bluuebunny/crossref_metadata_2025 huggingface dataset:
T1 relaxation: Chemo-physical fundamentals of magnetic resonance imaging and clinical applications
Authors: Gaeta Michele , Galletta Karol , Cavallaro Marco , Mormina Enricomaria , Cannizzaro Maria Teresa , Lanzafame Ludovica Rosa Maria , D’Angelo Tommaso , Blandino Alfredo , Vinci Sergio Lucio , Granata Francesca
Published: August 2024

A knowledge of the complex phenomena that regulate T1 signal on Magnetic Resonance Imaging is essential in clinical practice for a more effective characterization of pathological processes. The authors review the physical basis of T1 Relaxation Time and the fundamental aspects of physics and chemistry that can influence this parameter. The main substances (water, fat, macromolecules, methemoglobin, melanin, Gadolinium, calcium) that influence T1 and the different MRI acquisition techniques that can be applied to enhance their presence in diagnostic images are then evaluated. An extensive case illustration of the different phenomena and techniques in the areas of CNS, abdomino-pelvic, and osteoarticular pathology is also proposed.

Critical relevance statement

T1 relaxation time is strongly influenced by numerous factors related to tissue characteristics and the presence in the context of the lesions of some specific substances. An examination of these phenomena with extensive MRI exemplification is reported.

Key Points

The purpose of the paper is to illustrate the chemical-physical basis of T1 Relaxation Time.

MRI methods in accordance with the various clinical indications are listed.

Several examples of clinical application in abdominopelvic and CNS pathology are reported.

Graphical Abstract
Deep learning-based pseudo-CT synthesis from zero echo time MR sequences of the pelvis
Authors: Getzmann Jonas M. , Deininger-Czermak Eva , Melissanidis Savvas , Ensle Falko , Kaushik Sandeep S. , Wiesinger Florian , Cozzini Cristina , Sconfienza Luca M. , Guggenberger Roman
Published: August 2024

Objectives

To generate pseudo-CT (pCT) images of the pelvis from zero echo time (ZTE) MR sequences and compare them to conventional CT.

Methods

Ninety-one patients were prospectively scanned with CT and MRI including ZTE sequences of the pelvis. Eleven ZTE image volumes were excluded due to implants and severe B1 field inhomogeneity. Out of the 80 data sets, 60 were used to train and update a deep learning (DL) model for pCT image synthesis from ZTE sequences while the remaining 20 cases were selected as an evaluation cohort. CT and pCT images were assessed qualitatively and quantitatively by two readers.

Results

Mean pCT ratings of qualitative parameters were good to perfect (2–3 on a 4-point scale). Overall intermodality agreement between CT and pCT was good (ICC = 0.88 (95% CI: 0.85–0.90); p < 0.001) with excellent interreader agreements for pCT (ICC = 0.91 (95% CI: 0.88–0.93); p < 0.001). Most geometrical measurements did not show any significant difference between CT and pCT measurements (p > 0.05) with the exception of transverse pelvic diameter measurements and lateral center-edge angle measurements (p = 0.001 and p = 0.002, respectively). Image quality and tissue differentiation in CT and pCT were similar without significant differences between CT and pCT CNRs (all p > 0.05).

Conclusions

Using a DL-based algorithm, it is possible to synthesize pCT images of the pelvis from ZTE sequences. The pCT images showed high bone depiction quality and accurate geometrical measurements compared to conventional CT.

Critical relevance statement

pCT images generated from MR sequences allow for high accuracy in evaluating bone without the need for radiation exposure. Radiological applications are broad and include assessment of inflammatory and degenerative bone disease or preoperative planning studies.

Key Points

pCT, based on DL-reconstructed ZTE MR images, may be comparable with true CT images.

Overall, the intermodality agreement between CT and pCT was good with excellent interreader agreements for pCT.

Geometrical measurements and tissue differentiation were similar in CT and pCT images.

Graphical Abstract
Characteristics of imaging in hepatic inflammatory pseudotumors: a comparison between IgG4-related and IgG4-unrelated cases
Authors: Lin Hua , Liu Ying , Wei Youyong , Guan Xiaohui , Yu Shuilian , Man Yuping , Deng Demao
Published: August 2024

Objectives

The objective of this study was to examine the imaging features of hepatic inflammatory pseudotumors (IPTs) associated with IgG4-related and IgG4-unrelated conditions and to enhance the approach toward distinguishing between these two types of IPTs.

Methods

A retrospective study was conducted, involving 20 patients diagnosed with hepatic IPTs. Imaging procedures were conducted within a timeframe of 4 weeks prior to hepatectomy or biopsy. The imaging features were then analyzed and compared using chi-squared analysis.

Results

Seventeen (81.0%) IPTs were located in the hepatic subcapsular area; six (66.7%) IgG4-related IPTs were distributed around the hepatic hilum; and eleven (91.7%) IgG4-unrelated and three (33.3%) IgG4-related IPTs had unclear boundaries. All lesions exhibited similar characteristics in CT scans, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI), with the apparent diffusion coefficient (ADC) values slightly higher than the surrounding liver tissue. Delayed hypoenhancement, observed in five cases (55.6%), was exclusively present in IgG4-related IPTs. The remaining IPT lesions displayed progressive enhancement, septal and marginal enhancement, and persistent enhancement. Central enhancement was absent in three IgG4-related IPTs (33.3%) and ten IgG4-unrelated IPTs (83.3%). The duct-penetrating sign was identified in two IgG4-unrelated IPTs (16.7%) and seven IgG4-related IPTs (77.8%). Furthermore, seven patients with IgG4-related IPTs had additional lesions outside the liver.

Conclusions

IgG4-related lesions are frequently found in the vicinity of the hepatic hilum; they display the duct-penetrating sign and affect other organs as well. Both groups exhibited progressive or persistent contrast enhancement in typical IPT lesions, but delayed hypoenhancement was only observed in the IgG4-related IPT group. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement.

Critical relevance statement

Differences in imaging features differentiate IgG4-related and -unrelated inflammatory pseudotumors (IPT). IgG4-related lesions are frequently near the hepatic hilum, display duct-penetrating sign, and affect other organs. Only the IgG4-related group demonstrated delayed hypoenhancement. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement.

Key Points

Compared with IgG 4-unrelated IPTs, IgG4-related IPTs show delayed hypoenhancement and affect other organs.

IgG4-unrelated IPTs have unclear boundaries and lack central enhancement.

Improved IPT diagnostic capabilities can help minimize additional, potentially unnecessary, interventions.

Graphical Abstract
Barriers and facilitators of access to maternity care for African-born women living in Australia: a meta-synthesis of qualitative evidence
Authors: Bali Ayele Geleto , Vasilevski Vidanka , Sweet Linda
Published: August 2024

Background

Adverse perinatal health outcomes are notably high among African-born women living in Australia. This problem is partly attributed to their lower engagement in maternity care services as compared to Australian-born women. Various barriers might limit African-born women’s access to and use of services; however, these barriers are not well documented. Therefore, this review aimed to synthesise current qualitative evidence on barriers and facilitators of access to maternity care for African-born women living in Australia.

Methods

The search was conducted in MEDLINE, CINAHL, Embase, PsychInfo, and Maternity and Infant Care databases on 16 April 2023. All articles retrieved were meticulously screened for eligibility by two independent reviewers with any disagreements resolved through discussion. The quality of the included articles was evaluated using the Mixed Methods Appraisal Tool. Studies were screened in Covidence and analysed in NVivo. The findings were organised and presented using Levesque’s framework of healthcare access.

Results

Out of 558 identified papers, 11 studies comprising a total of 472 participants met the eligibility criteria. The review highlighted provider-side barriers such as shortage of information, unmet cultural needs, long waiting times, low engagement of women in care, discrimination, and lack of continuity of care. User-side barriers identified include communication issues, difficulty navigating the health system, and lack of trustful relationships with healthcare providers. In contrast, the review pinpointed provider-side facilitators including positive staff attitudes, service availability, and the proximity of facilities to residential homes, while user-side facilitators such as cultural assimilation and feeling valued by healthcare providers were noted.

Conclusions

This review identified barriers and facilitators of access to maternity care for African-born women living in Australia. Empirical evidence that would inform potential changes to policy and practice to address African-born women’s unique health needs was highlighted. Designing and implementing a culturally safe service delivery model could remove the identified access barriers and improve African-born women’s engagement in maternity care. Moreover, reinforcing factors associated with positive healthcare experiences is essential for improving maternity care access for this priority population.

Systematic review registration

PROSPERO CRD42023405458.
Disparities in hepatitis B virus healthcare service access among marginalised poor populations: a mixed-method systematic review
Authors: Li Caixia , Thapa Dejina , Mi Qian , Gao Yuanxiu , Fu Xia
Published: August 2024

Background

Marginalised poor populations, characterised by poverty and social exclusion, suffer disproportionately from hepatitis B virus (HBV) infections and encounter substantial disparities in access to healthcare. This has further exacerbated the global HBV burden and precluded progress towards HBV elimination. This mixed-method systematic review aimed to synthesise their utilisation and influencing factors in HBV healthcare services, including screening, vaccination, treatment, and linkage-to-care.

Methods

Eleven databases were searched from their inception to May 4, 2023. Quantitative and qualitative studies examining the factors influencing HBV healthcare access among marginalised poor populations were included. A meta-analysis was conducted to synthesise the pooled rates of HBV healthcare utilisation. The factors influencing utilisation were integrated and visualised using a health disparity research framework.

Results

Twenty-one studies were included involving 13,171 marginalised poor individuals: sex workers, rural migrant workers, irregular immigrants, homeless adults, and underprivileged individuals. Their utilisation of HBV healthcare ranged from 1.5% to 27.5%. Meta-analysis showed that the pooled rate of at least one dose of the HBV vaccine barely reached 37% (95% confidence interval: 0.26‒0.49). Fifty-one influencing factors were identified, with sociocultural factors (n = 19) being the most frequently reported, followed by behavioural (n = 14) and healthcare system factors (n = 11). Socio-cultural barriers included immigration status, prison history, illegal work, and HBV discrimination. Behavioural domain factors, including previous testing for sexually transmitted diseases, residential drug treatment, and problem-solving coping, facilitated HBV healthcare access, whereas hostility coping exerted negative influences. Healthcare system facilitators comprised HBV health literacy, beliefs, and physician recommendations, whereas barriers included service inaccessibility and insurance inadequacies. The biological and physical/built environments were the least studied domains, highlighting that geographical mobility, shelter capacity, and access to humanitarian health centres affect HBV healthcare for marginalised poor populations.

Conclusions

Marginalised poor populations encounter substantial disparities in accessing HBV healthcare, highlighting the need for a synergistic management approach, including deploying health education initiatives to debunk HBV misperceptions, developing integrated HBV management systems for continuous tracking, conducting tailored community outreach programmes, and establishing a human rights-based policy framework to guarantee the unfettered access of marginalised poor populations to essential HBV services.
Spray-assisted drop formation liquid-phase microextraction for the determination of sertraline in environmental water samples with matrix-matching calibration in GC–MS
Authors: Zeytinci Nagehan Kübra , Akbıyık Hilal , Tezgin Emine , Zaman Buse Tuğba , Bozyiğit Gamze Dalgıç , Şaylan Meltem , Bakırdere Sezgin
Published: August 2024

Sertraline is used as an antidepressant drug for the treatment of psychiatric disorders, including anxiety and depression. In the current study, a simple and effective method was developed for the sensitive monitoring of sertraline in water samples using a GC–MS system. The spray-assisted droplet formation liquid-phase microextraction (SADF-LPME) method was used as a sample preparation method for the enrichment of analytes. Accordingly, dichloromethane was used as an extraction solvent and easily dispersed into a sample/standard solution using a lab-made modified spray device without using a dispersing solvent. The significant factors affecting the SADF-LPME efficiency, including sample pH, mixing conditions, extraction solvent type, and spray cycle, were univariately optimized to ascertain the extraction performance and applicability of the system. Under the optimized conditions, the plotted calibration curve of the method was linear in the range of 100.2–2011.7 µg/kg (mass-based standard preparation) with a good correlation coefficient (R2) of 0.9997. The detection and quantification limits of method were found to be 37.5 and 125 µg/kg, respectively. Validation of the method was successfully carried out using different tap water samples and applying a matrix-matching calibration strategy. The acceptable percent recoveries were recorded between 77.3 and 133.7%, with high repeatability. The recommended method is an alternative and fast extraction method with several advantages, including a simple experimental process, good dispersibility, and fast and superior extraction performance. It can be readily applicable to the monitoring and quantification of sertraline in tap water samples with good precision and accuracy.
Occult gastric carcinoma with microsatellite instability diagnosed 10 years after excision of metastatic lymph node: a case report
Authors: Tamamori Yutaka , Mori Takuya , Tanaka Akihiro , Okada Takuma , Tanaka Shogo , Fumimoto Yuichi , Yukimoto Kiyotaka , Sawada Ryugo , Sano Hisao , Ohta Yoshio , Taniguchi Hirokazu , Tsujinaka Toshimasa
Published: August 2024

Background

Suprapancreatic lymph node metastasis is one of the usual routes for gastric cancer. However, it is rare for the primary lesion to be found several years after resection of the suprapancreatic metastatic lymph node. This is a report of occult gastric carcinoma with microsatellite instability diagnosed 10 years after excision of a metastatic lymph node.

Case presentation

A 55-year-old female presented with suprapancreatic lymph node swelling during a medical examination. Gastroscopy revealed no malignancy. We performed an excisional biopsy via laparotomy and histologically suspected metastatic cancer of unknown origin. After nine and a half years, we detected early gastric cancer by gastroscopy and performed a distal gastrectomy. The gastric tumor was pathologically similar to the previous suprapancreatic tumor. Immunohistochemical examination revealed that both the stomach and suprapancreatic lymph node exhibited microsatellite instability, suggesting that the two lesions were of the same origin.

Conclusions

This case is considered valuable because there have been no previous reports of gastric cancer with characteristics of high microsatellite instability in which the primary tumor was identified a long time after resection of metastatic lesions.
Integration of patient and public involvement in a doctoral research study using the research cycle
Authors: Pearson Helen , Bell Carol , Cox Karl , Kayum Catherine , Knox Leona , Gibson Faith , Myall Michelle , Darlington Anne-Sophie , Potter Emma , Bird Nicholas
Published: August 2024

Background

Patient and public involvement (PPI) in research is widely acknowledged as essential to achieving successful and impactful research. Despite this acknowledgement, there are limited reports on how to approach and apply meaningful PPI throughout the research cycle and how to address challenges for researchers such as doctoral students, particularly when undertaking research on sensitive topics. This paper provides insights and examples for researchers new to PPI, on the impact of active PPI and recommendations for building and developing a PPI group in a paediatric focused doctoral research study with bereaved parents and carers.

Methods

PPI was informed by the research cycle. The GRIPP2 short-form checklist was used to report PPI. The research was funded by the National Institute for Health and Care Research.

Results

PPI enhanced the research through input into the study design, recruitment, co-design of the study website and branding; and ethics amendments to increase participation in response to the COVID-19 pandemic. The literature review was extended to incorporate a PPI consultation phase and members contributed to data analysis. A flexible approach enabled involvement to develop iteratively throughout the research study, resulting in changes being made to enhance the study design and outcomes.

Conclusion

This paper contributes to the limited knowledge base on embedding PPI into a doctoral research study and within the paediatric setting specifically working in partnership with bereaved parents and carers. Employing an adaptive approach to meet individual PPI needs, building a trusting and respectful partnership, creating shared ownership and investment in the research, are essential components to successful PPI.
Muscle ultrastructure and histopathological findings in a Brazilian single-centre series of genetically classified telethoninopathy patients
Authors: Cotta Ana , Carvalho Elmano , da-Cunha-Júnior Antonio Lopes , da Silveira Eni Braga , Cordeiro Bruno Arrivabene , Lima Maria Isabel , Navarro Monica Machado , Godinho Frederico , Valicek Jaquelin , Menezes Miriam Melo , Nunes-Neves Simone Vilela , Vargas Antonio Pedro , da-Silva-Neto Rafael Xavier , Costa-e-Silva Cynthia , Takata Reinaldo Issao , Cauhi Alexandre Faleiros , Paim Julia Filardi , Vainzof Mariz
Published: August 2024

Background

Telethoninopathy or TCAP-gene related Limb Girdle Muscular Dystrophy is a rare genetic disease that was first described in Brazil. There are around 100 families reported worldwide. Due to its rarity, detailed information on muscle biopsy light and electron microscopic features are lacking.

Cases presentation

Retrospective study of consecutive muscle biopsies performed in patients from a Neuromuscular Outpatient Clinic between 2011 and 2023. Inclusion criteria: telethoninopathy diagnosed by both immunohistochemistry and molecular studies. Seven patients (0.7% or 7/953) were found: five male and two female, admitted from 6 to 54 years old. Detailed light and electron microscopy findings are illustrated. Muscle imaging is presented. A dystrophic pattern on muscle biopsy was found in 57% (4/7) of the patients. Other 43% (3/7) presented myopathic features such as variation in fibre calibre, nuclear internalization, rimmed vacuoles, and oxidative irregularities. Morphometry disclosed type 1 lobulated fibres that were 34%, 52%, and 57% smaller than type 2 fibres, respectively, in three patients, without type 1 fibre predominance. Electron microscopy demonstrated nuclear pseudoinclusions, pyknosis, multifocal loss of the sarcolemma, and 17 nm intrasarcoplasmic filamentous inclusions. All patients presented: (1) complete absence of the immunohistochemical expression of telethonin, and (2) the homozygous c.157C > T, p.(Gln53*) pathogenic variant in exon 2 of the TCAP gene.

Conclusion

Anti-telethonin immunohistochemistry may be helpful in unsolved cases with nonspecific myopathic abnormalities, specially with small type 1 lobulated fibres. Appropriate diagnosis is important for adequate genetic counselling.
16S amplicon-based microbiome biomapping of a commercial broiler hatchery
Authors: Rothrock Michael J. , Zwirzitz Benjamin , Al Hakeem Walid G. , Oladeinde Adelumola , Guard Jean Y. , Li Xiang
Published: August 2024

Hatcheries, where eggs from multiple breeder farms are incubated and hatched before being sent to different broiler farms, represent a nexus point in the commercial production of broilers in the United States. Considering all downstream microbial quality and safety aspects of broiler production (live production, processing, consumer use) can be potentially affected by the hatchery, a better understanding of microbial ecology within commercial hatcheries is essential. Therefore, a commercial broiler hatchery was biomapped using 16S rRNA amplicon-based microbiome analyses of four sample type categories (Air, Egg, Water, Facility) across five different places in the pre-hatch, hatch, and post-hatch areas. While distinct microbiota were found for each sample type category and hatchery area, microbial community analyses revealed that Egg microbiota trended towards clustering with the facility-related samples when moving from the prehatch to post-hatch areas, highlighting the potential effect of the hatchery environment in shaping the pre-harvest broiler-related microbiota. Prevalence analyses revealed 20 ASVs (Core20) present in the core microbiota of all sample types and areas, with each ASV possessing a unique distribution throughout the hatchery. Interestingly, three Enterobacteriaceae ASVs were in the Core20, including Salmonella. Subsequent analyses showed that Salmonella, while a minor prehatch and hatch Core20ASV, dominated the Enterobacteriaceae niche and total microbiota in the chick pad feces in the post-hatch area of the hatchery, and the presence of this Salmonella ASV in the post-hatch feces was associated with swabs of breakroom tables. These findings highlight the complexity of commercial hatchery microbiota, including identifying chick pad feces and breakroom tables as potentially important sampling or disinfection targets for hatchery managers to focus their Salmonella mitigation efforts to reduce loads entering live production farms.
Association of VEGFR1, VEGFR2 and VEGFR3 polymorphisms with esophageal cancer risk: a case–control study
Authors: Walia Sukhpreet Kaur , Sambyal Vasudha , Sudan Meena , Uppal Manjit Singh , Guleria Kamlesh
Published: August 2024

Background

Esophageal cancer is the eleventh most common cancer and is the seventh leading cause of mortality worldwide. Vascular endothelial growth factor (VEGF) and its receptors pathway are a key regulator of angiogenesis and play an important role in carcinogenesis. The aim of current study was to evaluate the association of five VEGFR polymorphisms with esophageal cancer risk in patients from Punjab, North-west India.

Methods

This case–control study included 310 esophageal cancer patients and 325 age and gender matched healthy controls. VEGFR1-710C/T, VEGFR2-604 T/C (rs2071559), VEGFR2 1192 G/A (rs2305948), VEGFR2 1719A/T (rs1870377) and VEGFR3 (rs72816988) polymorphisms were genotyped by using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Restriction digestion products were analyzed on 2.4% agarose gel and genotype was assigned to each sample on the basis of fragments obtained after digestion. Randomly 10% samples were repeated by Sanger sequencing to revalidate the results.

Results

There was a significant association of CT genotype (OR = 0.28; 95%CI, 0.10–0.76; p = 0.01) and T allele (OR = 0.28; 95%CI, 0.10–0.77; p = 0.01) of VEGFR1-710C/T polymorphism with decreased risk of esophageal cancer. TC genotype of VEGFR2-604 T/C (OR = 0.66; 95%CI, 0.44–0.97; p = 0.03) and GA genotype of VEGFR2 1192G/A (OR = 0.54; 95%CI, 0.31–0.95; p = 0.03) polymorphisms were significantly associated with decreased risk of esophageal cancer. There was no significant difference in allele and genotype frequency of VEGFR2 1719A/T and VEGFR3 (rs72816988) polymorphisms between esophageal cancer patients and controls (p > 0.05). Haplotype analysis revealed that haplotype C-604A1719A1192 was significantly associated with the decreased esophageal cancer risk (OR = 0.44; 95%CI, 0.23–0.84; p = 0.01).

Conclusion

VEGFR1-710C/T, VEGFR2-604 T/C and VEGFR2 1192G/A polymorphisms were associated with the decreased risk of esophageal cancer in patients from Punjab, North-west India.

Graphical abstract
Diffuse pulmonary hemorrhage as a rare presentation of pheochromocytoma: a case report with review of the literature
Authors: Rasool Abid , Ganie Mohd Ashraf , Modi Sagar , Kandasamy Devasenathipathy , Bal C. S. , Agarwal Shipra , Sahar Tajali
Published: August 2024

A 37-year-old male patient with a past history of fluctuating hypertension and insulin-treated diabetes mellitus presented to our clinic with a 1-year history of sudden-onset cough, dyspnea, and frank hemoptysis. Examination showed asthenia, moderate anemia, uncontrolled blood pressure, and a past history of one admission for management of hemoptysis and cardiac failure. The evaluation showed mild anemia, azotemia, low ejection fraction, contrast-enhanced computed tomography (CECT) of the chest, and sputum suggestive of pulmonary hemorrhage. Investigation during current admission revealed proteinuria, left suprarenal mass on USG, and clear lung parenchyma on chest X-ray and CECT. Autoimmune workup for vasculitis was negative and 24-h urinary catecholamine levels were elevated with CECT abdomen confirming pheochromocytoma. His blood pressure was controlled and he underwent laparoscopic left adrenalectomy with confirmation on histopathology. Postoperatively he is doing well with minimal requirement of antihypertensive, and diabetes is controlled with diet and exercise only. This case highlights diffuse alveolar hemorrhage as a rare presentation of pheochromocytoma. This case also highlights that secondary cause of hypertension should always be ruled out in case of uncontrolled hypertension in young patients to prevent devastating complications.
Correlation between language and cognitive skills in Egyptian children with reading problems
Authors: El-Wahed Eman Ezzat Abd , Ragab Ahmed , Osman Dalia Mostafa , El-Shourbagy Hanan Anwar , El-Domiaty Eman Fathi , Rashad Asmaa El-Dessouky
Published: August 2024

Background

Reading problems are the most prevalent type of specific learning disability. Reading problems usually result from phonological deficits; however, it is unclear how much other linguistic abilities are impacted as well.

Objective

To study different language parameters and cognitive skills in a group of Egyptian children with reading problems to better understand the difficulties that need to be considered in rehabilitation programs for those children.

Methods

A case–control study was conducted on 30 children with reading problems having IQs above 85 and 30 normal control children matched for age and gender (their ages ranged from 7 to 9 years and 11 months). They underwent testing for dyslexia by the Arabic dyslexia assessment test, language evaluation using the Receptive Expressive Arabic Language Scale (REAL scale), and the Stanford-Binet intelligence scale, fifth edition.

Results

There were highly significant correlations between the severity of dyslexia and total language scores, most of REAL scale subtests. Also, highly significant correlations were detected between the severity of dyslexia and the total IQ, verbal IQ, and verbal working memory subtests. The linear regression model revealed a highly significant association between dyslexia and expressive language scaled scores, total language scaled scores, and a significant association with expressive vocabulary and understanding oral instructions subtests of REAL scale. Additionally, a highly significant association has been detected between dyslexia and the verbal working memory subtest of the Stanford-Binet test. Correlations between total language scores and intellectual abilities (total IQ, verbal IQ, and non-verbal IQ) revealed highly significant positive results.

Conclusion

Deficits in both receptive and expressive language were observed in children with reading problems. Expressive vocabulary, listening comprehension, and verbal working memory subtests are the most affected language and cognitive skills.
Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia
Authors: Chang Ti-Cheng , Chen Wenan , Qu Chunxu , Cheng Zhongshan , Hedges Dale , Elsayed Abdelrahman , Pounds Stanley B. , Shago Mary , Rabin Karen R. , Raetz Elizabeth A. , Devidas Meenakshi , Cheng Cheng , Angiolillo Anne , Baviskar Pradyuamna , Borowitz Michael , Burke Michael J. , Carroll Andrew , Carroll William L. , Chen I-Ming , Harvey Richard , Heerema Nyla , Iacobucci Ilaria , Wang Jeremy R. , Jeha Sima , Larsen Eric , Mattano Leonard , Maloney Kelly , Pui Ching-Hon , Ramirez Nilsa C. , Salzer Wanda , Willman Cheryl , Winick Naomi , Wood Brent , Hunger Stephen P. , Wu Gang , Mullighan Charles G. , Loh Mignon L.
Published: August 2024

PURPOSE

Although cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, ALL remains a leading cause of cancer death in children. Half of relapses arise in children initially classified with standard-risk (SR) disease.

MATERIALS AND METHODS

To identify genomic determinants of relapse in children with SR ALL, we performed genome and transcriptome sequencing of diagnostic and remission samples of children with SR (n = 1,381) or high-risk B-ALL with favorable cytogenetic features (n = 115) enrolled on Children's Oncology Group trials. We used a case-control study design analyzing 439 patients who relapsed and 1,057 who remained in complete remission for at least 5 years.

RESULTS

Genomic subtype was associated with relapse, which occurred in approximately 50% of cases of
PAX5
-altered ALL (odds ratio [OR], 3.31 [95% CI, 2.17 to 5.03];
P =
3.18 × 10
–8
). Within high-hyperdiploid ALL, gain of chromosome 10 with disomy of chromosome 7 was associated with favorable outcome (OR, 0.27 [95% CI, 0.17 to 0.42];
P
= 8.02 × 10
–10
; St Jude Children's Research Hospital validation cohort: OR, 0.22 [95% CI, 0.05 to 0.80];
P
= .009), and disomy of chromosomes 10 and 17 with gain of chromosome 6 was associated with relapse (OR, 7.16 [95% CI, 2.63 to 21.51];
P
= 2.19 × 10
–5
; validation cohort: OR, 21.32 [95% CI, 3.62 to 119.30];
P
= .0004). Genomic alterations were associated with relapse in a subtype-dependent manner, including alterations of
INO80
in
ETV6::RUNX1
ALL,
IKZF1
, and
CREBBP
in high-hyperdiploid ALL and
FHIT
in
BCR::ABL1
-like ALL. Genomic alterations were also associated with the presence of minimal residual disease, including
NRAS
and
CREBBP
in high-hyperdiploid ALL.

CONCLUSION

Genetic subtype, patterns of aneuploidy, and secondary genomic alterations determine risk of relapse in childhood ALL. Comprehensive genomic analysis is required for optimal risk stratification.
Menin Inhibition With Revumenib for
KMT2A
-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)
Authors: Issa Ghayas C. , Aldoss Ibrahim , Thirman Michael J. , DiPersio John , Arellano Martha , Blachly James S. , Mannis Gabriel N. , Perl Alexander , Dickens David S. , McMahon Christine M. , Traer Elie , Zwaan C. Michel , Grove Carolyn S. , Stone Richard , Shami Paul J. , Mantzaris Ioannis , Greenwood Matthew , Shukla Neerav , Cuglievan Branko , Kovacsovics Tibor , Gu Yu , Bagley Rebecca G. , Madigan Kate , Chudnovsky Yakov , Nguyen Huy Van , McNeer Nicole , Stein Eytan M. , Wei Andrew , Fleming Shaun , Sabins Himalee , Aldoss Ibrahim , Kovacsovics Tibor , Stone Richard , Arellano Martha , Patel Manish , Talati Chetasi , Chen Jing , Nachmias Boaz , Heiblig Mael , Fernandez Pau Montesios , Arnan-Sangerman Montserrat , Stein Eytan M. , Mantzaris Ioannis , Blachly James S. , Traer Elie , Zwaan C. Michael , Wolach Ofir , Marconi Giovanni , Bajel Ashish , Grove Carolyn S. , Mannis Gabriel N. , Schuh Andre , Thirman Michael , Byrd John , McMahon Christine M. , Dickens David S. , Perl Alexander , Greenwood Matthew , Issa Ghayas C. , Whitlock James , Shami Paul J. , DiPersio John
Published: August 2024

PURPOSE

Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with
KMT2A
-rearranged (
KMT2Ar
) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R)
KMT2Ar
acute leukemia.

METHODS

AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier:
NCT04065399
). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R
KMT2Ar
acute leukemia or with AML and nucleophosmin 1 (
NPM1
) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m
2
if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all
KMT2Ar
treated patients; efficacy was assessed in those with centrally confirmed
KMT2Ar
. The separate
NPM1
cohort of the trial is ongoing.

RESULTS

From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% (
P
= .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease.

CONCLUSION

Revumenib led to high remission rates with a predictable safety profile in R/R
KMT2Ar
acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.
Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer
Authors: Konda Bhavana , Sherman Eric J , Massarelli Erminia , Nieva Jorge , Muzaffar Jameel , Morris John C , Ryder Mabel , Ho Alan L , Agulnik Mark , Wei Lai , Handley Demond , Moses Catherine , Jacob Rajani , Wright John , Streicher Howard , Carson William , Shah Manisha H
Published: August 2024

Background

This investigator-initiated phase II trial aimed to evaluate the efficacy of cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) in previously treated patients with radioactive iodine-refractory differentiated thyroid cancer.

Methods

Eligible patients with radioactive iodine-refractory differentiated thyroid cancer who progressed on 1 prior line of vascular endothelial growth factor receptor-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length = 6 weeks), followed by cabozantinib plus nivolumab (cycle length = 4 weeks) until disease progression. The primary endpoint was objective response rate (ORR) within the first 6 months of treatment. A Simon optimal 2-stage design allowed for an interim analysis after accrual of 10 evaluable patients. At least 5 responses were needed to proceed to stage 2.

Results

Among 11 patients enrolled, the median age was 69 years. Prior vascular endothelial growth factor receptor-targeted therapies included lenvatinib, pazopanib, and sorafenib plus everolimus. Median follow-up was 7.9 months. Among 10 evaluable patients, ORR within the first 6 months of treatment was 10% (1 partial response). Median progression-free survival was 9 months (95% CI, 3.0–not reached) and median overall survival was 19.2 months (95% CI, 4.6–not reached). Grade 3/4 treatment-related adverse events (AEs) were noted in 55% (6/11) and grade 5 AEs in 18% (2/11) of patients. The most common treatment-related AE was hypertension. The study did not reach its prespecified efficacy threshold.

Conclusion

CaboNivoIpi had low ORRs and a high rate of grade ≥3 treatment-related AEs.

Clinical Trial Registration

NCT03914300
Political Partisanship, Confucian Collectivism, and Public Attitudes toward the Vaccination Policy in Taiwan
Authors: Yeh Ming-Jui , Hsieh Yu-Chun
Published: August 2024

Context: Conventional wisdom suggests that people with a collectivist tradition tend to comply more with the government's regulatory and even coercive disease-prevention policies. In addition to this sociocultural element, political partisanship is also an important aspect relating to people's willingness to cooperate with the government. This study aims to examine the relationships between these two factors and three dimensions of vaccination policy attitudes: common responsibility to take the vaccine, the government's vaccine mandate, and indignation over anti-vaxxers.

Methods: Using data from a nationally representative cross-sectional survey conducted in 2022 in Taiwan, this study applies multiple linear ordinary least squares regression to examine the relationships between vaccination policy attitudes and Confucian collectivism and political partisanship.

Findings: Confucian collectivism and political partisanship aligning with the ruling party are associated with attitudes supporting vaccination policy. For those who do not align with the ruling party, negative attitudes toward the vaccination policy appear in different dimensions according to the party they lean toward.

Conclusions: Confucian collectivism is prevalent in Taiwan and is related to public attitudes toward vaccination policy. This association is independent of political partisanship. Public health authorities should consider the sociocultural context and political atmosphere for the effectiveness of disease-prevention measures.
Developing long bones respond to surrounding tissues by trans-pairing of periosteal osteoclasts and endocortical osteoblasts
Authors: Kuroda Yukiko , Yoda Masaki , Kawaai Katsuhiro , Tatenuma Motoharu , Mizoguchi Toshihide , Ito Shinichirou , Kasahara Masataka , Wu Yanlin , Takano Hidekazu , Momose Atsushi , Matsuo Koichi
Published: August 2024

Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone-forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones. Analysis of endo-t-p activity in the cortex of mouse fibulae revealed osteoclasts under the periosteum compressed by muscles, and expression of RANKL in periosteal cells of the cambium layer. Furthermore, mature osteoblasts were localized on the endosteum, while preosteoblasts were at the periosteum and within cortical canals. X-ray tomographic microscopy revealed the presence of cortical canals more closely associated with endo- than with peri-t-p. Sciatic nerve transection followed by muscle atrophy and unloading induced circumferential endo-t-p with concomitant spread of cortical canals. Such canals likely supply the endosteum with preosteoblasts from the periosteum under endo-t-p, allowing bone shape to change in response to mechanical stress or nerve injury.
Cardiac arrhythmias in fish induced by natural and anthropogenic changes in environmental conditions
Authors: Vornanen Matti , Badr Ahmed , Haverinen Jaakko
Published: August 2024

A regular heartbeat is essential for maintaining the homeostasis of the vertebrate body. However, environmental pollutants, oxygen deficiency and extreme temperatures can impair heart function in fish. In this Review, we provide an integrative view of the molecular origins of cardiac arrhythmias and their functional consequences, from the level of ion channels to cardiac electrical activity in living fish. First, we describe the current knowledge of the cardiac excitation–contraction coupling of fish, as the electrical activity of the heart and intracellular Ca2+ regulation act as a platform for cardiac arrhythmias. Then, we compile findings on cardiac arrhythmias in fish. Although fish can experience several types of cardiac arrhythmia under stressful conditions, the most typical arrhythmia in fish – both under heat stress and in the presence of toxic substances – is atrioventricular block, which is the inability of the action potential to progress from the atrium to the ventricle. Early and delayed afterdepolarizations are less common in fish hearts than in the hearts of endotherms, perhaps owing to the excitation–contraction coupling properties of the fish heart. In fish hearts, Ca2+-induced Ca2+ release from the sarcoplasmic reticulum plays a smaller role than Ca2+ influx through the sarcolemma. Environmental changes and ion channel toxins can induce arrhythmias in fish and weaken their tolerance to environmental stresses. Although different from endotherm hearts in many respects, fish hearts can serve as a translational model for studying human cardiac arrhythmias, especially for human neonates.
Viewpoint-independent face recognition via extrapolation in paper wasps
Authors: Tibbetts Elizabeth A. , Weise Chloe , Pardo-Sanchez Juanita , Vi An Na
Published: August 2024

Visual recognition of three-dimensional signals, such as faces, is challenging because the signals appear different from different viewpoints. A flexible but cognitively challenging solution is viewpoint-independent recognition, where receivers identify signals from novel viewing angles. Here, we used same/different concept learning to test viewpoint-independent face recognition in Polistes fuscatus, a wasp that uses facial patterns to individually identify conspecifics. We found that wasps use extrapolation to identify novel views of conspecific faces. For example, wasps identify a pair of pictures of the same wasp as the ‘same’, even if the pictures are taken from different views (e.g. one face 0 deg rotation, one face 60 deg rotation). This result is notable because it provides the first evidence of view-invariant recognition via extrapolation in an invertebrate. The results suggest that viewpoint-independent recognition via extrapolation may be a widespread strategy to facilitate individual face recognition.
Nanoscale ultrastructures increase the visual conspicuousness of signalling traits in obligate cleaner shrimps
Authors: Caves Eleanor M. , Davis Alexander L. , Johnsen Sönke
Published: August 2024

Signal theory predicts organisms should evolve signals that are conspicuous to intended receivers in natural signalling environments. Cleaner shrimps remove ectoparasites from reef fish clients and many signal their intent to clean by whipping long, white antennae. As white is a reliably conspicuous colour in aquatic environments, we hypothesized that selection has acted to increase broad-spectrum antennal reflectance in cleaners. Using scanning electron microscopy, optical models and reflectance measurements, we found that the antennae in three obligate cleaner species from two families (Palaemonidae and Lysmatidae) had thick (∼6 µm) chitinous layers or densely packed high refractive index spheres (300–400 nm diameter), which models show increase reflectance (400–700 nm). Two facultative and non-cleaning species had no visible antennae ultrastructure beyond the chitinous exoskeleton. Antennae reflectance was significantly higher in obligate cleaners than in facultative and non-cleaning species. Our results suggest that some obligate cleaners may have evolved ultrastructures that increase the conspicuousness of their antennae as signals.
A Comparison of Pain Before and After Transfusion in Adult transfusion-dependent thalassemia (TDT) Using BPI-SF
Authors: Gamayani Uni , Dianathasari Santoso Shenny , Nugraha Hermawan Asep , Irani Fianza Pandji , Panigoro Ramdan
Published: August 2024

Background Pain is a complication in patients with transfusion-dependent thalassemia (TDT). There are several mechanisms underlying pain in people with thalassemia and low hemoglobin at the end of the transfusion cycle was the most etiology. Pain can develop into chronic pain and interfere with the quality of life. The Brief Pain Inventory Short Form (BPI-SF) can help identify pain in people with TDT. The present study aimed to compare pain before and after transfusion in adult TDT patients. Methods It was an analytical observational study using a cross-sectional design on adult TDT patients with pain who came to the Haemato-Oncology Clinic of Dr. Hasan Sadikin Hospital Bandung. This study was conducted from December 2020 to July 2021. All subjects were assisted in filling out the Indonesian version of the BPI-SF questionnaire hemoglobin levels were examined and before and after transfusion, then paired test analysis was performed using the Wilcoxon Test. Results This study is conducted on 60 adult TDT patients with symptoms of pain. The median value of pain intensity and pain interferes with life obtained from the Indonesian version of the BPI-SF score after transfusion decreased significantly compared to before transfusion (NRS 5 vs. 0 and 2.8 vs. 0; p=0.0001). Conclusion There is a significant difference in pain intensity and pain interfere with life in adults with TDT before and after transfusion. It is necessary to carry out pain assessments for thalassemia patients.
DAS Signal Modelling to Assist in Uptake of Active Travel
Authors: Ford Jason
Published: August 2024

Modelling distributed acoustic sensor signals will help local authorities plan active travel schemes anticipated to improve health and drive down emissions
UK-Launched Rocket Reaches Space But Fails to Deploy Satellites
Authors: Wade Andrew , Ford Jason
Published: August 2024

Team pledges to rectify technical failure that stymied landmark flight
A Fixed Position on Auxiliary Nuclear Power
Authors: Ford Jason
Published: August 2024

A lightweight, high-temperature nuclear reactor was pivotal to satellite navigation systems