bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring linguistic transmission between generations at the scale of individuals
Authors: Thouzeau Valentin , Affholder Antonin , Mennecier Philippe , Verdu Paul , Austerlitz Frédéric
Published: March 2023

Historical linguistics strongly benefited from recent methodological advances inspired by phylogenetics. Nevertheless, no available method uses contemporaneous within-population linguistic diversity to reconstruct the history of human populations. Here, we developed an approach inspired from population genetics to perform historical linguistic inferences from linguistic data sampled at the individual scale, within a population. We built four within-population demographic models of linguistic transmission over generations, each differing by the number of teachers involved during the language acquisition and the relative roles of the teachers. We then compared the simulated data obtained with these models with real contemporaneous linguistic data sampled from Tajik speakers from Central Asia, an area known for its large within-population linguistic diversity, using approximate Bayesian computation methods. Under this statistical framework, we were able to select the models that best explained the data, and infer the best-fitting parameters under the selected models. The selected model assumes that the lexicon of individuals is the result of a vertical transmission by two teachers, with a specific lexicon for each teacher. This demonstrates the feasibility of using contemporaneous within-population linguistic diversity to infer historical features of human cultural evolution.
Development of a collapsed cone convolution/superposition dose calculation algorithm with a mass density-specific water kernel for magnetic resonance-guided radiotherapy
Authors: Ito Kengo , Ishikawa Yojiro , Teramura Satoshi , Kadoya Noriyuki , Katsuta Yoshiyuki , Tanaka Shohei , Takeda Ken , Jingu Keiichi , Yamada Takayuki
Published: March 2023

This study aimed to develop and validate a collapsed cone convolution for magnetic resonance-guided radiotherapy (CCCMR). The 3D energy deposition kernels (EDKs) were generated in water in a 1.5-T transverse magnetic field. The CCCMR corrects the inhomogeneity in simulation geometry by referring to the EDKs according to the mass density between the interaction and energy deposition points in addition to density scaling. Dose distributions in a water phantom and in slab phantoms with inserted inhomogeneities were calculated using the Monte Carlo (MC) and CCCMR. The percentage depth dose (PDD) and off-axis ratio (OAR) were compared, and the gamma passing rate (3%/2 mm) was evaluated. The CCCMR simulated asymmetric dose distributions in the simulation phantoms, especially the water phantom, and all PDD and OAR profiles were in good agreement with the findings of the MC. The gamma passing rates were >99% for each field size and for the entire region. In the inhomogeneity phantoms, although the CCCMR underestimated dose in the low mass density regions, it could reconstruct dose changes at mass density boundaries. The gamma passing rate for the entire region was >95% for the field size of 2 × 2 cm2, but it was 68.9–86.7% for the field sizes of ≥5 × 5 cm2. Conclusively, in water, the CCCMR can obtain dose distributions comparable to those with the MC. Although the dose differences between them were mainly in inhomogeneity regions, the possibility of the effective use of the CCCMR in small field sizes was demonstrated.
Left diaphragmatic hernia after a mild blunt trauma in Syria: a case report
Authors: Soqia Jameel , Ataya Jamal , Alhadid Salem Algomaa , Kakaje Ameer , Chaban Hussain
Published: March 2023

Left side traumatic diaphragmatic hernias (DH) are very rare and usually present acutely. They might represent after years of minor trauma, and they should be considered among differentials to avoid complications. We present a 28-year-old female coming with acute epigastric pain radiating into the chest with dyspnea and vomiting. Her history was negative for trauma and other than very minor trauma two years earlier. Chest X-ray showed atelectasis with mild pleural effusion. Computed tomography scan showed several cavities, filling the left chest with a gaseous liquid level. Surgery was performed that demonstrated DH and the abdominal viscera were returned to the abdomen without any complications. Traumatic DHs can be easily overlooked with the absent of recent major trauma. They can represent years after the original trauma with acute symptoms, which can make it hard to diagnosis if not considered.
Abdominal cocoon syndrome, a diagnostic challenge affecting the treatment. A rare case report from Somalia
Authors: Mahmoud Schauki , Salad Abdurrahman Hashi , Abdullahi Aisha Abdirahman
Published: March 2023

Abdominal cocoon syndrome is defined as idiopathic encapsulation of the bowel within a fibrocollagenous membrane and is considered as a rare cause of small bowel obstruction. A 15-year-old female presented complaining of right lower abdominal pain, distension and vomiting for 24 hours with previous similar attacks in the last four years. She had no another significant medical or surgical history. Computed tomography study revealed matted mildly distended bowel loops centrally with a suspicion of acute appendicitis. Next day, abdominal pain was the only clinical finding and acute appendicitis was the primary diagnosis. During surgery, most of the small bowel was found to be encapsulated within a cocoon-like fibrous membrane. The appendix was congested. Appendectomy, full resection of the membrane and dense adhesiolysis were performed. Herein, we will present the first reported case from Somalia and discuss the radiological findings affecting the management for such a rare disease.
An uncommon midfoot injury, naviculocuneiform and calcaneocuboid fracture dislocation: a case report
Authors: Kamakura Fuminori , Yasuda Gaku , Ishigaki Yoshimasa , Goto Satoshi
Published: March 2023

A 57-year-old man fell from a height of 6 m and injured his right foot. Imaging studies showed an uncommon injury; naviculocuneiform and calcaneocuboid joint fracture dislocations. He underwent a temporary fixation with Kirschner wires (K-wires), and the injured foot was immobilized with a below-knee splint. Weight-bearing was started gradually. The K-wires were removed at 8 weeks. Full weight-bearing was achieved 14 weeks after the operation. At 19 weeks, he returned to his carpentry job. At 1 year, he had no marked limitation of daily activities. Early recognition of these injuries is required to prevent persistent foot pain and long-term dysfunction.
Understanding the sexual health perceptions, concerns, and needs of female partners of prostate cancer survivors
Authors: Gupta Natasha , Zebib Laura , Wittmann Daniela , Nelson Christian J , Salter Carolyn A , Mulhall John P , Byrne Nataliya , Nolasco Tatiana Sanchez , Loeb Stacy
Published: March 2023

Background

Prostate cancer (PCa) and its treatments can have a significant negative impact on the sexual health of survivors and couples, but few studies have specifically examined the impact of PCa-related sexual dysfunction on female partners of survivors.

Aim

Our objective was to perform a qualitative study to comprehensively characterize female partners’ perceptions of the implications of PCa on their sex lives, as well as partners’ sexual health concerns and unmet needs.

Methods

We conducted semi-structured telephone interviews about sexual health and unmet needs with female partners of PCa survivors recruited from multiple clinical locations and support groups for PCa caregivers from September 2021 to March 2022. Interviews were audio-recorded, transcribed verbatim, and independently coded. Participants were recruited until thematic saturation was achieved.

Outcomes

Outcomes of this study were female partner sexual health concerns and unmet needs.

Results

Among 12 participants, the median age was 65 (range 53 to 81) years, 9 were White, the median time since their partner’s PCa diagnosis was 2.25 years (range 11 months to 20 years), and a majority reported that their partner had undergone radical prostatectomy, radiation, and/or hormonal therapy. Major emergent themes pertained to the significant impact of age- and PCa-related sexual dysfunction on female sexual quality of life, the dyadic nature of sexual dysfunction and recovery, the role of the partner in coping with and adjusting to sexual dysfunction, difficulties communicating about sexual dysfunction in an intimate relationship, a lack of physician-led sexual health counseling and support, and the benefit of peer interactions and proactive information seeking in addressing unmet sexual health needs.

Clinical Implications

Future efforts should continue to explore the impact of PCa on partner sexual health and address unmet needs through sexual health education and support.

Strengths and Limitations

In this study, we identified female partners’ sexual health concerns both related to and independent of PCa survivor sexual health. Limitations include exclusion of male partners of survivors and potential responder bias, as partners who agreed to participate may have experienced more sexual health concerns.

Conclusion

We found that female partners experience PCa-related sexual dysfunction as a couple’s disease, grief due to age- and PCa-related sexual losses, and a lack of physician-led sexual health counseling and information. Our results highlight the importance of including partners of PCa survivors in the sexual recovery process and of developing sexual care programs to address partners’ unmet sexual health needs.
Locating Devotion: Sermon Title Pages and the Early Modern Book Market, 1620–1642
Authors: Evans Catherine R
Published: March 2023

This article considers the place that sermons held in the early modern book market through a quantitative survey of the title pages of sermon-books published in English between 1620 and 1642. Working from an EEBO dataset, this research examines four features of title pages: (a) dating referents, (b) location referents, (c) references to the living or status of the preacher, and (d) whether the books were collections. This research demonstrates that the vast majority of sermon-books declared their place of preaching (74%) and the occasion of their preaching (67%). This article explores how the book-buying public’s interest in novelty and the initial performance of the sermon shaped the use of paratextual material. It proposes that the printed sermon makes the page into a privately accessible space to connect with the publicly experienced communal time of the performed sermon, counteracting the desacralizing effect of the press.
Statistical comparison of time profiles of Forbush decreases associated with coronal mass ejections and streams from coronal holes in solar cycles 23–24
Authors: Melkumyan A A , Belov A V , Shlyk N S , Abunina M A , Abunin A A , Oleneva V A , Yanke V G
Published: March 2023

In this paper, Forbush decrease (FD) profiles are compared for events associated with (i) coronal mass ejections from active regions accompanied by solar flares (AR CMEs), (ii) filament eruptions away from active regions (non-AR CMEs), and (iii) high-speed streams (HSSs) from coronal holes (CHs). FD profiles are described by time parameters that are delayed from an FD onset to the registration of maximum values of cosmic ray (CR) density variations, CR density hourly decrease, CR equatorial anisotropy, solar wind (SW) speed, interplanetary magnetic field (IMF) strength and minimum Dst index. Distributions of these parameters from 1997 to 2020 and within maxima and minima of the last solar cycles (SCs) were compared by statistical methods. The results obtained reveal that statistical properties of the time parameters depend both on the FD source and on the solar activity period. FDs associated with AR CMEs develop even at close values of SW parameters faster than those associated with non-AR CMEs and HSS from CHs. Differences between typical FD profiles for events associated with AR and non-AR CMEs are more significant when the interplanetary disturbance contains a magnetic cloud. The difference between FD profiles for events associated with AR and non-AR CMEs is less distinguishable within maximum SC 24 than within maximum SC 23. For FDs associated with HSS from CHs, the main phase durations and the time delays of maximal SW speed are longer within SC 23–24 minimum, while the time delays of maximal IMF strength differ insignificantly between 23–24 and 24–25 minima.
RXJ0437+00: constraining dark matter with exotic gravitational lenses
Authors: Lagattuta David J , Richard Johan , Ebeling Harald , Basto Quentin , Cerny Catherine , Edge Alastair , Jauzac Mathilde , Mahler Guillaume , Massey Richard
Published: March 2023

We present the first strong-gravitational-lensing analysis of the galaxy cluster RX J0437.1+0043 (RXJ0437; z = 0.285). Newly obtained, deep MUSE observations, Keck/MOSFIRE near-infrared spectroscopy, and Hubble Space Telescope SNAPshot imaging reveal 13 multiply imaged background galaxies, three of them (at z = 1.98, 2.97, and 6.02, respectively) in hyperbolic umbilic (H–U) lensing configurations. The H–U images are located only 20–50 kpc from the cluster centre, i.e. at distances well inside the Einstein radius where images from other lens configurations are demagnified and often unobservable. Extremely rare (only one H–U lens was known previously) these systems are able to constrain the inner slope of the mass distribution – and unlike radial arcs, the presence of H–U configurations is not biased towards shallow cores. The galaxies lensed by RXJ0437 are magnified by factors ranging from 30 to 300 and (in the case of H–U systems) stretched nearly isotropically. Taking advantage of this extreme magnification, we demonstrate how the source galaxies in H–U systems can be used to probe for small-scale (∼109 M⊙) substructures, providing additional insight into the nature of dark matter.
Periodic X-ray sources in the massive globular cluster 47 Tucanae: Evidence for dynamically formed cataclysmic variables
Authors: Bao Tong , Li Zhiyuan , Cheng Zhongqun
Published: March 2023

We present a systematic study of periodic X-ray sources in the massive globular cluster 47 Tuc, utilizing deep archival Chandra observations that resolve the cluster core and recently available eROSITA observations that cover the cluster outskirt. By applying the Gregory-Loredo algorithm, we detect 20 periodic signals among 18 X-ray sources, ranging between 205–95731 s. Fourteen periods are newly discovered in the X-ray band. We classify these periodic sources into four quiescent low-mass X-ray binaries, 1 ms pulsar, two coronally-active binaries, and eleven cataclysmic variables (CVs) based on their X-ray temporal and spectral properties, as well as multiband information. Despite a small sample subject to potential selection bias against faint and non-magnetic CVs, the 11 CVs together define an orbital period distribution significantly different from that of the CVs previously found in the solar neighbourhood and the Galactic bulge. In particular, there exists in 47 Tuc an apparent paucity of short-period CVs below the period gap, which might be attributed to a high occupation fraction of non-magnetic CVs. Also characteristic of the 47 Tuc CVs are an overabundance of long-period CVs with a subgiant donor, a substantial fraction of CVs within the period gap, and a steep radial surface density profile. These are best understood as a group of CVs having recently formed via dynamical interactions in the dense cluster core. Despite sufficient sensitivity of the X-ray data, only one periodic source is found between one-third of the half-light radius and the tidal radius, the nature of which is unclear.
Resonant mechanisms that produce near-Sun asteroids
Authors: Toliou Athanasia , Granvik Mikael
Published: March 2023

All near-Earth asteroids (NEAs) that reach sufficiently small perihelion distances will undergo a so-called super-catastrophic disruption. The mechanisms causing such disruptions are currently unknown or, at least, undetermined. To help guide theoretical and experimental work to understand the disruption mechanism, we use numerical simulations of a synthetic NEA population to identify the resonant mechanisms that are responsible for driving NEAs close to the Sun, determine how these different mechanisms relate to their dynamical lifetimes at small heliocentric distances and calculate the average time they spend at different heliocentric distances. Typically, resonances between NEAs and the terrestrial and giant planets are able to dramatically reduce the perihelion distances of the former. We developed an algorithm that scans the orbital evolution of asteroids and automatically identifies occurrences of mean motion and secular resonances. We find that most near-Sun asteroids are pushed to small perihelion distances by the 3:1J and 4:1J mean-motion resonances with Jupiter, as well as the secular resonances ν6, ν5, ν3, and ν4. The time-scale of the small-perihelion evolution is fastest for the 4:1J, followed by the 3:1J, whereas ν5 is the slowest. Approximately 7 per cent of the test asteroids were not trapped in a resonance during the latest stages of their dynamical evolution, which suggests that the secular oscillation of the eccentricity due to the Kozai mechanism, a planetary close encounter, or a resonance that we have not identified pushed them below the estimated average disruption distance.
Constraining atmospheric parameters and surface magnetic fields with ZeeTurbo: an application to SPIRou spectra
Authors: Cristofari P I , Donati J-F , Folsom C P , Masseron T , Fouqué P , Moutou C , Artigau E , Carmona A , Petit P , Delfosse X , Martioli E ,   the SLS consortium
Published: March 2023

We report first results on a method aimed at simultaneously characterizing atmospheric parameters and magnetic properties of M dwarfs from high-resolution near-IR spectra recorded with SPIRou in the framework of the SPIRou Legacy Survey (SLS). Our analysis relies on fitting synthetic spectra computed from marcs model atmospheres to selected spectral lines, both sensitive and insensitive to magnetic fields. We introduce a new code, ZeeTurbo, obtained by including the Zeeman effect and polarized radiative transfer capabilities to Turbospectrum. We compute a grid of synthetic spectra with ZeeTurbo for different magnetic field strengths and develop a process to simultaneously constrain Teff, log g, $\rm {[M/H]}$, $\rm {[\alpha /Fe]}$, and the average surface magnetic flux. In this paper, we present our approach and assess its performance using simulations, before applying it to six targets observed in the context of the SLS, namely AU Mic, EV Lac, AD Leo, CN Leo, PM J18482+0741, and DS Leo. Our method allows us to retrieve atmospheric parameters in good agreement with the literature, and simultaneously yields surface magnetic fluxes in the range 2–4 kG with a typical precision of 0.05 kG, in agreement with literature estimates, and consistent with the saturated dynamo regime in which most of these stars are.
C1q Confers Protection Against Cryptococcal Lung Infection by Alleviating Inflammation and Reducing Cryptococcal Virulence
Authors: Zhao Xu , Shen Lei , Zheng Jianming , Zhu Haiyan , Li Li , Shi Hong , Chen Zhongqing , Li Qian
Published: March 2023

Background

To define the role of C1qa in host defense against Cryptococcus neoformans lung infection, we investigated its susceptibility to cryptococcal lung infection in mice deficient in complement factor C1qa (C1qa−/−).

Methods

We established a wild-type (WT) and C1qa-deficient murine inhalation model with C. neoformans. We compared the host survival rate, inflammatory responses, and pathogenicity of C. neoformans during the infection course between WT and C1qa−/− mice.

Results

The mortality rate of C1qa-deficient mice was significantly higher than that of wild-type mice. The increased formation of Titan cells in the lungs was associated with augmented inflammation in C1qa-deficient mice. The capacity of lung homogenate supernatant from C1qa-deficient mice to induce Titan formation in vitro was greater compared with that of wild-type mice. The C. neoformans isolated from the lungs of infected C1qa-deficient mice was more resistant to macrophage killing in vitro and caused significantly higher mortality after administration to mice compared with that isolated from WT mice.

Conclusions

These findings reveal a novel role of C1qa in host defense against C. neoformans infection by regulating host inflammation and pathogen virulence and provide new insight into the C1q-mediated lung environment underlying the transition from yeast to Titan cell.
Neutralizing Antibody Responses After Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 and BA.2.12.1 Infection Do Not Neutralize BA.4 and BA.5 and Can Be Blunted by Nirmatrelvir/Ritonavir Treatment
Authors: Carlin Aaron F , Clark Alex E , Garretson Aaron F , Bray William , Porrachia Magali , Santos AsherLev T , Rana Tariq M , Chaillon Antoine , Smith Davey M
Published: March 2023

The factors contributing to the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.4 and BA.5 subvariants in populations that experienced recent surges of BA.2 and BA.2.12.1 infections are not understood. Neutralizing antibodies (NAbs) are likely to protect against severe disease if present in sufficient quantity. We found that after BA.2 or BA.2.12.1 infection, NAb responses were largely cross-neutralizing but were much less effective against BA.5. In addition, individuals who were infected and treated early with nirmatrelvir/ritonavir (Paxlovid) had lower NAb levels than untreated individuals.
Coronavirus Disease 2019–Associated Pulmonary Aspergillosis: A Noninvasive Screening Model for Additional Diagnostics
Authors: Permpalung Nitipong , Chiang Teresa Po-Yu , Avery Robin K , Ostrander Darin , Datta Kausik , Segev Dorry L , Durand Christine M , Zhang Sean X , Massie Allan B , Marr Kieren A
Published: March 2023

Background

Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is likely underdiagnosed, and current diagnostic tools are either invasive or insensitive.

Methods

A retrospective study of mechanically ventilated patients with COVID-19 admitted to 5 Johns Hopkins hospitals between March 2020 and June 2021 was performed. Multivariable logistic regression was used for the CAPA prediction model building. Performance of the model was assessed using the area under the receiver operating characteristic curve (AUC).

Results

In the cohort of 832 patients, 98 (11.8%) met criteria for CAPA. Age, time since intubation, dexamethasone for COVID-19 treatment, underlying pulmonary circulatory diseases, human immunodeficiency virus, multiple myeloma, cancer, or hematologic malignancies were statistically significantly associated with CAPA and were included in the CAPA prediction model, which showed an AUC of 0.75 (95% confidence interval, .70–.80). At a screening cutoff of ≥0.085, it had a sensitivity of 82%, a specificity of 51%, a positive predictive value of 18.6%, and a negative predictive value of 95.3%. (The CAPA screening score calculator is available at www.transplantmodels.com).

Conclusions

We developed a CAPA risk score as a noninvasive tool to aid in CAPA screening for patients with severe COVID-19. Our score will also identify a group of patients who are unlikely to have CAPA and who therefore need not undergo additional diagnostics and/or empiric antifungal therapy.
Ixazomib, Oral Metronomic Cyclophosphamide, and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study
Authors: Pelcovits Ari , Barth Peter , Reagan John L , Olszewski Adam J , Rosati Vallerie , Wood Roxanne , Sturtevant Ashlee , Winer Eric S
Published: March 2023

Background

Newly diagnosed multiple myeloma patients have many available treatment options. While lenalidomide, bortezomib, and dexamethasone (RVD) is the preferred initial treatment for many patients, several other agents may provide similar efficacy with less toxicity and improved ease of administration.

Methods

We evaluated the safety and efficacy of the all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone with the use of metronomic cyclophosphamide dosing in the treatment of patients with newly diagnosed multiple myeloma.

Results

The study was stopped prior to planned enrollment due to slow recruitment, with 12 patients available for final analysis. The overall response rate was 58.3% with 2 patients achieving a very good partial response (16.7%) and 5 patients achieving a partial response (41.7%). Median progression-free survival was 16 months, and median overall survival was 43 months. There were no episodes of grade 3 or greater peripheral neuropathy. Grade 3 or greater dermatologic toxicity was experienced in 50% of patients.

Conclusion

Although limited enrollment prevented full efficacy evaluation, our data do not support further study of metronomic cyclophosphamide in combination with ixazomib and dexamethasone in the treatment of newly diagnosed multiple myeloma. The activity of this regimen in the relapsed/refractory setting requires further study (ClinicalTrials.gov Identifier: NCT02412228).
The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer
Authors: O’Neil Daniel S , Ayeni Oluwatosin A , Farrow Hayley A , Chen Wenlong Carl , Demetriou Georgia , Buccimazza Ines , Čačala Sharon , Stopforth Laura W , Joffe Maureen , Antoni Michael H , Lopes Gilberto , Pumpalova Yoanna S , Mapanga Witness , Jacobson Judith S , Crew Katherine D , Neugut Alfred I , Ruff Paul , Cubasch Herbert
Published: March 2023

Introduction

In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy.

Materials and Methods

Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients’ medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities.

Results

The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001).

Conclusions

HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.
Precision oncology for children: A primer for paediatricians
Authors: Cohen-Gogo Sarah , Denburg Avram E , Villani Anita , Thacker Nirav , Egan Grace , Simao Rafael Margarida , Malkin David , Morgenstern Daniel A
Published: March 2023

Cancer is the leading cause of disease-related death in children, adolescents, and young adults beyond the newborn period in North America. Improving survival rates for patients with hard-to-cure cancer remains a challenge. One approach that has gained particular traction is ‘precision oncology’, whereby next-generation sequencing is used to identify genomic or transcriptomic changes that can help clarify the diagnosis, refine prognosis, define an underlying genetic cause, or identify a unique treatment target for a patient’s cancer. In this primer, we provide a brief overview of the evolution of precision paediatric oncology, its current application to clinical oncology practice, and its future potential as a foundational approach to paediatric oncology care in Canada and around the world. We also address the many challenges and limitations inherent to the implementation of precision oncology as the standard of care, including ethical and economic considerations.
Autophagy-Mediated Phosphate Homeostasis in Arabidopsis Involves Modulation of Phosphate Transporters
Authors: Chiu Chang-Yi , Lung Hui-Fang , Chou Wen-Chun , Lin Li-Yen , Chow Hong-Xuan , Kuo Yu-Hao , Chien Pei-Shan , Chiou Tzyy-Jen , Liu Tzu-Yin
Published: March 2023

Autophagy in plants is regulated by diverse signaling cascades in response to environmental changes. Fine-tuning of its activity is critical for the maintenance of cellular homeostasis under basal and stressed conditions. In this study, we compared the Arabidopsis autophagy–related (ATG) system transcriptionally under inorganic phosphate (Pi) deficiency versus nitrogen deficiency and showed that most ATG genes are only moderately upregulated by Pi starvation, with relatively stronger induction of AtATG8f and AtATG8h among the AtATG8 family. We found that Pi shortage increased the formation of GFP-ATG8f-labeled autophagic structures and the autophagic flux in the differential zone of the Arabidopsis root. However, the proteolytic cleavage of GFP-ATG8f and the vacuolar degradation of endogenous ATG8 proteins indicated that Pi limitation does not drastically alter the autophagic flux in the whole roots, implying a cell type–dependent regulation of autophagic activities. At the organismal level, the Arabidopsis atg mutants exhibited decreased shoot Pi concentrations and smaller meristem sizes under Pi sufficiency. Under Pi limitation, these mutants showed enhanced Pi uptake and impaired root cell division and expansion. Despite a reduced steady-state level of several PHOSPHATE TRANSPORTER 1s (PHT1s) in the atg root, cycloheximide treatment analysis suggested that the protein stability of PHT1;1/2/3 is comparable in the Pi-replete wild type and atg5-1. By contrast, the degradation of PHT1;1/2/3 is enhanced in the Pi-deplete atg5-1. Our findings reveal that both basal autophagy and Pi starvation–induced autophagy are required for the maintenance of Pi homeostasis and may modulate the expression of PHT1s through different mechanisms.
Highly tough and elastic microspheric gel for transarterial catheter embolization in treatment of liver metastasis tumor
Authors: Wang Shuyun , Yu Hongjie , Wan Guangsheng , Fang Haowei , Mi Jinxia , Xu Wenqian , Sun Kexiang , Zhang Kunxi , Yin Jingbo , Deng Wanli
Published: March 2023

Transarterial embolization is a widely recognized clinical treatment method for liver tumors. Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency, the present study carries out an attempt of fabricating tough and elastic microspheric gel for promoting embolization efficiency. To promote the toughness of hydrogel, poly(ethylene glycol)-co-poly(ε-caprolactone)-co-poly(ethylene glycol) (PPP) and PPP with two terminal double bonds (PPPDA) are co-assembled into nano-micelles, which are connected with methacrylated chitosan (CSMA) to fabricate microspheric gels via microfluidic technology. Lowering double bond density of micelles promotes the freedom degree of micelles, significantly enhancing hydrogel toughness. To compensate for the strength loss caused by the decrease of double bond density of micelles, phytic acid (PA) are employed to interact with CS to form a physical network, further improving hydrogel strength and toughness. The CS-PPPDA&PPP-PA microspheric gels exhibit higher blocking effect in vitro. A rabbit VX2 liver metastasis tumor model is prepared to verify the embolization efficacy of CS-PPPDA&PPP-PA microspheric gels. Compared with clinical used microspheres, fewer CS-PPPDA&PPP-PA microspheric gels can achieve enough embolization efficiency. After embolization for 14 days, CS-PPPDA&PPP-PA microspheric gels exhibit improved tumor necrosis rate and promoted tumor cells apoptosis with reduced inflammation in surrounding tissues, confirming advanced embolic efficiency of tough microgels.
A real-time system to report abnormal events involving staff in a nuclear medicine therapy unit
Authors: Stendardo Giorgia , Nuccetelli Cristina , Grande Sveva , Palma Alessandra , Venoso Gennaro , Zicari Carmine , Andenna Claudio , Frau Giuseppe , Bonanno Ilaria , Landoni Valeria , Sciuto Rosa , Bruzzaniti Vicente , Cassano Bartolomeo , Iaccarino Giuseppe , Murtas Federica , Canzi Cristina , Zito Felicia , Fattibene Paola
Published: March 2023

A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient’s room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.
Roles and Heterogeneity of Mesenchymal Progenitors in Muscle Homeostasis, Hypertrophy, and Disease
Authors: Fukada So-ichiro , Uezumi Akiyoshi
Published: March 2023

Skeletal muscle is mainly composed of multinucleated cells called myofibers and has excellent regenerative and adaptive abilities. These abilities are granted by muscle satellite cells (MuSCs), which are anatomically defined cells located between myofibers and basal lamina. In addition to myofibers and MuSCs, skeletal muscle contains several types of cells located in interstitial areas, such as mesenchymal progenitors. These cells are positive for platelet-derived growth factor receptor alpha and are called fibro/adipogenic progenitors (FAPs) or mesenchymal stromal cells. Although mesenchymal progenitors were originally identified as the causative cells of ectopic fat accumulation in skeletal muscles, recent studies have shed light on their beneficial roles in homeostasis, regeneration, and hypertrophy. Furthermore, the heterogeneity of mesenchymal progenitors is of great interest in understanding skeletal muscle development, homeostasis, regeneration, aging, and diseases. In this concise review, we summarize recent findings on the physiological roles of mesenchymal progenitors and their heterogeneity and discuss the remaining critical concerns.
The Revised PENIS Score and proposal of the PACKAGE Checklist: a meta-epidemiologic study on penile amputation and replantation
Authors: Tran Aimee A , Machado Bruno L C , Kuykendall Kennedy H , Spencer Horace J , Scherzer Nickolas D , Almajed Wael S , Saghir Norman , Saghir Reyan , Hellstrom Wayne J G
Published: March 2023

Introduction

Penile amputation causes severe physical and psychosocial distress. Microsurgical implementation in penile replantation is presumed to be superior to surgical repair. This assumption has been difficult to verify.

Objectives

The purpose of this study was threefold: (1) to produce an updated review of penile replantation, substantiated by the largest sample size to date; (2) to appraise the comparative value of the novel PENIS Score and propose the PACKAGE Checklist, a guide for standardization of future case reports and reviews; and (3) to improve confusing terminology and recommend the standardization of vocabulary.

Methods

A literature review assessed 432 full-text case reports in 20 languages and identified 123 microsurgical and 40 surgical cases of penile replantation. The novel PENIS Score stratified penile amputations based on 5 criteria: position along the shaft, extension through the penis, neurovascular repair, ischemia time and type, and severed edge condition and contamination. For the outcome measurements, a Kendall tau coefficient evaluated the association between each PENIS criterion for short-term postoperative complications and 3 outcome measures: erection, urination, and sensation.

Results

Less than half of surgical reports on penile replantation are sufficiently detailed to complete all PENIS Score criteria. The viability of microsurgical and surgical replantation was equivalent at 92% and 94%, respectively. A statistically significant correlation was found between microsurgical repair and the return of sensation but not with nerve repair. Return of sensation with nerve repair was 51%, and microsurgical replantation without nerve repair was 42%; both were significantly higher than the 14% for surgical replantation. Preservation of a skin bridge was associated with a 40% reduction in severe postoperative complications.

Conclusion

Microsurgical replantation is superior in return of sensation, with or without nerve repair. Implementing the PACKAGE Checklist and PENIS Score will help inform case reports and reviews.
Profiling mechanisms that drive acute oral toxicity in mammals and its prediction via machine learning
Authors: Wijeyesakere Sanjeeva J , Auernhammer Tyler , Parks Amanda , Wilson Dan
Published: March 2023

We present a mechanistic machine-learning quantitative structure-activity relationship (QSAR) model to predict mammalian acute oral toxicity. We trained our model using a rat acute toxicity database compiled by the US National Toxicology Program. We profiled the database using new and published profilers and identified the most plausible mechanisms that drive high acute toxicity (LD50 ≤ 50 mg/kg; GHS categories 1 or 2). Our QSAR model assigns primary mechanisms to compounds, followed by predicting their acute oral LD50 using a random-forest machine-learning model. These predictions were further refined based on structural and mechanistic read-across to substances within the training set. Our model is optimized for sensitivity and aims to minimize the likelihood of underpredicting the toxicity of assessed compounds. It displays high sensitivity (76.1% or 76.6% for compounds in GHS 1–2 or GHS 1–3 categories, respectively), coupled with ≥73.7% balanced accuracy. We further demonstrate the utility of undertaking a mechanistic approach when predicting the toxicity of compounds acting via a rare mode of action (MOA) (aconitase inhibition). The mechanistic profilers and framework of our QSAR model are route- and toxicity endpoint-agnostic, allowing for future applications to other endpoints and routes of administration. Furthermore, we present a preliminary exploration of the potential role of metabolic clearance in acute toxicity. To the best of our knowledge, this effort represents the first accurate mechanistic QSAR model for acute oral toxicity that combines machine learning with MOA assignment, while also seeking to minimize underprediction of more highly potent substances.
Genome Resource Announcement for Two Isolates of Phytophthora sansomeana with Varying Levels of Pathogenicity on Soybean
Authors: Hebb Linda M. , Poelstra Jelmer W. , Dorrance Anne E.
Published: March 2023

Phytophthora sansomeana was recognized as a distinct species in 2009. It has since been detected in Phytophthora surveys across the North Central region of the United States in recent years. Two isolates of P. sansomeana with moderate and high levels of pathogenicity (Psan_MP and Psan_HP, respectively), based on lesion development on soybean tap roots, were chosen for Oxford Nanopore Technologies long-read genome sequencing to allow within-species genomic comparisons between isolates with different levels of pathogenicity on soybean. The genome assembly size, number of predicted protein-encoding genes, and number of candidate effectors were greater in the highly pathogenic isolate (Psan_HP) than in the moderately pathogenic isolate (Psan_MP). Future work should more closely examine the context of P. sansomeana pathogenicity mechanisms relative to other Phytophthora species.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Acute kidney injury in diabetes mellitus: Epidemiology, diagnostic, and therapeutic concepts
Authors: Gui Yuan , Palanza Zachary , Fu Haiyan , Zhou Dong
Published: March 2023

Acute kidney injury (AKI) and diabetes mellitus (DM) are public health problems that cause a high socioeconomic burden worldwide. In recent years, the landscape of AKI etiology has shifted: Emerging evidence has demonstrated that DM is an independent risk factor for the onset of AKI, while an alternative perspective considers AKI as a bona fide complication of DM. Therefore, it is necessary to systematically characterize the features of AKI in DM. In this review, we summarized the epidemiology of AKI in DM. While focusing on circulation‐ and tissue‐specific microenvironment changes after DM, we described the active cellular and molecular mechanisms of increased kidney susceptibility to AKI under DM stress. We also reviewed the current diagnostic and therapeutic strategies for AKI in DM recommended in the clinic. Updated recognition of the epidemiology, pathophysiology, diagnosis, and medications of AKI in DM is believed to reveal a path to mitigate the frequency of AKI and DM comorbidity that will ultimately improve the quality of life in DM patients.
Myofascial Pain as an Unseen Comorbidity in Osteoarthritis
Authors: Duarte Felipe C.K. , Chien Richard , Ghazinour Golnaz , Murnaghan Kent , West Daniel W.D. , Kumbhare Dinesh A.
Published: March 2023

Objective:

This review aimed to identify, summarize, and appraise the evidence supporting the coexistence of myofascial pain (MPS) and trigger points (MTrP) in osteoarthritis (OA), and the effectiveness of MTrPs treatments in OA-related pain and physical function outcomes.

Methods:

Three databases were searched from inception to June 2022. We included observational and experimental studies to fulfill our 2 study aims. Two independent reviewers conducted 2-phase screening procedures and risk of bias using checklist tools for cross-sectional, quasi-experimental, and randomized control trials. Patient characteristics, findings of active and latent MTrPs in relevant muscles, treatments, and pain and physical function outcomes were extracted from low-risk bias studies.

Results:

The literature search yielded 2898 articles, of which 6 observational and 7 experimental studies had a low bias risk and the data extracted. Active MTrPs in knee OA patients was more evident in the quadriceps and hamstring muscles than in healthy individuals. Dry needling on active MTrPs improved pain and physical function in the short term compared with sham treatment in hip OA patients. In knee OA, dry needling on latent or active MTrPs improved pain and functional outcomes compared with sham needling but did not result in better pain and physical outcomes when combined with a physical exercise program.

Discussion:

The presence of active versus latent MTrPs seems to be a more sensitive discriminating feature of OA given that latent is often present in OA and healthy individuals. Dry needling on active MTrPs improved pain and physical function in the short term compared with sham treatment in hip OA patients. However, the small sample size and the few number of studies limit any firm recommendation on the treatment.

Registry:

The study protocol was prospectively registered in Open Science Framework (https://doi.org/10.17605/OSF.IO/8DVU3).
The effect of HIV on COVID-19 vaccine responses
Authors: Levy Itzchak , Rahav Galia
Published: March 2023

Purpose of review

Persons living with HIV (PLWH) may have a moderately increased risk of morbidity and mortality from COVID-19 infection, especially if viral load is not controlled and if they are immunosuppressed. Vaccination against SARS-CoV-2 is the most effective measure to prevent morbidity and mortality. However, individuals with HIV/AIDS may have less protection after vaccination. The purpose of this review is to summarize some of the recent studies focused on examining the safety, immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines.

Recent findings

The safety of all anti-SARS-CoV-2 vaccines among PLWH is not different from the safety of these vaccines among HIV-negative individuals and is acceptable. PLWH with viral suppression and immune reconstitution (CD4+ cell count > 350 cells/μl) may reach almost same immunogenicity such as people without HIV albeit antibody levels and neutralization may decline more rapidly than in people without HIV. PLWH with viremia or immunosuppressed, especially AIDS, have less immunogenicity.

Full vaccination against SARS-CoV-2 is a well tolerated and efficient way to prevent mortality and morbidity from COVID-19 among PLWH and AIDS patients. It is very important to follow recommended booster vaccination for a continuous and prompt immunogenicity.
Investigating the Anatomic Location of Soft Tissue Fillers in Noninflammatory Nodule Formation: An Ultrasound-Imaging–Based Analysis
Authors: Schelke Leonie W. , Decates Tom S. , Cartier Hugues , Cotofana Sebastian , Velthuis Peter J.
Published: March 2023

INTRODUCTION

Noninflammatory nodules may be persistent to dissolve. To evaluate the possible reasons, a case series of ultrasound images and medical data of patients who were prospectively referred with noninflammatory nodules were evaluated.

MATERIALS AND METHODS

A total of 27 patients with nodules but without signs of inflammation were included. All cases were assessed with an 18-MHz linear ultrasound device. Exact location of the filler material was noted. Relations with clinical data were analyzed using chi-square tests.

RESULTS

Early onset of complaints (<2 weeks) was found in 16 patients and late onset (>2 weeks) in 11. All patients had multiple nodules. In all cases, the filler nodule was found to be located inside the fascia. Extension to the subcutaneous tissue was seen in 8 cases and to the deeper planes in 5. In 14 cases, the filler material was completely located inside layers of the fascia, and migration was observed in 5 cases.

DISCUSSION

Accumulation of filler material in the superficial musculoaponeurotic system or fascia may be an important cause for the occurrence of persistent noninflammatory nodules, either by initial faulty injection technique or by later accumulation through the pathway generated with a needle or cannula. Ultrasound-guided injections are helpful to dissolve the nodule.