bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of transcranial direct current stimulation (tDCS) to reduce impulsivity and aggression in adults with mild intellectual developmental disabilities: the tDCS-RIADD randomised controlled trial protocol
Authors: Khalifa Najat , Hawken Emily R. , Bickle Andrew , Cabrera Mariel , Heath Travis , Drury Andrew , Jones Jessica , Ayub Muhammad
Published: May 2022

Background

Challenging behaviours, in particular aggressive behaviours, are prevalent among people with intellectual developmental disabilities. Predictors of challenging behaviours are numerous, including past history of aggression, poor coping skills and impulsivity. Factors like motor or rapid-response impulsivity (RRI) have neurobiological underpinnings that may be amenable to change via neuromodulation using non-invasive brain stimulation techniques like transcranial direct current stimulation (tDCS).

Methods

This study aims to determine the efficacy of anodal tDCS in reducing RRI and incidents of aggression in people with intellectual developmental disabilities (IDD) in residential or hospital settings. Using a single blind, randomised, sham-controlled trial design, adults with IDD, with a history of impulsivity leading to aggression, will be randomised to receive either repetitive anodal or sham tDCS applied to the left dorsolateral prefrontal cortex. Outcome measures assessing impulsivity and aggression will be collected for up to 1 month following the last tDCS session.

Discussion

The results of this study may pave the way for developing targeted interventions for impulsivity and aggressive behaviours in people with IDD.
A randomized controlled trial to assess the efficacy of Parenting-STAIR in treating maternal PTSD to reduce maltreatment recidivism: protocol for the Safe Mothers, Safe Children study
Authors: Lindsey Michael , Sullivan Kathrine , Chemtob Claude , Ancharski Kelly , Jaccard James , Cloitre Marylène , Urquiza Anthony , Timmer Susan , Okosi Mercedes , Kaplan Debra
Published: May 2022

Background

Child maltreatment recidivism substantially increases the likelihood of adverse life outcomes, but there is little evidence that family preservation services are effective at reducing recidivism. Mothers in child welfare have very high rates of trauma exposure; maternal post-traumatic stress disorder (PTSD) is an intervention target that has the potential to reduce abuse and neglect. The Safe Mothers, Safe Children (SMSC) intervention program involves the delivery of an innovative combination of interventions, including Skills Training in Affective and Interpersonal Regulation (STAIR) and Parent-Child Interaction Therapy (PCIT). The combined intervention, Parenting-STAIR (P-STAIR), targets maternal PTSD and comorbid depression symptoms to reduce the adverse effects of PTSD on parenting, improve positive parenting skills, and prevent maltreatment recidivism.

Methods

This study is a two-arm randomized controlled trial: P-STAIR (23 sessions) versus supportive counseling (23 sessions). Participants are mothers receiving child welfare family preservation services (FPS), with a child in the age range of 1–8 years old and meeting diagnostic criteria for PTSD (with/without depression). Clinical assessment occurs at pre-treatment (baseline), two in-treatment assessments (mid-assessment #1 after module 9 and mid-assessment #2 after module 15), post-treatment, and at a 6-month follow-up. Recidivism will be measured using the New York State Child Welfare Registry (NYSCWR). We will enroll a total of 220 participants over 4 years: half (N = 110) randomly assigned to the P-STAIR condition and half (N = 110) to the supportive counseling condition.

Discussion

This is the first RCT to investigate the efficacy of P-STAIR. The findings for the trial have the potential to contribute to the expansion of evidence-based practices for maternal PTSD, maltreatment, and child welfare.
Dynamic functional connectivity patterns associated with dementia risk
Authors: Dautricourt Sophie , Gonneaud Julie , Landeau Brigitte , Calhoun Vince D. , de Flores Robin , Poisnel Géraldine , Bougacha Salma , Ourry Valentin , Touron Edelweiss , Kuhn Elizabeth , Demintz-King Harriet , Marchant Natalie L. , Vivien Denis , de la Sayette Vincent , Lutz Antoine , Chételat Gaël ,   for the Medit-Ageing Research Group, Arenaza-Urquijo Eider M. , Allais Florence , André Claire , Asselineau Julien , Bejanin Alexandre , Champetier Pierre , Chételat Gaël , Chocat Anne , Dautricourt Sophie , de Flores Robin , Delarue Marion , Egret Stéphanie , Felisatti Francesca , Devouge Eglantine Ferrand , Frison Eric , Gonneaud Julie , Heidmann Marc , Tran Thien Huong , Kuhn Elizabeth , le Du Gwendoline , Landeau Brigitte , Lefranc Valérie , Lutz Antoine , Mezenge Florence , Moulinet Inès , Ourry Valentin , Palix Cassandre , Paly Léo , Poisnel Géraldine , Quillard Anne , Rauchs Géraldine , Rehel Stéphane , Requier Florence , Touron Edelweiss , Vivien Denis , Ware Caitlin , Lugo Sebastian Baez , Klimecki Olga , Vuilleumier Patrik , Barnhofer Thorsten , Collette Fabienne , Salmon Eric , de la Sayette Vincent , Delamillieure Pascal , Batchelor Martine , Beaugonin Axel , Gheysen Francis , Demnitz-King Harriet , Marchant Natalie , Whitfield Tim , Schimmer Corinne , Wirth Miranka
Published: May 2022

Background

This study assesses the relationships between dynamic functional network connectivity (DFNC) and dementia risk.

Methods

DFNC of the default mode (DMN), salience (SN), and executive control networks was assessed in 127 cognitively unimpaired older adults. Stepwise regressions were performed with dementia risk and protective factors and biomarkers as predictors of DFNC.

Results

Associations were found between times spent in (i) a “weakly connected” state and lower self-reported engagement in early- and mid-life cognitive activity and higher LDL cholesterol; (ii) a “SN-negatively connected” state and higher blood pressure, higher depression score, and lower body mass index (BMI); (iii) a “strongly connected” state and higher self-reported engagement in early-life cognitive activity, Preclinical Alzheimer’s cognitive composite-5 score, and BMI; and (iv) a “DMN-negatively connected” state and higher self-reported engagement in early- and mid-life stimulating activities and lower LDL cholesterol and blood pressure. The lower number of state transitions was associated with lower brain perfusion.

Conclusion

DFNC states are differentially associated with dementia risk and could underlie reserve.
An annotated corpus of clinical trial publications supporting schema-based relational information extraction
Authors: Sanchez-Graillet Olivia , Witte Christian , Grimm Frank , Cimiano Philipp
Published: May 2022

Background

The evidence-based medicine paradigm requires the ability to aggregate and compare outcomes of interventions across different trials. This can be facilitated and partially automatized by information extraction systems. In order to support the development of systems that can extract information from published clinical trials at a fine-grained and comprehensive level to populate a knowledge base, we present a richly annotated corpus at two levels. At the first level, entities that describe components of the PICO elements (e.g., population’s age and pre-conditions, dosage of a treatment, etc.) are annotated. The second level comprises schema-level (i.e., slot-filling templates) annotations corresponding to complex PICO elements and other concepts related to a clinical trial (e.g. the relation between an intervention and an arm, the relation between an outcome and an intervention, etc.).

Results

The final corpus includes 211 annotated clinical trial abstracts with substantial agreement between annotators at the entity and scheme level. The mean Kappa value for the glaucoma and T2DM corpora was 0.74 and 0.68, respectively, for single entities. The micro-averaged F1 score to measure inter-annotator agreement for complex entities (i.e. slot-filling templates) was 0.81.The BERT-base baseline method for entity recognition achieved average micro- F1 scores of 0.76 for glaucoma and 0.77 for diabetes with exact matching.

Conclusions

In this work, we have created a corpus that goes beyond the existing clinical trial corpora, since it is annotated in a schematic way that represents the classes and properties defined in an ontology. Although the corpus is small, it has fine-grained annotations and could be used to fine-tune pre-trained machine learning models and transformers to the specific task of extracting information about clinical trial abstracts.For future work, we will use the corpus for training information extraction systems that extract single entities, and predict template slot-fillers (i.e., class data/object properties) to populate a knowledge base that relies on the C-TrO ontology for the description of clinical trials. The resulting corpus and the code to measure inter-annotation agreement and the baseline method are publicly available at https://zenodo.org/record/6365890.
On statistical convergence and strong Cesàro convergence by moduli for double sequences
Authors: León-Saavedra Fernando , Listán-García María del Carmen , Romero de la Rosa María del Pilar
Published: May 2022

A remarkable result on summability states that the statistical convergence and the strong Cesàro convergence are closely connected. Given a modulus functionf, we will establish that a double sequence that isf-strong Cesàro convergent is alwaysf-statistically convergent. The converse, in general, is false even for bounded sequences. However, we will characterize analytically the modulus functionsffor which the converse of this result remains true. The results of this paper adapt to several variables the results obtained in (León-Saavedra et al. in J. Inequal. Appl. 12:298, 2019).
Analysis of hemisphere-dependent effects of unilateral intrastriatal injection of α-synuclein pre-formed fibrils on mitochondrial protein levels, dynamics, and function
Authors: Creed Rose B. , Memon Adeel A. , Komaragiri Sindhu P. , Barodia Sandeep K. , Goldberg Matthew S.
Published: May 2022

Genetic and neuropathological evidence strongly implicates aberrant forms of α-synuclein in neurodegeneration. Antibodies specific for α-synuclein phosphorylated at serine 129 (pS129) are selective for the pathological protein aggregates that are characteristic of Parkinson’s disease (PD) and other synucleinopathies, such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although the etiology of most synucleinopathies remains uncertain, a large body of evidence points to mitochondrial dysfunction. The recent development of animal models based on intracranial injection of α-synuclein pre-formed fibrils (PFFs) has provided a valuable experimental system in which to study the spread and neurotoxicity of α-synuclein aggregates, yet the effects of PFF-induced protein aggregates on mitochondrial function and dynamics have not been rigorously examined in vivo. To help fill this knowledge gap, we injected the striatum of mice unilaterally with well-characterized small length (< 30 nm) PFFs or monomeric α-synuclein control and measured the distribution and extent of pS129 α-synuclein-immunoreactive aggregates, the loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, the abundance of mitochondrial proteins, and the activity of mitochondrial respiratory chain components at 3 months and 6 months post injection. Intrastriatal injection of small length PFFs, but not monomeric α-synuclein control, induced robust pS129 α-synuclein immunoreactive inclusions in the cortex, ventral midbrain, and striatum, as well as in rarely reported brain regions, such as the hippocampus, as early as 3 months post injection. Significant loss of nigral tyrosine hydroxylase-immunoreactive neurons was observed in the PFF-injected hemisphere at 3 months and 6 months post injection. The unilateral striatal injection of small length PFFs also caused hemisphere-dependent and treatment-dependent changes in the cortical levels of mitochondrial proteins such as VDAC1, COX-IV, and DRP-1, as well as functional changes in mitochondrial complex I activity in the contralateral striatum. Together, these data demonstrate that intrastriatal injection of mice with small length PFFs induces extensive bilateral protein aggregates, significant unilateral nigral cell loss, and altered contralateral levels of mitochondrial proteins and respiratory chain activity. Our data suggest this animal model may be useful for studying the role of mitochondrial dysfunction in α-synucleinopathies, for studying the hemisphere-dependent effects of α-synuclein aggregates, and for testing neuroprotective therapies that target mitochondrial dysfunction and protein aggregation.
Urban historic heritage buffer zone delineation: the case of Shedian
Authors: Lv Ruobing , Liu Yiping , Zhang Ling , Kong Dezheng
Published: May 2022

Buffer zones help protect historical heritage sites’ integrity, authenticity, and sustainability, and thus are an essential measure for protecting such sites. Traditional buffer zone delineation considers mainly the urban texture, a rigid boundary, visual corridor construction, and other factors. A more direct approach is designating a rated outer periphery that includes historic properties as a buffer zone. However, boundaries determined by single-value orientation tend to omit protected objects. A buffer zone formed by boundary translation and enclosure will include many low-value areas in the protection scope, thereby wasting resources and affecting historic towns’ natural development, resulting in a severe contradiction between humanity and the earth. This paper proposes a new method for delimiting buffer zones. The method arises from the field that covers the value assessment of cultural heritage and from the principles of comprehensive protection, which combine cultural heritage’s tangible and intangible properties. We used 29 historical preservation plans as samples to obtain statistics on their protection content, selected natural and agriculture landscapes, architectural features, construction quality, number of stories in a building, building age, protection class, street pattern, historical elements, urban texture, cultural industry, and cultural elements according to the frequency of occurrence as the primary factors affecting a buffer zone’s boundary demarcation. These factors were weighed and evaluated by the multi-criteria decision-making method (MCDM) to create a comprehensive evaluation map for helping determine a buffer zone’s boundary. Using such method, we identified the value of historical heritage through employing the quantitative analysis method of MCDM. We also used the evaluation result to determine the buffer zone boundary objectively. This approach rectifies the problems found in previous studies, namely an incomplete accounting of all relevant factors and a lack of data; it also provides a definition of an historical heritage buffer zone.
Array-size dependency of the upper limit wavelength normalized by array radius for the standard spatial autocorrelation method
Authors: Cho Ikuo
Published: May 2022

This study has shown for the analysis of the standard spatial autocorrelation (SPAC) method that the upper limit wavelength (ULW) normalized by the array radius (normalized ULW, NULW) strongly depends on the array size if we include small (radius r less than a few tens of meters) and very small (r about 1 m or less) microtremor arrays in addition to conventional larger arrays. First, field data of microtremor arrays were analyzed to demonstrate the possible use of small/very small arrays. Specifically, it was shown that, (i) even in the case of a very small array, random errors in the analysis results for very long wavelengths relative to the array radius are kept in an acceptable range for practical use; (ii) the signal-to-noise ratio (SNR) is a crucial factor determining the NULW; and (iii) an equation determining the NULW applies, namely the relation $$(\mathrm{NULW})\propto \sqrt{(\mathrm{SNR})}$$

(
NULW
)

∝

(
SNR
)

holds through very small to large arrays. The field data used are those distributed for blind prediction (BP) experiments for an international symposium (BP data), which consist of high-quality microtremor array data with various radii from very small (r = 0.58 m) to large (r = 555 m). It was then shown that SNRs of the BP data, and consequently the NULWs, increase with a decrease of array radius. Statistical data obtained from a few hundred arrays in our previous research also exhibit a similar tendency. The BP data lie around the maximum values of these distributions, showing the high quality of the BP data as well as supporting the array-size dependency of the NULW. Finally, the BP data were processed to identify the characteristics of the soil attenuation. It was found that the array-size dependency of NULW, as well as the large variations in NULW, can generally be explained by soil attenuation. It is plausible that the SNR of small/very small arrays are generally determined by the soil attenuation if the self-noise of the recording system is excluded. A logical conclusion drawn from these results, and also empirically supported, is that the practicality of very small arrays increases as the soil gets softer.

Graphical Abstract
Enhanced postoperative cancer therapy by iron-based hydrogels
Authors: Zhang Haomeng , Zhang Meng , Zhang Xinyu , Gao Yuan , Ma Yanling , Chen Hongyu , Wan Jipeng , Li Changzhong , Wang Fei , Sun Xiao
Published: May 2022

Surgical resection is a widely used method for the treatment of solid tumor cancers. However, the inhibition of tumor recurrence and metastasis are the main challenges of postoperative tumor therapy. Traditional intravenous or oral administration have poor chemotherapeutics bioavailability and undesirable systemic toxicity. Polymeric hydrogels with a three-dimensional network structure enable on-site delivery and controlled release of therapeutic drugs with reduced systemic toxicity and have been widely developed for postoperative adjuvant tumor therapy. Among them, because of the simple synthesis, good biocompatibility, biodegradability, injectability, and multifunctionality, iron-based hydrogels have received extensive attention. This review has summarized the general synthesis methods and construction principles of iron-based hydrogels, highlighted the latest progress of iron-based hydrogels in postoperative tumor therapy, including chemotherapy, photothermal therapy, photodynamic therapy, chemo-dynamic therapy, and magnetothermal-chemical combined therapy, etc. In addition, the challenges towards clinical application of iron-based hydrogels have also been discussed. This review is expected to show researchers broad perspectives of novel postoperative tumor therapy strategy and provide new ideas in the design and application of novel iron-based hydrogels to advance this sub field in cancer nanomedicine.
A novel prospect for an oviposition attraction of Chrysoperla carnea (Steph.) (Neuroptera: Chrysopidae) for its population upsurge
Authors: Sohail Mubasshir , Ali Shah Rukh , Muhammad Raza , Bukero Muhammad Aslam , Khalid Noman , Soomro Qadeer Ahmed
Published: May 2022

Background

Attraction and oviposition preference of the green lacewing,Chrysoperla carnea(Steph.)(Neuroptera: Chrysopidae), in response to prey availability in an ovipositional site was studied. The study aimed to investigate whether an adult attraction ofC. carneato oviposition on the substrate was affected by aphid juice (AJ) of fresh brassica aphid,Brevicoryne brassica.

Result

In laboratory bioassay, the number of eggs laid by female was significantly higher on AJ-treated area of substrate than control, indicating that oviposition was influenced by the AJ application. Attraction period of AJ lasted for 4 days. In Y-maze olfactometer studies, video tracking software ANY-maze® indicated thatC. carneaspent significant more time in the novel arm provided with AJ, showing an attraction. In the greenhouse study, AJ spray attracted a significantly higher number of male and female and considerably increased the number of eggs laid on brassica plant.

Conclusion

Fresh AJ may be a potential attractant for raising population of this predatory species at a particular location without being involved in rearing and augmentation process. This finding is of special interest and may be of benefit in biological control. As it is likely that the AJ spray could be used to enhanceC. carneapopulation attraction to the desire field.
Effect of low gamma irradiation doses on growth, productivity and chemical constituents of Jerusalem artichoke (Helianthus tuberosus) tubers
Authors: Mounir Amr M. , El-Hefny A. M. , Mahmoud S. H. , El-Tanahy A. M. M.
Published: May 2022

Background

This field experiment was carried out during the two successive seasons of 2019 and 2020 at the experimental farm of the National Center for Radiation Research and Technology, Nasr City, Cairo, Egypt, to evaluate the effect of low gamma irradiation doses (0, 2.5, 5 and10 Gray) on growth, yield and chemical constituents of Jerusalem artichoke tubers as one of the non-traditional vegetable crops which had a high nutritional and medicinal value.

Results

The obtained results show that gamma irradiation at dose rate 5 Gy gave the best results of plant height, number of branches, shoot fresh and dry weight compared with treatments exposed to gamma irradiation at dose rate 2.5 and 10 Gy and also higher photosynthetic pigments such as chlorophyll a, b, a + b and carotenoids than un-irradiated tubers. Same stimulative dose (5 Gy) yielded the highest total yield per feddan, plant yield, tuber fresh weight and dry matter percentage of tubers. Regarding chemical constituents of tubers, it was observed that gamma irradiation at dose 5 Gy scored higher percentage of nitrogen, phosphorus, potassium, total carbohydrates and inulin than other doses. From another point, the highest concentration of total soluble phenols and flavonoids was correlated with 5 and 10 Gy of gamma irradiation.

Conclusions

The moderate dose of gamma irradiation 5 Gy has a stimulative effect on growth of Jerusalem artichoke which reflects on tubers yield and their chemical constituents.
Medicinal plants used for treating cancer in Kenya: an ethnopharmacological overview
Authors: Omara Timothy , Odero Mark Peter , Obakiro Samuel Baker
Published: May 2022

Background

Cancer is one of the major causes of mortality worldwide. Though 30% of cancers can be treated when detected at early stages, their treatment has been compounded by resistance of tumor cells to anticancer drugs, side effects of the therapies, high treatment costs and limited access to medical services. In Africa, and particularly in the East African botanical plate, various ethnic groups cherish their traditions and embrace distinguished use of medicinal plants in the management of ailments like cancer. This study aimed at reviewing the ethnobotanical knowledge on the use of wild and cultivated plants as remedies for cancer treatment in Kenya as well as their phytochemical composition and reported anticancer activities.

Main body

Through extensive electronic review in PubMed, Science Direct, Scopus, Google Scholar, Web of Science, Scientific Electronic Library Online and the Google search engine, 145 plant species from 125 genera spread across 55 families were found to have been reported for cancer treatment in Kenya. The malignancies treated using the herbal remedies include squamous cell carcinoma of the gum, prostate, blood, bone, breast, colorectal, colon, oesophageal, lung, liver, skin, stomach, throat and uterine cancers. Most of the identified species have reported anticancer activities, withToddalia asiatica,Annona muricata,Carica papaya,Catharanthus roseus, Moringa oleifera,Ocimum gratissimum,Prunus africanaandZanthoxylum paracanthumbeing the most studied.

Conclusions

Despite the widespread use of medicinal plants in the management of cancer in Kenya, the bioactivity, safety aspects, responsible anticancer molecules and clinical studies are required to elucidate the mechanism of action of the compounds and confirm the potential of the unstudied species.
Diagnosis and management of 5-fluorouracil (5-FU)-induced acute leukoencephalopathy: lessons learnt from a single-Centre case series
Authors: Jose Neethu , Joel Anjana , Selvakumar Rajesh Joseph , Ramireddy Jebakarunya , John Ajoy Oommen , Georgy Josh Thomas , Singh Ashish , Ram Thomas Samuel
Published: May 2022

Background

The administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice.

Methods

We report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy.

Results

All (n = 5) had Naranjo scores of 6–7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2–4 days). All patients improved after conservative management with complete neurological recovery.

Conclusion

Prompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions.
Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Primary Breast Cancer
Authors: Bachelot Thomas , Cottu Paul , Chabaud Sylvie , Dalenc Florence , Allouache Djelila , Delaloge Suzette , Jacquin Jean-Philippe , Grenier Julien , Venat Bouvet Laurence , Jegannathen Apurna , Campone Mario , Del Piano Francesco , Debled Marc , Hardy-Bessard Anne-Claire , Giacchetti Sylvie , Mouret-Reynier Marie-Ange , Barthelemy Philippe , Kaluzinski Laure , Mailliez Audrey , Legouffe Eric , Sephton Matthew , Bliss Judith , Canon Jean-Luc , Penault-Llorca Frederique , Lemonnier Jerome , Cameron David , Andre Fabrice
Published: May 2022

PURPOSE

Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor–resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown.

PATIENTS AND METHODS

In this randomized double-blind phase III study, women with high-risk, hormone receptor–positive, human epidermal growth factor receptor 2–negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov (identifier: NCT01805271 ).

RESULTS

Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio, 0.95; 95% CI, 0.69 to 1.32; P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P < .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%.

CONCLUSION

Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting.
Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project
Authors: D'Agostino Mattia , Cairns David A. , Lahuerta Juan José , Wester Ruth , Bertsch Uta , Waage Anders , Zamagni Elena , Mateos María-Victoria , Dall'Olio Daniele , van de Donk Niels W.C.J. , Jackson Graham , Rocchi Serena , Salwender Hans , Bladé Creixenti Joan , van der Holt Bronno , Castellani Gastone , Bonello Francesca , Capra Andrea , Mai Elias K. , Dürig Jan , Gay Francesca , Zweegman Sonja , Cavo Michele , Kaiser Martin F. , Goldschmidt Hartmut , Hernández Rivas Jesús María , Larocca Alessandra , Cook Gordon , San-Miguel Jesús F. , Boccadoro Mario , Sonneveld Pieter
Published: May 2022

PURPOSE

Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+.

PATIENTS AND METHODS

The European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated.

RESULTS

In the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, t(4;14) 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value.

CONCLUSION

The R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables.
Sexual Orientation and Gender Identity Data Collection in Oncology Practice: Findings of an ASCO Survey
Authors: Kamen Charles S. , Pratt-Chapman Mandi L. , Meersman Stephen C. , Quinn Gwendolyn P. , Schabath Matthew B. , Maingi Shail , Merrill Janette K. , Garrett-Mayer Elizabeth , Kaltenbaugh Melinda , Schenkel Caroline , Chang Shine
Published: May 2022

PURPOSE:

Lack of collection of sexual orientation and gender identity (SOGI) data in oncology practices limits assessment of sexual and gender minority (SGM) cancer patients' experiences and restricts opportunities to improve health outcomes of SGM patients. Despite national calls for routine SOGI data collection, individual-level and institutional barriers hinder progress. This study aimed to identify these barriers in oncology.

METHODS:

An online survey of ASCO members and others assessed SOGI data collection in oncology practices, institutional characteristics related to SOGI data collection, respondents' attitudes about SOGI data and SGM patients, and respondent demographics. Logistic regression calculated adjusted odds ratios (ORs) and 95% CIs for factors associated with sexual orientation (SO) and gender identity (GI) data collection.

RESULTS:

Less than half of 257 respondents reported institutional SO and GI data collection (40% and 46%, respectively), whereas over a third reported no institutional data collection (34% and 32%, respectively) and the remainder were unsure (21% and 17%, respectively). Most respondents felt that knowing both SO and GI was important for quality care (77% and 85%, respectively). Collection of SO and GI was significantly associated in separate models with leadership support (ORs = 8.01 and 6.02, respectively), having resources for SOGI data collection (ORs = 10.6 and 18.7, respectively), and respondents' belief that knowing patient SO and GI is important (ORs = 4.28 and 2.76, respectively). Themes from qualitative comments mirrored the key factors identified in our quantitative analysis.

CONCLUSION:

Three self-reinforcing factors emerged as critical drivers for collecting SOGI data: leadership support, dedicated resources, and individual respondents' attitudes. Policy mandates, implementation science, and clinical reimbursement are strategies to advance meaningful data collection and use in clinical practice.
The Bloch oscillations of spin-orbit coupled Bose-Einstein condensates in deep optical lattices
Authors: Zhang Yan-Chao , Jiao Chen , Zhang Ai-Xia , Xue Ju-Kui
Published: May 2022

We study the ground state and the Bloch oscillations of the spin-orbit coupled Bose-Einstein condensates in one-dimensional deep optical lattices. The phase transition between the zero-momentum phase and the plane-wave phase in untilted deep optical lattices is studied analytically. The Bloch oscillations in tilted lattices started in different ground state phases are analyzed. It is found that the Bloch dynamics is harmonic (anharmonic) in the zero-momentum phase (plane-wave phase). Furthermore, the modification of the Bloch oscillations induced by spin-orbit coupling, tunnelling coefficient and the external force (the inclination of the tilt) is revealed. In addition, the analytical condition for emerging the long-lived Bloch oscillations is obtained and the corresponding diagram in parameter space is provided. Particularly, we find that the spin-orbit coupling can extend the duration of the Bloch oscillations in the plane-wave phase. We provide an effective method to manipulate the Bloch dynamics in the deep optical lattices.
Chaotic advection and particle pairs diffusion in a low-dimensional truncation of two-dimensional magnetohydrodynamics
Authors: Carbone Francesco , Telloni Daniele , Zank Gary , Sorriso-Valvo Luca
Published: May 2022

The chaotic advection of fluid particle pairs is investigated though a low-order model of two-dimensional magnetohydrodynamic (MHD), where only five nonlinearly interacting modes are retained. The model is inthrinsically inhomogeneous and anisotropic because of the influence of large-scale fluctuations. Therefore, even though dynamically chaotic, the fields are unable to form the typical scaling laws of fully developed turbulence. Results show that a super-ballistic dynamics, reminiscent of the Richardson law of particle-pairs diffusion in turbulent flows, is robustly obtained using the truncated model. Indeed, even in the strongly reduced truncation presented here, particle diffusion in MHD turbulence has the same laws as the separation of velocity of particle pairs. The inherent anisotropy only affects the scaling of diffusivity, by enhancing the diffusion properties along one direction for small time-scales. Finally, when further anisotropy is introduced in the system through Alfvén waves, fluid particles are trapped by these, and super-ballistic diffusion is replaced by Brownian-like diffusion. On the other hand, when the magnetic field is removed, the kinetic counterpart of the model does not show super-ballistic dynamics.
Combined Spinal-Epidural for Loop Ileostomy in a Patient With End-Stage Amyotrophic Lateral Sclerosis: A Case Report
Authors: Roth Anna F. , Harris Mark J.
Published: May 2022

Anesthesia can be a challenge for patients with amyotrophic lateral sclerosis (ALS). This progressive neurological disease is associated with a high risk of aspiration and postoperative ventilatory failure. Our patient was a 72-year-old man with ALS, quadriplegia, bulbar symptoms, dysphagia, and dysarthria who underwent palliative exploratory laparotomy and loop ileostomy creation. He received a single-shot spinal anesthetic at L4-L5 and a thoracic T11-12 epidural. He tolerated the procedure well with no perioperative pulmonary complications or worsening of his ALS. To reduce the risks of general anesthesia, we chose a neuraxial approach.
Intrinsic function of the peptidylarginine deiminase PADI4 is dispensable for normal haematopoiesis
Authors: Young Christine , Russell John R. , Van De Lagemaat Louie N. , Lawson Hannah , Mapperley Christopher , Kranc Kamil R. , Christophorou Maria A.
Published: May 2022

Peptidylarginine deiminases (PADIs) are strongly associated with the development of autoimmunity, neurodegeneration and cancer but their physiological roles are ill-defined. The nuclear deiminase PADI4 regulates pluripotency in the mammalian pre-implantation embryo but its function in tissue development is unknown. PADI4 is primarily expressed in the bone marrow, as part of a self-renewal-associated gene signature. It has been shown to regulate the proliferation of multipotent haematopoietic progenitors and proposed to impact on the differentiation of haematopoietic stem cells (HSCs), suggesting that it controls haematopoietic development or regeneration. Using conditional in vivo models of steady state and acute Padi4 ablation, we examined the role of PADI4 in the development and function of the haematopoietic system. We found that PADI4 loss does not significantly affect HSC self-renewal or differentiation potential upon injury or serial transplantation, nor does it lead to HSC exhaustion or premature ageing. Thus PADI4 is dispensable for cell-autonomous HSC maintenance, differentiation and haematopoietic regeneration. This work represents the first study of PADI4 in tissue development and indicates that pharmacological PADI4 inhibition may be tolerated without adverse effects.
Modelling the structure of Short Gastrulation and generation of a toolkit for studying its function in Drosophila
Authors: Frampton Sophie L. , Sutcliffe Catherine , Baldock Clair , Ashe Hilary L.
Published: May 2022

A BMP gradient is essential for patterning the dorsal-ventral axis of invertebrate and vertebrate embryos. The extracellular BMP binding protein Short Gastrulation (Sog) in Drosophila plays a key role in BMP gradient formation. In this study, we combine genome editing, structural and developmental approaches to study Sog function in Drosophila. We generate a sog knockout fly stock, which allows simple reintegration of altered versions of the sog coding sequence. As proof-of-principle, we test the requirement for two cysteine residues that were previously identified as targets for palmitoylation, which has been proposed to enhance Sog secretion. However, we show that the sogC27,28S mutant is viable with only very mild phenotypes, indicating that these residues and their potential modification are not critical for Sog secretion in vivo. Additionally, we use experimental negative stain EM imaging and hydrodynamic data to validate the AlphaFold structure prediction for Sog. The model suggests a more compact shape than the vertebrate ortholog Chordin and conformational flexibility between the C-terminal von Willebrand C domains. We discuss how this altered compactness may contribute to mechanistic differences in Sog and Chordin function during BMP gradient formation.

This article has an associated First Person interview with the first author of the paper.
Fetal brain MRI: Neurometrics, Typical Diagnoses, and Resolving Common Dilemmas
Authors: Brady Darragh , Schlatterer Sarah D , Whitehead Matthew T
Published: May 2022

This review presents a practical approach to imaging the fetal brain by MRI. Herein, we demonstrate how to measure brain structures and fluid spaces, and discuss the importance of comparing measurements to normative biometric references at a corresponding gestational age. We present some common imaging dilemmas of the technical aspects of fetal MRI with regards to typical regions of abnormality including the cerebrum, the ventricular system, and the posterior fossa, and discuss how to resolve them.
High-resolution neurosonographic examination of the lenticulostriate vessels in neonates with hypoxic-ischemic encephalopathy
Authors: Lyo Shawn , Tierradentro-Garcia Luis Octavio , Viaene Angela Nicole , Hwang Misun
Published: May 2022

Objective

To assess the feasibility of visualizing lenticulostriate vessels (LV) using a linear high-resolution ultrasound probe and characterize LV morphology to determine whether morphological alterations in LV are present in neonatal hypoxic–ischemic encephalopathy (HIE) as compared to the unaffected infants.

Methods

We characterized LV by their echogenicity, width, length, tortuosity, and numbers of visualized stems/branches in neurosonographic examinations of 80 neonates. Our population included 45 unaffected (non-HIE) and 35 with clinical and/or imaging diagnosis of HIE. Of the neonates with clinical diagnosis of HIE, 16 had positive MRI findings for HIE (HIE+MRI) and 19 had negative MRI findings (HIE-MRI). Annotations were performed twice with shuffled data sets at a 1-month interval and intrarater reliability was assessed. Focused comparison was conducted between non-HIE, HIE+MRI and HIE-MRI neonates whose images were acquired with a high frequency linear transducer.

Results

Studies acquired with the two most frequently utilized transducers significantly differed in number of branches (p = 0.002), vessel thickness (p = 0.007) and echogenicity (p = 0.009). Studies acquired with the two transducers also significantly differed in acquisition frequency (p < 0.001), thermal indices (p < 0.001) and use of harmonic imaging (p < 0.001). Groupwise comparison of vessels imaged with the most frequently utilized transducer found significantly fewer branches in HIE + MRI compared to HIE-MRI negative and non-HIE patients (p = 0.005).

Conclusion

LV can be visualized in the absence of pathology using modern high-resolution neurosonography. Visualization of LV branches varies between HIE + MRI, HIE-MRI neonates and controls.

Advances in knowledge

High-resolution neurosonography is a feasible technique to assess LV morphology in healthy neonates and neonates with HIE.
Guidance on medical physics expert support for nuclear medicine
Authors: Fraser Louise , Parkar Nasreen , Adamson Kathryn , Fletcher Alison , Julyan Peter , Kalirai Charnie , McGowan Daniel , McKiddie Fergus
Published: May 2022

The Ionising Radiation (Medical Exposure) Regulations require employers to appoint suitable medical physics experts (MPE) for nuclear medicine services, and they also define the areas where MPEs are required to provide advice and specify matters that they must contribute towards. Applications for employer licences under IR(ME)R require employers to specify the level of MPE support available and if this is provided by onsite MPEs or remotely. Assessment of these applications by the Administration of Radioactive Substances Advisory Committee (ARSAC) has highlighted variability in the levels of MPE support being provided for similar services across the UK. A working party including representatives from IPEM, ARSAC, BIR and BNMS was formed and has produced these recommendations on MPE support. Nuclear medicine services were divided into seven broad categories and MPE support for each category has been considered. However, some services that differ from the scenarios provided in this guidance may require different levels of MPE support. Positron emission tomography (PET)/CT and gamma camera imaging have been considered separately here, although it is recognised that both PET/CT and gamma cameras are often sited within the same department in many centres. The separation has been done for pragmatic purposes, as there are felt to be sufficient differences in the MPE role requirements. This guidance sets out recommendations for MPE support, and broader physics support, to run a safe nuclear medicine service and defines the responsibilities of these staff for a range of clinical nuclear medicine services. The recommendations on MPE support made are advice, but will assist employers in meeting regulatory requirements.
Radiation doses in the United Kingdom breast screening programmes 2016–2019
Authors: Loveland John , Young Kenneth C , Oduko Jennifer M , Mackenzie Alistair
Published: May 2022

Objectives:

To record the radiation doses involved in UK breast screening and to identify any changes since previous publications related to technical factors and the population screened.

Methods:

Mammographic exposure factors for 68,998 women imaged using 411 X-ray sets spread across the UK were compiled. Local output and half value layer measurements for each X-ray set were used to estimate mean glandular dose (MGD) using the standard UK method.

Results:

Mean MGDs in digital mammography have increased by 11% since 2010–12 for both medio-lateral oblique (MLO) and cranio-caudal (CC) views. The mean compressed breast thickness (CBT) has increased (4.8% CC, 5.2% MLO) over the same period. The mean MLO CBT value of 62.4 ± 0.1 mm is outside the 50 to 60 mm range used for diagnostic reference levels. The increase in MGD is consistent with the CBT changes. The mean MGD in the 50 to 60 mm CBT range is 1.44 ± 0.03 mGy for MLO views. CBT varies with age and peaks at 51.

Conclusions:

Mean CBT has increased with time, and this has increased mean MGDs for digital mammography. CBT also varies with age.

Advances in knowledge:

Updated average MGDs in the UK are provided. There is evidence that breast size is increasing in the UK and that mean CBT is affected by age-related changes in the breast.
Translevator perineal hernia; an incidental rare imaging presentation
Authors: Coalter Wendy S , Siddiqui Salman A
Published: May 2022

Translevator perineal hernias are rare pelvic floor defects that can be classified based on their anatomical location as either anterior or posterior relative to the transverse perineal muscle. This report describes an unusual clinical and radiological presentation of a posterior perineal hernia in an elderly lady. The case highlights the limitations of CT when findings are not definitive and the role of MRI as a superior problem-solving tool to better delineate the pelvic anatomy, exclude sinister pathology and confirm the diagnosis.