison of MMCFS and SINTEX‐F2 for seasonal prediction of Indian summer monsoon rainfall
Authors: Pradhan Maheswar , Rao Suryachandra A. , Doi Takeshi , Pillai Prasanth A. , Srivastava Ankur , Behera Swadhin
Published: May 2021

A comparison of the Indian summer Monsoon Rainfall (ISMR) in two different coupled models (viz., Scale Interaction Experiment‐Frontier‐F2; SINTEX‐F2, and Monsoon Mission Climate Forecast System; MMCFS) is carried out to ascertain the predictability sources in these models and their strengths and weaknesses. SINTEX‐F2 has a stronger cold sea surface temperature (SST) bias in the central equatorial Pacific, and it simulates mean ISMR better while underestimating the interannual variability of ISMR. On the other hand, MMCFS has warmer SST bias in the tropical Pacific off the equator, simulates a drier mean monsoon, but has a more realistic ISMR interannual variability. Further, the cold SST bias in the central tropical Pacific adversely affects the ability of the SINTEX‐F2 to capture the El Niño–Southern Oscillation (ENSO) related interannual variability and teleconnection patterns with monsoon by shifting it further westward in the tropical Pacific Ocean. The models' skill in simulating various climate indices are compared by considering criteria such as anomaly correlation coefficient (ACC), spread to root mean square error (RMSE) ratio, and signal to noise ratio (SNR). The prediction skill for ISMR in terms of ACC in MMCFS (.53) and SINTEX‐F2 (.45) are comparable for hindcasts initialized in February month. However, RMSE for ISMR from February initial conditions in SINTEX‐F2 (1.43 mm/day) is small compared to MMCFS (2.34 mm/day). A simple multi‐model ensemble prediction system based on MMCFS and SINTEX‐F2 results in better prediction skill in terms of ACC for tropical SST and ISMR. The spread/RMSE ratio for ISMR is similar in both the models but is better for ENSO indices in MMCFS at a longer lead time than in SINTEX‐F2. Considering the SNR as performance criteria, MMCFS has an advantage due to better predictability of SST and vertical wind shear in several parts of the Indo‐Pacific domain.
Recombinant fibroblast growth factor‐18 (sprifermin) enhances microfracture‐induced cartilage healing
Authors: Hendesi Honey , Stewart Suzanne , Gibison Michelle L. , Guehring Hans , Richardson Dean W. , Dodge George R.
Published: May 2021

Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra‐articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures, we performed histological evaluations and gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein in three regions of interest. As secondary outcome measures, we examined animals' lameness, performed arthroscopic, radiographic, and computed tomography (CT) scan imaging and gross morphology assessment. We detected the highest treatment benefit following 100 μg sprifermin treatment. The overall histological assessment showed an improvement in the kissing region, and the expression of constitutive genes showed a concentration‐dependent enhancement, especially in the peri‐lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose‐treatment groups were combined. Our results demonstrated, for the first time, an enhancement on microfracture outcomes following sprifermin treatment suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.
Limb preference impacts single‐leg forward hop limb symmetry index values following ACL reconstruction
Authors: Farmer Brooke , Anderson Dillon , Katsavelis Dimitrios , Bagwell Jennifer J. , Turman Kimberly A. , Grindstaff Terry L.
Published: May 2021

Following anterior cruciate ligament (ACL) reconstruction limb dominance for performing tasks is not considered when making rehabilitation progression decisions. The purpose of this study was to determine if strength and functional outcomes differ between individuals who injured their preferred or nonpreferred jumping limb and to determine if these same outcomes differ between individuals who injured their preferred or nonpreferred limb used to kick a ball. A secondary purpose was to determine the association of quadriceps strength and single‐leg forward hop performance with patient self‐reported function. Forty individuals with ACL reconstruction (age = 20.0 ± 4.6 years, height = 174.2 ± 12.7 cm, mass = 71.2 ± 12.7 kg, time since surgery = 5.3 ± 0.8 months) were included in the study. Primary outcome measures included, International Knee Documentation Committee Subjective Knee Form (IKDC) scores, quadriceps limb symmetry index (LSI) values, and single‐leg forward hop LSI values. Limb preference was defined two ways, kicking a ball and performing a unilateral jump. There were no significant differences between groups based on injury to the preferred limb to kick a ball for any of the outcome variables. Individuals who injured their nonpreferred jumping limb demonstrated significantly (p = 0.05, d = 0.77) lower single‐leg forward hop LSI values (81.1% ± 19.5%) compared to individuals who injured their preferred jumping limb (94.1% ± 12.6%), but demonstrated no differences in IKDC scores or quadriceps LSI values. Quadriceps LSI and single‐leg forward hop LSI explained 73% of the variance in IKDC scores, but quadriceps LSI had the strongest association (r = 0.790). These findings suggests that limb preference influences single forward hop LSI values and should be considered following ACL reconstruction.
Development and validation of an analytical method for quantitative determination of three potentially genotoxic impurities in vildagliptin drug material using HPLC‐MS
Authors: Al‐Sabti Bashar , Harbali Jehad
Published: May 2021

A novel high‐performance liquid chromatography‐mass spectrometry method was developed to determine the quantities of pyridine, 4‐dimethylaminopyridine, andN,N‐dimethylaniline impurities in vildagliptin drug material. These impurities are reactive bases that may be used in synthesis of vildagliptin pharmaceutical ingredients. They are considered as potentially genotoxic impurities since they contain electrophilic functional groups. Therefore, these impurities should be monitored at the allowed limits in vildagliptin. Hence a high‐performance liquid chromatography‐mass spectrometry method was developed to quantify the amounts of these impurities in vildagliptin. The column was KROMASIL CN (250 mm × 3.9 mm, 3.5 μm) in reversed‐phase mode. The mobile phase was a mixture of water–methanol (55:45) containing 2.5 mM ammonium acetate and 0.1% formic acid. The mass spectrometer was used to detect the amounts of impurities using selected ionization monitoring mode atm/z = 80, 122, and 123 for pyridine,N,N‐dimethylaniline, and 4‐dimethylaminopyridine, respectively. The flow rate was 0.5 mL/min. The sensitivity of the method was excellent at levels very less than the allowed limits. The method had excellent linearity in the concentration ranges of limit of quantification–150% of the permitted level with coefficients of determination above 0.9990. The recovery ratios were in the range of 93.70–108.63%. Results showed good linearity, precision, accuracy, sensitivity, selectivity, robustness, and solution stability.
Botulinum toxin for chronic parotid sialadenitis: A case series and systematic review
Authors: Strohl Madeleine P. , Chang Chia‐Fan , Ryan William R. , Chang Jolie L.
Published: May 2021

Objective

To evaluate salivary gland chemodenervation with botulinum toxin in chronic parotid sialadenitis.

Methods

Patients who underwent parotid gland chemodenervation for chronic sialadenitis due to duct stenosis refractory to siaendoscopy were reviewed (case series). Additionally, a systematic review of the literature on botulinum toxin injection for chronic parotid sialadenitis was performed. Inclusion criteria included studies containing original data on botulinum toxin injections in patients with chronic sialadenitis symptoms.

Results

Sialadenitis symptoms from 10 patients with 13 affected parotid glands were examined. All had duct stenosis diagnosed on sialendoscopy, refractory sialadenitis symptoms, and received parotid onabotulinum toxin injection(s) (median dose 65U). Of patients with 3‐month follow‐up, 78% reported significant improvement in symptoms. Mean Chronic Obstructive Sialadenitis Symptoms (COSS) Score improved at 3 months post‐injection (47‐25.9, P = .039) with significant reduction in gland pain frequency and gland swelling severity. No patients had a facial nerve paralysis or increased xerostomia. With the systematic review, 518 abstracts were reviewed and 11 studies met inclusion criteria and included case series or case reports with a total of 40 patients treated with botulinum toxin for chronic parotitis. Thirty‐four out of a total of 35 patients in the studies (97%) reported complete (9, 26%) or partial (25, 71%) improvement in sialadenitis symptoms with minimal complications.

Conclusion

Parotid gland chemodenervation with botulinum toxin is a minimally invasive treatment option for symptomatic chronic sialadenitis refractory to medical treatment or sialendoscopy. Botulinum toxin injections alleviate gland pain and swelling associated with salivary obstruction and provide an alternative to parotidectomy for recurrent sialadenitis.

Level of evidence: 4.
Reproductive Strategy of a Continental Shelf Lane Snapper Population from the Southern Gulf of Mexico
Authors: Trejo-Martínez Jorge , Brulé Thierry , Morales-López Natalia , Colás-Marrufo Teresa , Sánchez-Crespo Manuel
Published: May 2021

Reproductive strategy in snapper seems directly related to whether a population or a species occurs over a continental or insular habitat. Since studies on Lane Snapper Lutjanus synagris reproduction have been mostly focused on populations associated with islands, the purpose of this work was to assess the reproductive strategy of a continental shelf population. Specimens (n = 1,165) sampled in the southern Gulf of Mexico along the northern coast of the Yucatan Peninsula between February 2008 and April 2010 were analyzed through histological examination of gonads. A male-biased overall sex ratio was observed, with females being preponderant in larger size-classes. As expected, the Yucatan population displayed the typical continental pattern of sexual maturity and reproductive seasonality. Percentage of maximum size at first maturity was less than 41% for both females and males, and the species reproduced in shallow waters (7–26-m depth) all along the Yucatan coast, mainly between March and July, with spawning peaks observed in May and July. Lane Snapper exhibit asynchronous oocyte recruitment and batch spawning. Results of this study were compared with reproductive data available from both island and continental Lane Snapper populations. It was observed that Lane Snapper populations do not always conform to the pattern of reproductive seasonality and/or size at sexual maturity with regard to habitat type. This study contributes new information concerning the Lane Snapper’s reproductive strategy with regard to habitat type and depth and offers valuable information for the establishment of management strategies designed for Lane Snapper from the southern Gulf of Mexico.
Combined 23Na and 13C imaging at 3.0 Tesla using a single‐tuned large FOV birdcage coil
Authors: Kaggie Joshua D. , Lanz Titus , McLean Mary A. , Riemer Frank , Schulte Rolf F. , Benjamin Arnold J. V. , Kessler Dimitri A. , Sun Chang , Gilbert Fiona J. , Graves Martin J. , Gallagher Ferdia A.
Published: May 2021

Purpose

An unmet need in carbon‐13 (13C)‐MRI is a transmit system that provides uniform excitation across a large FOV and can accommodate patients of wide‐ranging body habitus. Due to the small difference between the resonant frequencies, sodium‐23 (23Na) coil developments can inform 13C coil design while being simpler to assess due to the higher naturally abundant 23Na signal. Here we present a removable 23Na birdcage, which also allows operation as a 13C abdominal coil.

Methods

We demonstrate a quadrature‐driven 4‐rung 23Na birdcage coil of 50 cm in length for both 23Na and 13C abdominal imaging. The coil transmit efficiencies and maps were compared to a linearly driven 13C Helmholtz‐based (clamshell) coil. SNR was investigated with 23Na and 13C data using an 8‐channel 13C receive array within the 23Na birdcage.

Results

The 23Na birdcage longitudinal FOV was > 40 cm, whereas the 13C clamshell was < 32 cm. The transmit efficiency of the birdcage at the 23Na frequency was 0.65 µT/sqrt(W), similar to the clamshell for 13C. However, the coefficient of variation of 23Na‐ was 16%, nearly half that with the 13C clamshell. The 8‐channel 13C receive array combined with the 23Na birdcage coil generated a greater than twofold increase in 23Na‐SNR from the central abdomen compared with the birdcage alone.

Discussion

This 23Na birdcage coil has a larger FOV and improved uniformity when compared to the widely used clamshell coil design while also providing similar transmit efficiency. The coil has the potential to be used for both 23Na and 13C imaging.
Magnetic resonance angiography and perfusion mapping by arterial spin labeling using Fourier transform–based velocity‐selective pulse trains: Examination on a commercial perfusion phantom
Authors: Xu Feng , Zhu Dan , Fan Hongli , Lu Hanzhang , Liu Dapeng , Li Wenbo , Qin Qin
Published: May 2021

Purpose

Benchmarking of flow and perfusion MR techniques on standardized phantoms can facilitate the use of advanced angiography and perfusion‐mapping techniques across multiple sites, field strength, and vendors. Here, MRA and perfusion mapping by arterial spin labeling (ASL) using Fourier transform (FT)–based velocity‐selective saturation and inversion pulse trains were evaluated on a commercial perfusion phantom.

Methods

The FT velocity‐selective saturation–based MRA and FT velocity‐selective inversion–based ASL perfusion imaging were compared with time‐of‐flight and pseudo‐continuous ASL at 3 T on the perfusion phantom at two controlled flow rates, 175 mL/min and 350 mL/min. Velocity‐selective MRA (VSMRA) and velocity‐selective ASL (VSASL) were each performed with three velocity‐encoding directions: foot–head, left–right, and oblique 45°. The contrast‐to‐noise ratio for MRA scans and perfusion‐weighted signal, as well as labeling efficiency for ASL methods, were quantified.

Results

On this phantom with feeding tubes having only vertical and transverse flow directions, VSMRA and VSASL exhibited the dependence of velocity‐encoding directions. The foot–head‐encoded VSMRA and VSASL generated similar signal contrasts as time of flight and pseudo‐continuous ASL for the two flow rates, respectively. The oblique 45°–encoded VSMRA yielded more uniform contrast‐to‐noise ratio across slices than foot–head and left–right‐encoded VSMRA scans. The oblique 45°–encoded VSASL elevated labeling efficiency from 0.22‐0.68 to 0.82‐0.90 through more uniform labeling of the entire feeding tubes.

Conclusion

Both FT velocity‐selective saturation–based VSMRA and FT velocity‐selective inversion–based VSASL were characterized on a commercial perfusion phantom. Careful selection of velocity‐encoding directions along the major vessels is recommended for their applications in various organs.
Robust RF shimming and small‐tip‐angle multispoke pulse design with finite‐difference regularization
Authors: Paez Adrian , Gu Chunming , Cao Zhipeng
Published: May 2021

Purpose

A new regularizer is proposed for the magnitude least‐squares optimization algorithm, to ensure robust parallel transmit RF shimming and small‐tip‐angle multispoke pulse designs for ultrahigh‐field MRI.

Methods

A finite‐difference regularization term is activated as an additional regularizer in the iterative magnitude‐least‐squares based pulse design algorithm when an unwanted flip angle null distribution is detected. Both simulated and experimental maps from different transmit arrays and different human subjects at 7 T were used to evaluate the proposed algorithm. The algorithm was further demonstrated in experiment with dynamic multislice RF shimming for a single‐shot gradient‐echo EPI for human functional MRI at 7 T.

Results

The proposed finite‐difference regularizer effectively prevented excitation null to be formed for RF shimming and small‐tip‐angle multispoke pulses, and improved the latter with a monotonic trade‐off relationship between flip angle error and RF power. The proposed algorithm was demonstrated to be effective with several head‐array geometries by simulation and with a commercial head array with 12 healthy human subjects by experiment. During a functional MRI scan at 7 T with dynamic RF shimming, the proposed algorithm ensured high image SNR throughout the human brain, compared with near‐complete local signal loss by the conventional magnitude‐least‐squares algorithm.

Conclusion

Using finite‐difference regularization to avoid unwanted solutions, the robustness of RF shimming and small‐tip‐angle multispoke pulse design algorithms are improved, with better flip angle homogeneity and a monotonic trade‐off relationship between flip angle error and RF power.
Management of recent onset tendon‐related pain in a primary contact setting: A survey of practice
Authors: Mitham Kieran , Mallows Adrian , Yeowell Gillian , Littlewood Chris
Published: May 2021

Background

Tendon‐related pain is a common and debilitating condition that affects a wide range of people. To inform future research, it is important to understand healthcare professional's current practice.

Objectives

To describe the practice of First Contact Practitioners (FCPs) and Other Clinicians (OCs) for recent onset tendon pain in a primary contact setting. The secondary aim was to understand if practice differed between the locations of pain.

Design

Cross‐sectional online survey

Method

The online survey asked for responses relating to one scenario of shoulder pain and one of Achilles pain. Except location of pain, the scenarios were identical. Responses were collected over a four‐week period to December 2020. The Chi‐Square test was used to analyse the difference in proportion of responses between FCPs and OCs, and between locations of pain.

Results

118 responses were received. Rotator Cuff Related Shoulder Pain (RCRSP) was preferred by 64/118 (54.2%) for the shoulder scenario. Achilles tendinopathy was the preferred term by 86/103 (83.5%) for the Achilles. FCPs were more likely to advise NSAIDs for both shoulder (p = 0.006) and Achilles (p = 0.046) scenarios than OCs. Amended duties were more likely to be advised for manual workers for the shoulder scenario compared to Achilles (p = <0.0001).

Conclusion

There were similarities in the management of recent onset tendon‐related pain; the majority of respondents recommended against further investigations, steroid injections, and recommended exercise. Understanding whether these approaches are clinically effective requires further investigation.
The relationships between paediatric nurses' social support, job satisfaction and patient adverse events
Authors: Khatatbeh Haitham , Al‐Dwaikat Tariq , Oláh András , Onchonga David , Hammoud Sahar , Amer Faten , Prémusz Viktória , Pakai Annamária
Published: May 2021

Aims

To explore the relationships of family, co‐worker and manager support with paediatric nurses' satisfaction and their perception of adverse events. Furthermore, this study aimed to assess the job satisfaction, social support and the perceived patient adverse events.

Design

This study used a cross‐sectional correlational design.

Methods

A convenient sample of 225 paediatric nurses was selected from nine hospitals in Jordan. Both the Pearson correlations and multiple regression tests were used in the analysis. The study was prepared and is reported according to the STROBE checklist.

Results

Significant and positive correlations were found between paediatric nurses' job satisfaction and the social support they receive. Significant negative correlations were also found between adverse events and both family and manager support. The multiple regression results showed that manager support is a significant negative predictor of both pressure ulcers and patient falls, and family support significantly predicted paediatric nurses' job satisfaction.
Linear Multiselenium Interactions in Dicationic Oligomers of 1,5‐(Diselena)canes: Behavior of Semc σ(mcc‐nee) (6≤mc≤16) Elucidated with QTAIM Dual Functional Analysis
Authors: Hayashi Satoko , Nishide Taro , Nagata Kengo , Nakanishi Waro
Published: May 2021

The intrinsic dynamic and static nature mc center‐ne electron interactions of the σ‐type σ(mcc‐nee) were elucidated for the Se‐Se interactions in dicationic oligomers of Se(CH2CH2CH2)2Se (1 (Se, Se)) [n2+ (Se, Se): n=1–8], especially for mc≥6, where n2+ (Se, Se: n=1–8) are abbreviated by n2+ (n=1–8), respectively. QTAIM dual functional analysis (QTAIM‐DFA) was applied to the interactions. Perturbed structures generated using coordinates derived from the compliance constants (Cii) were employed for QTAIM‐DFA. Each Se‐*‐Se in 12+ and 22+ has the nature of CT‐TBP (trigonal bipyramidal adduct formation through CT) and Cov‐w (weak covalent), respectively, which supply the starting points of the investigations. The asterisk emphasizes the existence of a bond critical point on the interaction. All Se‐*‐Se in 32+ are classified by the regular closed shell (r‐CS) interactions and characterized as CT‐MC (molecular complex formation through CT), which are denoted as r‐CS/CT‐MC, except for the central interaction, of which nature is r‐CS/CT‐TBP. Most interactions in 42+–82+ are r‐CS/t‐HBwc (typical‐HB with covalency) but some are pure‐CS/t‐HBnc (t‐HB with no covalency). The linear Se2n2+ interactions in 22+–82+ seem close to those without any limitations, since the nature of Se‐*‐Se inside and outside of (CH2CH2CH2)2 are very similar with each other. The linear Se2n2+ interactions in 32+–82+ are shown to be analyzed as σ(mcc‐nee: 6≤mc≤16), not by the accumulated σ(3c–4e).
Prostate cancer patient‐derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens
Authors: Servant Raphaëlle , Garioni Michele , Vlajnic Tatjana , Blind Melanie , Pueschel Heike , Müller David C , Zellweger Tobias , Templeton Arnoud J , Garofoli Andrea , Maletti Sina , Piscuoglio Salvatore , Rubin Mark A , Seifert Helge , Rentsch Cyrill A , Bubendorf Lukas , Le Magnen Clémentine
Published: May 2021

Patient‐derived organoids (PDOs) represent promising preclinical models in various tumor types. In the context of prostate cancer (PCa), however, their establishment has been hampered by poor success rates, which impedes their broad use for translational research applications. Along with the necessity to improve culture conditions, there is a need to identify factors influencing outcomes and to determine how to assess success versus failure in organoid generation. In the present study, we report our unbiased efforts to generate PDOs from a cohort of 81 PCa specimens with diverse pathological and clinical features. We comprehensively analyzed histological features of each enrolled sample (Gleason score, tumor content, proliferation index) and correlated them with organoid growth patterns. We identified improved culture conditions favoring the generation of PCa organoids, yet no specific intrinsic tumor feature was broadly associated with sustained organoid growth. In addition, we performed phenotypic and molecular characterization of tumor–organoid pairs using immunohistochemistry, immunofluorescence, fluorescence in situ hybridization, and targeted sequencing. Morphological and immunohistochemical profiles of whole organoids altogether provided a fast readout to identify the most promising ones. Notably, primary samples were associated with an initial take‐rate of 83% (n = 60/72) in culture, with maintenance of cancer cells displaying common PCa alterations, such as PTEN loss and ERG overexpression. These cancer organoids were, however, progressively overgrown by organoids with a benign‐like phenotype. Finally, out of nine metastasis samples, we generated a novel organoid model derived from a hormone‐naïve lung metastasis, which displays alterations in the PI3K/Akt and Wnt/β‐catenin pathways and responds to androgen deprivation. Taken together, our comprehensive study explores determinants of outcome and highlights the opportunities and challenges associated with the establishment of stable tumor organoid lines derived from PCa patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Effects of phonological loop on inferential processing during Chinese text reading: Evidence from a dual‐task paradigm
Authors: Wang Weijuan , Fan Lin , Wang Zhen , Liu Xiaoping , Zhang Sumin
Published: May 2021

The role of working memory (WM) components, such as phonological loop, in online inferential processing has thus far not been empirically examined with a dual‐task paradigm. The current study used an online method to examine the effects of the two components of phonological loop—the articulatory rehearsal device and the phonological store device—on online causal inference generation during Chinese text reading. Eighty‐five Chinese university students read three‐sentence inference and control texts and responded to comprehension questions related to targeted inferences in different reading conditions. The results showed that in the articulatory suppression condition, response times (RTs) for comprehension questions of inference texts were considerably longer, and response errors were significantly higher than those in the normal reading condition, which indicated the effects of the articulatory rehearsal device on readers' online causal inference processes during Chinese text reading. Moreover, RTs for comprehension questions of inference texts in the irrelevant speech condition were significantly shorter than those in the normal reading condition, suggesting effects of the phonological store device on readers' causal inference processes during reading. Taken together, these findings indicate that the articulatory rehearsal device plays an important role in inference processes, but readers allocate more cognitive resources to facilitate the construction of causal relations during text‐based inferential comprehension when function of the phonological store device is impaired.
Elbasvir/grazoprevir administered for 12 weeks via percutaneous endoscopic gastrostomy tube achieves sustained virologic response: A case report and a review of the literature
Authors: Shah Rajeev B. , Garrett Katy L. , Brotherton Amy L. , Noska Amanda J.
Published: May 2021

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first‐line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment‐experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first‐line direct‐acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.
Naphthalimide‐modified dendrimers as efficient and low cytotoxic nucleic acid delivery vectors
Authors: Jia Jingxian , Gao Yongguang , Dang Kai , Guo Xiaosong , Ding Aixiang
Published: May 2021

Poly(amidoamine) (PAMAM) dendrimers have been widely used as nucleic acid delivery vectors. To improve the transfection efficacy, ligands such as amino acid, peptide and lipid are conjugated to the periphery of dendrimers. However, the structures of these ligands are generally flexible, and few reports about rigid‐ligand‐modified dendrimers are reported. In this work, three novel PAMAM dendrimers (G5‐1, G5‐2 and G5‐3) modified with rigid naphthalimide were synthesized as nucleic acid delivery vectors. Magnetic resonance spectroscopy showed that the average numbers of naphthalimide molecules conjugated on the PAMAM periphery in compounds G5‐1, G5‐2 and G5‐3 are 8, 30 and 50, respectively. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay revealed good cytocompatibility of these vectors in multiple cell lines, including MG63, HeLa, HEK293 and MC3T3‐E1 cells, with a cell survival rate of more than 90% in most cases. Among the three dendrimers, G5‐1 with fewer naphthalimide molecules showed stronger RNA binding ability than G5‐2 and G5‐3. G5‐1 also exhibited the best gene silencing efficacy at a dendrimer to miRNA weight ratio of 1:2 in MC3T3‐E1 cells, which is much higher than the commercial transfection agent Lipofectamine 2000 tested under the same conditions. In addition, G5‐1 showed high transfection efficacy in plasmid DNA‐mediated luciferase expression experiments. These results suggest that rigid ligand modification can be developed as a new strategy to design safe and highly efficient nucleic acid delivery vectors. © 2021 Society of Industrial Chemistry.
Heuristic assessment of psychological interventions in schools (HAPI Schools)
Authors: Platt Ian A. , Kannangara Chathurika , Carson Jerome , Tytherleigh Michelle
Published: May 2021

Children spend more time in school than in any other formal setting and, with mental illness in children on the rise, there is more pressure on schools to intervene in student mental health than ever before. In the current study, two phases of semistructured interviews were conducted with school leaders and special educational needs coordinators (Phase 1, N = 23; Phase 2, N = 11), to investigate first‐hand experiences in dealing with student mental illness. Thematic analysis, drawing on Grounded Theory, was used to identify themes. The results identified deprivation as one of the main causes of mental ill‐health in students, with insufficient budgets, inappropriate mental health services, and overly long waiting times as barriers to intervention. Difficulties in identifying appropriate mental health interventions to use in school were also reported. The authors propose a simple four‐point heuristic, for assessing the quality of school‐based mental health interventions to be used by school staff, so that educators can more readily identify appropriate mental health support for their students.
PhenoImage: An open‐source graphical user interface for plant image analysis
Authors: Zhu Feiyu , Saluja Manny , Dharni Jaspinder Singh , Paul Puneet , Sattler Scott E. , Staswick Paul , Walia Harkamal , Yu Hongfeng
Published: May 2021

High‐throughput genotyping coupled with molecular breeding approaches have dramatically accelerated crop improvement programs. More recently, improved plant phenotyping methods have led to a shift from manual measurements to automated platforms with increased scalability and resolution. Considerable effort has also gone into developing large‐scale downstream processing of the imaging datasets derived from high‐throughput phenotyping (HTP) platforms. However, most available tools require some programming skills. We developed PhenoImage, an open‐source graphical user interface (GUI) based cross‐platform solution for HTP image processing intending to make image analysis accessible to users with either little or no programming skills. The open‐source nature provides the possibility to extend its usability to meet user‐specific requirements. The availability of multiple functions and filtering parameters provides flexibility to analyze images from a wide variety of plant species and platforms. PhenoImage can be run on a personal computer as well as on high‐performance computing clusters. To test the efficacy of the application, we analyzed the LemnaTec Imaging system derived red, green, and blue (RGB) color intensity and plant pigmentation‐based fluorescence shoot images from two plant species: sorghum [Sorghum bicolor (L.) Moench] and wheat (Triticum aestivum L.) differing in their physical attributes. In the study, we discuss the development, implementation, and working of the PhenoImage.
Genomic evidence supports an independent history of Levantine and Eurasian grapevines
Authors: Sivan Aviad , Rahimi Oshrit , Lavi Bar , Salmon‐Divon Mali , Weiss Ehud , Drori Elyashiv , Hübner Sariel
Published: May 2021

Societal Impact Statement

Grapevine is a major horticultural crop that has been intertwined with human culture for Millennia. The Levant was an important center of the ancient winemaking industry until the collapse of the Byzantine Empire. Consequently, the identity of the ancient grapevine varieties of the Levant was considered lost. Here, we study the domestication history of Levantine grapevine samples using whole‐genome sequencing data and show that some of the samples are authentic descendants of ancient Levantine varieties and that they conform to an independent lineage. This precious germplasm paves a route to bridge the ancient culture of the Levant and modern grapevine varieties. However, accelerated anthropogenic development in this region poses a threat to sampling locations; thus, additional efforts are urged to explore and conserve grapevine and other crop germplasm collections in the Levant.

The ancient wine varieties of the Levant have inspired beliefs and rituals in human societies. Despite their importance, the original Levantine wine‐grape varieties were considered lost due to cultural turnovers commencing in the 7th century CE, leading to the collapse of a flourishing winemaking industry in this region.

We generated whole‐genome sequence data for a diversity panel of wild and domesticated grapevine accessions. Demographic models, pedigree analysis, and genome scans were conducted to estimate divergence among four distinct groups.

Demographic models designated that the domestication in the Caucasus region predated the emergence of the Levantine varieties and that authentic descendants of ancient varieties are represented among the Levantine accessions. We further explored the pedigree relationship among domesticated grapevines and identified intriguing relationship between the “Chardonnay” variety and Levantine accessions. Genomic scans and genetic load analyses further supported the distinct lineage history of the Levantine and Eurasian accessions.

Tracking the domestication history of crops is challenging especially in a perennial species like grapevine. Although the Levantine varieties represent a distinct genomic background, it remains unclear whether ancient extensive gene‐flow or direct domestication of Levantine wild grapevines has sparked the emergence of the ancient Levantine varieties.
Practical consequences of digital sequence information (DSI) definitions and access and benefit‐sharing scenarios from a plant genebank’s perspective
Authors: Brink Martin , van Hintum Theo
Published: May 2021

Societal Impact Statement

As the world is facing a climate crisis and a growing population, feeding this population is a big challenge. Genebanks, conserving and providing access to genetic resources, and plant breeders, using genetic resources from genebanks to create new varieties, play important roles in meeting this challenge. Before making decisions potentially restricting access to digital sequence information (DSI) on genetic resources, it is therefore important to consider the impact of the decisions on the activities of these actors. In this paper, an analysis is made of DSI definitions and access and benefit‐sharing scenarios in the context of their consequences for genebank management.

It is currently discussed whether the use of digital sequence information (DSI) on genetic resources would need to be subject to access and benefit‐sharing obligations, like the use of genetic resources. In this paper, we analyse the consequences of genebank management of DSI definitions currently considered, and of scenarios proposed for dealing with the access and benefit‐sharing aspects of DSI.

The analysis is based on publicly accessible literature and experiences of and discussions with genebank managers, researchers and experts on genetic resources policies. The key findings are as follows:

the definition of DSI is still disputed and definitions currently considered vary from only the base sequence of genomic DNA to all information associated with genetic resources;

four groups of scenarios proposed for arranging the access and benefit‐sharing aspects of DSI can be distinguished, with these scenarios differing in their benefit‐sharing modalities, technical feasibility, the complexity they generate and thus the ease of access to information and genetic resources;

from a genebank perspective, the scenario generating the lowest complexity and the easiest access to DSI would be preferable.

It is concluded that the multilateral and the free access scenarios seem most beneficial for genebanks, as these scenarios limit the complexity for users and allow easy access and use. We are aware of the political difficulties to arrive at these solutions, but hope this paper will contribute to guiding the discussions in a direction that will be beneficial for genebanks, for users of genebank materials and information, and ultimately for addressing the challenges to present and future food security.
Plasmodium chitinases: revisiting a target of transmission‐blockade against malaria
Authors: Viswanath Vysakh K. , Gore Suraj T. , Valiyaparambil Ashwathi , Mukherjee Subhendhu , Lakshminarasimhan Anirudha
Published: May 2021

Malaria is a life‐threatening disease caused by one of the five species of Plasmodium, among which Plasmodium falciparum cause the deadliest form of the disease. Plasmodium species are dependent on a vertebrate host and a blood‐sucking insect vector to complete their life cycle. Plasmodium chitinases belonging to the GH18 family are secreted inside the mosquito midgut, during the ookinete stage of the parasite. Chitinases mediate the penetration of parasite through the peritrophic membrane, facilitating access to the gut epithelial layer. In this review, we describe Plasmodium chitinases with special emphasis on chitinases from P. falciparum and P. vivax, the representative examples of the short and long forms of this protein. In addition to the chitinase domain, chitinases belonging to the long form contain a pro‐domain and chitin‐binding domain. Amino acid sequence alignment of long and short form chitinase domains reveals multiple positions containing variant residues. A subset of these positions was found to be conserved or invariant within long or short forms, indicating the role of these positions in attributing form‐specific activity. The reported differences in affinities to allosamidin for P. vivax and P. falciparum were predicted to be due to different residues at two amino acid positions, resulting in altered interactions with the inhibitor. Understanding the role of these amino acids in Plasmodium chitinases will help us elucidate the mechanism of catalysis and the mode of inhibition, which will be the key for identification of potent inhibitors or antibodies demonstrating transmission‐blocking activity.
Predictable fold switching by theSARS‐CoV‐2 proteinORF9b
Authors: Porter Lauren L.
Published: May 2021

Extant fold‐switching proteins remodel their secondary structures and change their functions in response to environmental stimuli. These shapeshifting proteins regulate biological processes and are associated with a number of diseases, including tuberculosis, cancer, Alzheimer's, and autoimmune disorders. Thus, predictive methods are needed to identify more fold‐switching proteins, especially since all naturally occurring instances have been discovered by chance. In response to this need, two high‐throughput predictive methods have recently been developed. Here we test them on ORF9b, a newly discovered fold switcher and potential therapeutic target from the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2). Promisingly, both methods correctly indicate that ORF9b switches folds. We then tested the same two methods on ORF9b1, the ORF9b homolog from SARS‐CoV‐1. Again, both methods predict that ORF9b1 switches folds, a finding consistent with experimental binding studies. Together, these results (a) demonstrate that protein fold switching can be predicted using high‐throughput computational approaches and (b) suggest that fold switching might be a general characteristic of ORF9b homologs.
Step‐by‐step design of proteins for small molecule interaction: A review on recent milestones
Authors: Pereira José M. , Vieira Maria , Santos Sérgio M.
Published: May 2021

Protein design is the field of synthetic biology that aims at developing de novo custom‐made proteins and peptides for specific applications. Despite exploring an ambitious goal, recent computational advances in both hardware and software technologies have paved the way to high‐throughput screening and detailed design of novel folds and improved functionalities. Modern advances in the field of protein design for small molecule targeting are described in this review, organized in a step‐by‐step fashion: from the conception of a new or upgraded active binding site, to scaffold design, sequence optimization, and experimental expression of the custom protein. In each step, contemporary examples are described, and state‐of‐the‐art software is briefly explored.