bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardisation of conventional and advanced iterative reconstruction methods for Gallium-68 multi-centre PET-CT trials
Authors: Krokos Georgios , Pike Lucy C. , Cook Gary J. R. , Marsden Paul K.
Published: July 2021

Purpose

To assess the applicability of the Fluorine-18 performance specifications defined by EANM Research Ltd (EARL), in Gallium-68 multi-centre PET-CT trials using conventional (ordered subset expectation maximisation, OSEM) and advanced iterative reconstructions which include the systems’ point spread function (PSF) and a Bayesian penalised likelihood algorithm (BPL) commercially known as Q.CLEAR. The possibility of standardising the two advanced reconstruction methods was examined.

Methods

The NEMA image quality phantom was filled with Gallium-68 and scanned on a GE PET-CT system. PSF and BPL with varying post-reconstruction Gaussian filter width (2–6.4 mm) and penalisation factor (200–1200), respectively, were applied. The average peak-to-valley ratio from six profiles across each sphere was estimated to inspect any edge artefacts. Image noise was assessed using background variability and image roughness. Six GE and Siemens PET-CT scanners provided Gallium-68 images of the NEMA phantom using both conventional and advanced reconstructions from which the maximum, mean and peak recoveries were drawn. Fourteen patients underwent 68Ga-PSMA PET-CT imaging. BPL (200-1200) reconstructions of the data were compared against PSF smoothed with a 6.4-mm Gaussian filter.

Results

A Gaussian filter width of approximately 6 mm for PSF and a penalisation factor of 800 for BPL were needed to suppress the edge artefacts. In addition, those reconstructions provided the closest agreement between the two advanced iterative reconstructions and low noise levels with the background variability and the image roughness being lower than 7.5% and 11.5%, respectively. The recoveries for all methods generally performed at the lower limits of the EARL specifications, especially for the 13- and 10-mm spheres for which up to 27% (conventional) and 41% (advanced reconstructions) lower limits are suggested. The lesion standardised uptake values from the clinical data were significantly different between BPL and PSF smoothed with a Gaussian filter of 6.4 mm wide for all penalisation factors except for 800 and 1000.

Conclusion

It is possible to standardise the advanced reconstruction methods with the reconstruction parameters being also sufficient for minimising the edge artefacts and noise in the images. For both conventional and advanced reconstructions, Gallium-68 specific recovery coefficient limits were required, especially for the smallest phantom spheres.
Right-sided Bochdalek hernia in an adult with hepatic malformation and intestinal malrotation
Authors: Enomoto Naoki , Yamada Kazuhiko , Kato Daiki , Yagi Shusuke , Wake Hitomi , Nohara Kyoko , Takemura Nobuyuki , Kiyomatsu Tomomichi , Kokudo Norihiro
Published: July 2021

Background

Bochdalek hernia is a common congenital diaphragmatic defect that usually manifests with cardiopulmonary insufficiency in neonates. It is very rare in adults, and symptomatic cases are mostly left-sided. Diaphragmatic defects generally warrant immediate surgical intervention to reduce the risk of incarceration or strangulation of the displaced viscera.

Case presentation

A 47-year-old woman presented with dyspnea on exertion. Computed tomography revealed that a large part of the intestinal loop with superior mesenteric vessels and the right kidney were displaced into the right thoracic cavity. Preoperative three-dimensional (3D) simulation software visualized detailed anatomy of displaced viscera and the precise location and size of the diaphragmatic defect. She underwent elective surgery after concomitant pulmonary hypertension was stabilized preoperatively. The laparotomic approach was adopted. Malformation of the liver and the presence of intestinal malrotation were confirmed during the operation. The distal part of the duodenum, jejunum, ileum, colon, and right kidney were reduced into the abdominal cavity consecutively. A large-sized oval defect was closed with monofilament polypropylene mesh. No complications occurred postoperatively.

Conclusion

Symptomatic right-sided Bochdalek hernia in adults is exceedingly rare and is frequently accompanied by various visceral anomalies. Accurate diagnosis and appropriate surgical repair are crucial to prevent possible incarceration or strangulation. The preoperative 3D simulation provided comprehensive information on anatomy and concomitant anomalies and helped surgeons plan the operation meticulously and perform procedures safely.
Protocol for mapping psychosocial screening to resources in pediatric oncology: a pilot randomized controlled trial
Authors: Desjardins Leandra , Hancock Kelly , Szatmari Peter , Alexander Sarah , Shama Wendy , De Souza Claire , Mills Denise , Abla Oussama , Barrera Maru
Published: July 2021

Background

A pediatric cancer diagnosis and its treatment can have a detrimental effect on the mental health of children and their families. Screening to identify psychosocial risk in families has been recognized as a standard of care in pediatric oncology, but there has been limited clinical application of this standard thus far. A significant impediment to the implementation of psychosocial screening is the dearth of information on how to translate psychosocial screening to clinical practice, and specifically, how to follow-up from screening results. This manuscript aims to describe a protocol of a new intervention examining the feasibility and acceptability of mapping via a Psychosocial Navigator (PSN) psychosocial screening results to specific recommendations of resources for families based on measured risk for psychosocial distress and mental health symptoms.

Methods

The pilot randomized control trial (RCT) consists of dyads of youth (10–17 years) newly diagnosed with cancer and their primary caregiver. This RCT includes two arms (intervention and control group), with each group completing measurements near diagnosis and 1 year later. After the initial assessment, dyads in the intervention group receive monthly screening results and recommendations from the study PSN that are tailored to these results. The patient’s primary healthcare team (nurse, social worker, oncologist) also receive the risk, distress, and mental health results as well as the recommendations from the PSN.

Discussion

This study addresses a significant barrier to the implementation of psychosocial screening in pediatric oncology: specifically, the limited knowledge of how to follow-up from screening results. Findings from this pilot will inform a future definitive RCT to test the effectiveness of the intervention on patient and family mental health outcomes. This project has implications for enhancing clinical care in pediatric oncology, as well as other pediatric populations.

Strengths and limitations of this study

This is the first study of screening and follow-up using a psychosocial navigator.

This study involves both patient and caregiver report.

The small sample size necessitates a future larger study to investigate the effects of intervention.

Trial registration

NCT04132856, Registered 10 October 2019—retrospectively registered.
Surgery-first approach reduces the overall treatment time without damaging long-term stability in the skeletal class III correction: a preliminary study
Authors: Park Young-Wook , Kwon Kwang-Jun , Kang Yei-Jin , Jang In-San
Published: July 2021

Background

Compared to the conventional approach, including preoperative orthodontic preparation, the so-called surgery-first approach (SFA) seems to reduce the overall treatment time in the correction of skeletal class III dentofacial deformity. However, there have been controversies about postoperative skeletal stability with SFA. Therefore, we investigated the long-term stability and the overall treatment time after maxillomandibular surgery for skeletal class III correction with or without preoperative orthodontic preparation.

Methods

This retrospective study included eight patients who underwent maxillomandibular surgery for class III correction with the SFA (SFA group) and 20 patients who underwent the conventional approach (CA group). A comparative study of the change in the maxillary and mandibular position on preoperative (T1), 1-day (T2), 6-month (T3), and 2-year (T4) postoperative lateral cephalograms. We calculated the overall treatment time for each group.

Results

At the presurgical stage (T1), there was no bias in the skeletal features between the two groups. In the surgical change from T1 to T2, the mandible (point B) of the CA group was significantly moved superiorly. Short-term changes from T2 to T3 revealed that the mandible moved forward in both groups, whereas the maxillary position showed no significant changes. Long-term changes from T3 to T4 demonstrated that none of the measured parameters showed any significant differences. Finally, the average of overall treatment time was 15.1 months in the SFA group and 26.0 months in the CA group.

Conclusions

These findings suggest that SFA in bimaxillary orthognathic surgery for skeletal class III correction leads to predictable long-term skeletal stability, similar to surgery with CA. Furthermore, SFA reduced the overall treatment time compared to CA.
Linking scores on the 4- and 5-item versions of the Satisfaction with Life Scale in people with traumatic brain, spinal cord, or burn injury: a National Institute on Disability, Independent Living, and Rehabilitation Research Model System study
Authors: Bamer Alyssa M. , McMullen Kara , Deutsch Anne , Sevigny Mitch , Mroz Tracy , Wiechman Shelly A. , Schneider Jeffrey C. , Amtmann Dagmar
Published: July 2021

Background

The Satisfaction with Life Scale (SWLS) is a widely used measure of subjective well-being. Recent evidence indicates the fifth item of the scale reduces the reliability of the scale and is inappropriate for use in traumatic injury populations. The purpose of this study was to develop a linking procedure between the five-item version of the SWLS and a modified four-item version, which removes the problematic item, for use in Spinal Cord (SCI), Traumatic Brain (TBI), and Burn Injury populations.

Methods

Proration (i.e. adding the mean of the four items to their total) was identified as a potential linking solution that could be easily implemented in clinical or research settings. The validity of the proration approach was evaluated by examining mean differences, cross group classification by SWLS category, score correlations, the intraclass correlation coefficient, and visual inspection of Bland-Altman plots in a large sample of SCI, TBI, and Burn Injury survivors who were participants in the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) Model Systems’ National Databases.

Results

A total of 17,897 (SCI n = 8566, TBI n = 7941, and Burn n = 1390) participants were included in this study. SWLS scores ranged from 5 to 35, and the average score difference between directly derived and prorated scores was 0.39 points. A large majority of the sample (93%) had score differences of < 4 points (i.e. approximately 0.5 SD). The correlation between the prorated and directly derived scores was very high (r = 0.97) and the ICC value indicated excellent reliability (ICC = 0.97).

Conclusions

This study provides a valid scoring approach for researchers or clinicians who don’t want to lose continuity with previously collected data but prefer to switch to the modified four-item version of the SWLS. Clear guidance is provided for traumatic injury researchers or clinicians on how to implement the proration scoring approach.
Endophytic bacteria isolated from a weed plant as a potential biocontrol agent against stem end rot pathogen of pitaya in Vietnam
Authors: Trung Do Quang , Anh Luu The , Thuy Nguyen Thi , Van Dinh Mai , Hang Tran Thi
Published: July 2021

Background

Stem end rot (SER) disease caused by Alternaria alternata is one of the main fungal diseases in pitaya and other crops in Nam Dinh, Vietnam, that leads to extensive yield and economic losses. Biocontrol of SER, using endophytic bacteria, is environmentally friendly and compatible with other control measures. Hence, it is emerging as an alternative disease management strategy in sustainable agriculture. This study aimed to screen antagonistic bacteria isolated from the weed, Eleusine indica, with the potential to manage SER.

Results

A total of 16 endophytes were isolated from the stems, leaves, and roots of the weed, E. indica. Of those, 6 strains presented antagonistic effects against A. alternata growth, and one isolate, EI-15, showed a significant inhibitory effect on SER. In addition, analyzing the 16S rDNA sequence indicated that EI-15 was a strain of Bacillus amyloliquefaciens. Moreover, the results of the antagonistic spectrum assay showed that EI-15 significantly inhibited some plant and fruit tree pathogens, especially the suppression of A. alternata. Notably, the culture filtrate of strain EI-15 exhibited in vitro apparent activity against A. alternata. Furthermore, an in vivo antagonistic experiment of EI-15 on pitaya twig showed a significant reduction of lesion on twigs than the control.

Conclusions

Overall, this study suggested the potential application of the EI-15 strain as a biological agent and needs to be further studied in the field to control SER.
Characterization of the gut microbiome in wild rocky mountainsnails (Oreohelix strigosa)
Authors: Chalifour Bridget , Li Jingchun
Published: July 2021

Background

The Rocky Mountainsnail (Oreohelix strigosa) is a terrestrial gastropod of ecological importance in the Rocky Mountains of western United States and Canada. Across the animal kingdom, including in gastropods, gut microbiomes have profound effects on the health of the host. Current knowledge regarding snail gut microbiomes, particularly throughout various life history stages, is limited. Understanding snail gut microbiome composition and dynamics can provide an initial step toward better conservation and management of this species.

Results

In this study, we employed 16S rRNA gene amplicon sequencing to examine gut bacteria communities in wild-caught O. strigosa populations from the Front Range of Colorado. These included three treatment groups: (1) adult and (2) fetal snails, as well as (3) sub-populations of adult snails that were starved prior to ethanol fixation. Overall, O. strigosa harbors a high diversity of bacteria. We sequenced the V4 region of the 16S rRNA gene on an Illumina MiSeq and obtained 2,714,330 total reads. We identified a total of 7056 unique operational taxonomic units (OTUs) belonging to 36 phyla. The core gut microbiome of four unique OTUs accounts for roughly half of all sequencing reads returned and may aid the snails’ digestive processes. Significant differences in microbial composition, as well as richness, evenness, and Shannon Indices were found across the three treatment groups.

Conclusions

Comparisons of gut microbiomes in O. strigosa adult, fetal, and starved samples provide evidence that the host internal environments influence bacterial community compositions, and that bacteria may be transmitted vertically from parent to offspring. This work provides the first comprehensive report on the structure and membership of bacterial populations in the gastropod family Oreohelicidae and reveals similarities and differences across varying life history metrics. Strong differentiation between these life history metrics demonstrates the need for wider sampling for studies of dynamics of the snail gut microbiome.
The Clinical Sustainability Assessment Tool: measuring organizational capacity to promote sustainability in healthcare
Authors: Malone Sara , Prewitt Kim , Hackett Rachel , Lin John C. , McKay Virginia , Walsh-Bailey Callie , Luke Douglas A.
Published: July 2021

Background

Few validated assessment tools are available to increase understanding and measure factors associated with sustainment of clinical practices, an increasingly recognized need among clinicians. We describe the development of the Clinical Sustainability Assessment Tool (CSAT), designed to assess factors that contribute to sustainable practices in clinical settings.

Methods

Sixty-four participants from clinical and research fields participated in concept mapping and were recruited to brainstorm factors that lead to sustained clinical practices. Once repeated factors were removed, participants sorted items based on similarity and rated them by importance and feasibility. Using concept mapping analyses, items were grouped into meaningful domains to develop an initial tool. We then recruited pilot sites and early adopters, for a total of 286 practicing clinicians, to pilot and evaluate the tool. Individuals were recruited from clinical settings across pediatric and adult medical and surgical subspecialties. The data were analyzed using confirmatory factor analysis (CFA) to test hypothesized subscale structure in the instrument. We used root mean square error of approximation (RMSEA) and the standardized root mean square residual (SRMR) to assess fit and thus the ability of CSAT to measure the identified domains.

Results

The concept mapping produced sorted statements that were edited into items that could be responded to, resulting in the creation of a tool with seven determinant domains and 47 items. The pilot and CFA testing resulted in a final CSAT instrument made up 35 items, five per domain. CFA results demonstrated very good fit of the seven domain structure of the CSAT (RMSEA = 0.049; SRMR = 0.049). Usability testing indicated the CSAT is brief, easy to use, easy to learn, and does not require extensive training. Additionally, the measure scored highly (18/20) on the Psychometric and Pragmatic Evidence Rating Scale (PAPERS). The seven final CSAT domains were engaged staff and leadership, engaged stakeholders, organizational readiness, workflow integration, implementation and training, monitoring and evaluation, and outcomes and effectiveness.

Conclusions

The CSAT is a new reliable assessment tool which allows for greater practical and scientific understanding of contextual factors that enable sustainable clinical practices over time.
The Cognitive Walkthrough for Implementation Strategies (CWIS): a pragmatic method for assessing implementation strategy usability
Authors: Lyon Aaron R. , Coifman Jessica , Cook Heather , McRee Erin , Liu Freda F. , Ludwig Kristy , Dorsey Shannon , Koerner Kelly , Munson Sean A. , McCauley Elizabeth
Published: July 2021

Background

Implementation strategies have flourished in an effort to increase integration of research evidence into clinical practice. Most strategies are complex, socially mediated processes. Many are complicated, expensive, and ultimately impractical to deliver in real-world settings. The field lacks methods to assess the extent to which strategies are usable and aligned with the needs and constraints of the individuals and contexts who will deliver or receive them. Drawn from the field of human-centered design, cognitive walkthroughs are an efficient assessment method with potential to identify aspects of strategies that may inhibit their usability and, ultimately, effectiveness. This article presents a novel walkthrough methodology for evaluating strategy usability as well as an example application to a post-training consultation strategy to support school mental health clinicians to adopt measurement-based care.

Method

The Cognitive Walkthrough for Implementation Strategies (CWIS) is a pragmatic, mixed-methods approach for evaluating complex, socially mediated implementation strategies. CWIS includes six steps: (1) determine preconditions; (2) hierarchical task analysis; (3) task prioritization; (4) convert tasks to scenarios; (5) pragmatic group testing; and (6) usability issue identification, classification, and prioritization. A facilitator conducted two group testing sessions with clinician users (N = 10), guiding participants through 6 scenarios and 11 associated subtasks. Clinicians reported their anticipated likelihood of completing each subtask and provided qualitative justifications during group discussion. Following the walkthrough sessions, users completed an adapted quantitative assessment of strategy usability.

Results

Average anticipated success ratings indicated substantial variability across participants and subtasks. Usability ratings (scale 0–100) of the consultation protocol averaged 71.3 (SD = 10.6). Twenty-one usability problems were identified via qualitative content analysis with consensus coding, and classified by severity and problem type. High-severity problems included potential misalignment between consultation and clinical service timelines as well as digressions during consultation processes.

Conclusions

CWIS quantitative usability ratings indicated that the consultation protocol was at the low end of the “acceptable” range (based on norms from the unadapted scale). Collectively, the 21 resulting usability issues explained the quantitative usability data and provided specific direction for usability enhancements. The current study provides preliminary evidence for the utility of CWIS to assess strategy usability and generate a blueprint for redesign.
Understanding the need for a whole-of-society approach in school nutrition policy implementation: a qualitative analysis
Authors: Sobers Natasha P. , Bishop Lisa , Ng Shu Wen , Soares-Wynter Suzanne , Greaves Natalie S. , Murphy Madhuvanti M.
Published: July 2021

Background

Only three of twenty Caribbean Community (CARCICOM) countries have mandatory school nutrition policies despite one third of the region’s children being overweight or obese. In Barbados, there are nutrition guidelines which lack the legal mandate of a formal policy. We aim to assess the comprehensiveness of current national nutrition guidelines and to understand the factors operating in the inner and outer school setting that may influence the implementation of a mandatory school nutrition policy from the perspectives of school administrators.

Methods

A documentary analysis of existing nutritional guidelines was conducted along with qualitative semi-structured interviews in primary (elementary) and secondary (high) schools in Barbados. We purposively sampled six primary and four secondary school administrators (principals, deputy principals or senior teachers) to explore their knowledge and views on the National School Nutrition Guidelines. The deterministic implementation paradigm, Consolidated Framework for Implementation (CFIR), was used to explore the complexities within the inner and outer settings of schools. Documentary analysis used a theory-based framework informed by the Wellness School Assessment Tool—school policy analysis questionnaire. Interview transcripts were team coded using thematic analysis with constant comparison facilitated by NVIVO software version12.

Results

School administrators were unaware of the existing National School Nutrition Guidelines which documentary analysis found to be restrictive and weak for implementation. Administrators envisioned a government-led (outer setting), whole of society approach as the most effective strategy for the development and implementation of a proposed mandatory school nutrition policy. School administrators identified lack of financial and human resources as barriers to nutrition policy implementation. Formal and informal food vendors are institutionalized in schools and are influential determinants of the school food environment. Schools have individually reached into the outer setting to work with civil society organizations and private individuals to provide financial support and nutrition expertise to their institutions. Mass media campaigns in the outer setting may influence child and parental food choices.

Conclusion

School administrators describe that government-led, CSO supported policy development using a whole-of-society approach has implications for improving nutrition policy implementation. Our findings demonstrate the use of a deterministic implementation framework in the pre-implementation phase of school nutrition policy development.
Financial literacy and financial behavior with the mediating effect of family financial socialization in the financial institutions of Lahore, Pakistan
Authors: Khawar Sumaira , Sarwar Aamir
Published: July 2021

Purpose

The main purpose of this study was to find out the relationship between financial literacy and financial behavior and to discover the mediating influence of family financial socialization on this relationship. The study also particularizes that how personal knowledge of finance of an employee and whatever they have learned through family socialization will help them to make sound decisions having a financial impact on them and their family.

Design/methodology/approach

Employees of financial institutions employed and residing in Lahore, Pakistan, were the target population of this report. It was a cross-sectional quantitative research study. By using a detailed questionnaire, primary data were obtained. The sample size was 330; through convenience sampling, employees employed in banks were chosen. Descriptive analysis, parametric test, reliability test, and correlational examination with the aid of SPSS 23 and the use of SmartPLS 3.0. are knowledge investigation techniques used in this examination study to infer outcomes.

Results/findings

The outcomes which are created from this exploration include: (1) there was no distinction in the financial conduct of representatives from various socioeconomics gatherings. Financial education has a critical positive relationship with financial behavior. (2) Family financial socialization additionally shows a huge positive relationship with financial education and financial behavior. (3) Financial education demonstrated a remarkable abnormal impact on financial behavior through family financial socialization. (4) Family financial socialization shows partial mediation between financial literacy and financial behavior. We can accomplish that formal, as well as informal, training of finance decides the financial behavior of people.

Originality/value

This study is the first of this kind to examine the association between financial literacy, and financial behavior using family financial socialization as a mediator and employees of financial institutions as the target population.
Complications of cochlear implantation surgery in Zagazig University Hospitals
Authors: Elfeky Alaa Eldin M. , Tantawy Adly A. , Ibrahim Asmaa M. , Saber Ibrahim M. , Abdel-Monem Said
Published: July 2021

Background

Cochlear implantation (CI) has been established worldwide as the surgical treatment for individuals with bilateral severe to profound hearing loss. Complications due to surgery are minimal and are often encountered in cases with congenital anomalies of the temporal bone and inner ear. Complications in CI are related to malfunctioning of the device or the process of wound healing. In most cochlear implant centers, as the surgeon’s skill and clinical expertise in managing various cochlear implant cases improve with years of experience, the complication rates ideally come down over time.

This article is intended to describe the most common surgical complications of cochlear implantation in Zagazig University Hospitals. This retrospective study included 130 patients who underwent cochlear implantation in Zagazig University Hospitals from 2016 to 2018. The patients were 61 males and 69 females; their ages ranged between 2 and 6 years old with a mean age of 4.3. This study aims to provide feedback on the common complications of CI surgery at our institution to help the reduction of its incidence in the future.

Results

One hundred thirty cases of cochlear implants were performed in our department between 2016 and 2018. Sixty complications were recorded, including 27 cases of minor and 21 cases of major complications. Minor complications were flap wound infection in 4 cases (3.1%), chorda tympani nerve injury in 7 cases (5.4%), postoperative vertigo and vomiting in 3 cases (2.3%), injury of EAC in 7 cases (5.4%), wound seroma/hematoma in 4 cases (3.1%), and facial nerve twitching in 2 cases (1.5%). Major complications were electrode extrusion in 2 cases (1.5%), CSOM in 1 case (0.8%), CSF leak in 8 cases (6.1%), magnet migration in 3 cases (2.3%), total facial nerve paralysis in 5 cases (3.8%), and device failure in 2 cases (1.5%).

Conclusion

The overall incidence of major complications is low. The majority of minor complications can be effectively managed with conservative measures. Cochlear implantation remains a safe and effective surgical procedure.
BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer
Authors: Tao Yubing , Wang Fei , Shen Xiaopei , Zhu Guangwu , Liu Rengyun , Viola David , Elisei Rossella , Puxeddu Efisio , Fugazzola Laura , Colombo Carla , Jarzab Barbara , Czarniecka Agnieszka , Lam Alfred K , Mian Caterina , Vianello Federica , Yip Linwah , Riesco-Eizaguirre Garcilaso , Santisteban Pilar , O’Neill Christine J , Sywak Mark S , Clifton-Bligh Roderick , Bendlova Bela , Sýkorová Vlasta , Zhao Shihua , Wang Yangang , Xing Mingzhao
Published: July 2021

Context

How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined.

Objective

To study whether BRAF V600E affected LNM-associated mortality in PTC.

Design, Setting, and Participants

We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months.

Results

Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism.

Conclusions

LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.
White Matter Microstructural Differences in Youth With Classical Congenital Adrenal Hyperplasia
Authors: Cotter Devyn L , Azad Anisa , Cabeen Ryan P , Kim Mimi S , Geffner Mitchell E , Sepehrband Farshid , Herting Megan M
Published: July 2021

Context

Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH.

Objective

To examine brain white matter microstructure in youth with CAH compared to controls.

Design

A cross-sectional sample of 23 youths with CAH due to 21-hydroxylase deficiency (12.9 ± 3.5 year; 61% female) and 33 healthy controls (13.1 ± 2.8 year; 61% female) with 3T multishell diffusion-weighted magnetic resonance brain scans.

Main Outcome Measures

Complementary modeling approaches, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to examine in vivo white matter microstructure in six white matter tracts that innervate the prefrontal and subcortical regions.

Results

DTI showed CAH youth had lower fractional anisotropy in both the fornix and stria terminalis and higher mean diffusivity in the fornix compared to controls. NODDI modeling revealed that CAH youth have a significantly higher orientation dispersion index in the stria terminalis compared to controls. White matter microstructural integrity was associated with smaller hippocampal and amygdala volumes in CAH youth.

Conclusions

These patterns of microstructure reflect less restricted water diffusion likely due to less coherency in oriented microstructure. These results suggest that white matter microstructural integrity in the fornix and stria terminalis is compromised and may be an additional related brain phenotype alongside affected hippocampus and amygdala neurocircuitry in individuals with CAH.
Ex Vivo Intact Tissue Analysis Reveals Alternative Calcium-sensing Behaviors in Parathyroid Adenomas
Authors: Koh James , Zhang Run , Roman Sanziana , Duh Quan-Yang , Gosnell Jessica , Shen Wen , Suh Insoo , Sosa Julie A
Published: July 2021

Context

The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood.

Objective

This study aimed to define parathyroid tumor biochemical properties associated with calcium-sensing failure in PHPT patients, and to relate differences in these profiles to variations in clinical presentation.

Methods

Preoperative clinical data from a sequential series of 39 patients undergoing surgery for PHPT at an endocrine surgery referral center in a large, public university hospital were evaluated for correlation to parathyroid tumor biochemical behavior. An intact tissue, ex vivo interrogative assay was employed to evaluate the calcium-sensing capacity of parathyroid adenomas relative to normal donor glands. Tumors were functionally classified based on calcium dose-response curve profiles, and clinical parameters were compared among the respective classes. Changes in the relative expression of 3 key components in the calcium/parathyroid hormone (PTH) signaling axis—CASR, RGS5, and RCAN1—were evaluated as potential mechanisms for calcium-sensing failure.

Results

Parathyroid adenomas grouped into 3 distinct functional classes. Tumors with diminished calcium sensitivity were the most common (18 of 39) and were strongly associated with reduced bone mineral density (P = 0.0009). Tumors with no calcium-sensing deficit (11 of 39) were associated with higher preoperative PTH (P = 0.036). A third group (6/39) displayed a nonsigmoid calcium/PTH response curve; 4 of these 6 tumors expressed elevated RCAN1.

Conclusion

Calcium-sensing capacity varies among parathyroid tumors but downregulation of the calcium-sensing receptor (CASR) is not an obligate underlying mechanism. Differences in tumor calcium responsiveness may contribute to variations in PHPT clinical presentation.
Analysis of Expression of Different Histone Deacetylases in Autoimmune Thyroid Disease
Authors: Sacristán-Gómez Pablo , Serrano-Somavilla Ana , González-Amaro Roberto , Martínez-Hernández Rebeca , Marazuela Mónica
Published: July 2021

Context

Histone deacetylases (HDACs) and histone acetyltransferases (HAT) have an important role in the regulation of gene transcription as well as in the development and function of CD4+Foxp3+ T regulatory (Treg) cells. Our group and others have reported that patients with autoimmune thyroid disease (AITD) show abnormalities in the levels and function of different Treg cell subsets.

Objective

We aimed to analyze the levels of expression of several HDACs and the Tip60 HAT in the thyroid gland and immune cells from patients with AITD.

Methods

The expression of HDAC1-11 and the Tip60 HAT, at RNA and protein levels, were determined in thyroid tissue from 20 patients with AITD and 10 healthy controls and these findings were correlated with clinical data. HDAC9 and Tip60 levels were also analyzed in thyroid cell cultures, stimulated or not with proinflammatory cytokines, as well as in different cell subsets from peripheral blood mononuclear cells.

Results

Altered expression of different HDACs was observed in thyroid tissue from AITD patients, including a significant increase in HDAC9, at RNA and protein levels. Likewise, HDAC9 expression was increased in peripheral blood mononuclear cells particularly in Treg cells in patients with AITD. In contrast, Tip60 expression was reduced in thyroid gland samples from patients with Hashimoto thyroiditis.

Conclusion

Our results indicate that HDAC expression is dysregulated in thyroid gland and immune cells from patients with AITD, suggesting involvement in the pathogenesis of this condition.
Migration, Gestational Diabetes, and Adverse Pregnancy Outcomes: A Nationwide Study of Singleton Deliveries in Denmark
Authors: Kragelund Nielsen Karoline , Andersen Gregers Stig , Damm Peter , Nybo Andersen Anne-Marie
Published: July 2021

Context

It remains unclear if migrants have different odds for adverse outcomes associated with gestational diabetes mellitus (GDM).

Objective

We investigated if the associations between GDM and adverse pregnancy outcomes are modified by country of origin and examined the odds of these outcomes according to GDM status and country of origin.

Methods

Data were extracted from a nationwide register-based study of singleton deliveries in Denmark, 2004-2015. We used logistic regression models and tested for interaction.

Results

Among the 710 413 singleton deliveries, 2.6% had GDM and 14.4% were immigrants. Country of origin modified the association between GDM and pre-eclampsia, large for gestational age (LGA), and small for gestational age (SGA) but not between GDM and planned or emergency cesarean section and preterm delivery. GDM increased the risk of pre-eclampsia among women from Denmark (OR 1.28; 95% CI, 1.18-1.39), Lebanon (OR 3.34; 95% CI, 1.35-8.26), and Morocco (OR 2.28; 95% CI, 1.16-6.88). GDM was associated with increased odds of LGA among women from most countries, particularly women from Sri Lanka (OR 4.20; 95% CI, 2.67-6.61), and was associated with reduced odds of SGA in some countries. Compared with Danish-born women with GDM, the odds of LGA were significantly lower and the odds of SGA higher among women with GDM from India, Lebanon, Pakistan, Iraq, and Somalia.

Conclusions

Our study documents that different immigrant groups have higher odds of different GDM-associated adverse pregnancy outcomes and also among countries of origin often grouped together. This highlights the importance of increased awareness to both immigrant background and GDM status in the clinical assessment.
Weekly Lonapegsomatropin in Treatment–Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial
Authors: Thornton Paul S , Maniatis Aristides K , Aghajanova Elena , Chertok Elena , Vlachopapadopoulou Elpis , Lin Zhengning , Song Wenjie , Christoffersen Eva Dam , Breinholt Vibeke Miller , Kovalenko Tatiana , Giorgadze Elene , Korpal-Szczyrska Maria , Hofman Paul L , Karpf David B , Shu Aimee D , Beckert Michael
Published: July 2021

Context

For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD.

Objective

The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin.

Design

The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727).

Setting

This trial took place at 73 sites across 15 countries.

Patients

This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD.

Interventions

Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily.

Main Outcome Measure

The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS).

Results

Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups.

Conclusions

The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.
Insulin: A 100-Year-Old Discovery With a Fascinating History
Authors: Rostène William , De Meyts Pierre
Published: July 2021

Diabetes has been known since antiquity. We present here a historical perspective on the concepts and ideas regarding the physiopathology of the disease, on the progressive focus on the pancreas, in particular on the islets discovered by Langerhans in 1869, leading to the iconic experiment of Minkowski and von Mering in 1889 showing that pancreatectomy in a dog induced polyuria and diabetes mellitus. Subsequently, multiple investigators searched for the active substance of the pancreas and some managed to produce extracts that lowered blood glucose and decreased polyuria in pancreatectomized dogs but were too toxic to be administered to patients. The breakthrough came 100 years ago, when the team of Frederick Banting, Charles Best, and James Collip working in the Department of Physiology headed by John Macleod at the University of Toronto managed to obtain pancreatic extracts that could be used to treat patients and rescue them from the edge of death by starvation, the only treatment then available. This achievement was quickly recognized by the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923. At 32, Banting remains the youngest awardee of this prize. Here we discuss the work that led to the discovery and its main breakthroughs, the human characters involved in an increasingly dysfunctional relationship, the controversies that followed the Nobel Prize, and the debate as to who actually “discovered” insulin. We also discuss the early commercial development and progress in insulin crystallization in the decade or so following the Nobel Prize.
Measurement of Peak C-Peptide at Diagnosis Informs Glycemic Control but not Hypoglycemia in Adults With Type 1 Diabetes
Authors: Carr Alice L J , Oram Richard A , Marren Shannon M , McDonald Timothy J , Narendran Parth , Andrews Robert C
Published: July 2021

Context

High-residual C-peptide in longer-duration type 1 diabetes (T1D) is associated with fewer hypoglycemic events and reduced glycemic variability. Little is known about the impact of C-peptide close to diagnosis.

Objective

Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with T1D, we aimed to explore if variation in C-peptide close to diagnosis influenced glycemic variability and risk of hypoglycemia.

Methods

We studied newly diagnosed adults with T1D who wore a Dexcom G4 CGM for 7 days as part of the Exercise in Type 1 Diabetes (EXTOD) study. We examined the relationship between peak stimulated C-peptide and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants.

Results

For every 100 pmol/L-increase in peak C-peptide, the percentage of time spent in the range 3.9 to 10 mmol/L increased by 2.4% (95% CI, 0.5-4.3), P = .01) with a reduction in time spent at level 1 hyperglycemia (> 10 mmol/L) and level 2 hyperglycemia (> 13.9 mmol/L) by 2.6% (95% CI, –4.9 to –0.4, P = .02) and 1.3% (95% CI, –2.7 to –0.006, P = .04), respectively. Glucose levels were on average lower by 0.19 mmol/L (95% CI, –0.4 to 0.02, P = .06) and SD reduced by 0.14 (95% CI, –0.3 to –0.02, P = .02). Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia (P = .97) or hypoglycemic risk (P = .72). There was no association between peak C-peptide and insulin dose–adjusted glycated hemoglobin A1c (P = .45).

Conclusion

C-peptide is associated with time spent in the normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with T1D.
Possibilities for new social work professional resistance in Chile: times of social change?
Authors: Reininger Taly , Muñoz-Arce Gianinna , Villalobos Cristobal
Published: July 2021

In the current unscrupulous neoliberal climate, social workers are increasingly confronted with ethical and political tensions that clash with the profession’s commitments to human rights and social justice. However, despite neoliberalism’s global reach, the scholarship on social work professional resistance has been largely limited to the Global North. Taking into consideration this absence in the literature, this article seeks to explore the possibilities for professional resistance in the Global South, specifically, in Chile, a country in which neoliberalism was forcefully imposed and that has experienced an exponential growth in social movements over the past two decades. The following article explores the structural and material conditions that have historically shaped social work resistances, arguing that the current social and political climate, specifically, the constitutional process under way, presents a space from which new resistances are possible and necessary in order to challenge neoliberal hegemony.
Optical links on silicon photonic chips using ultralow-power consumption photonic-crystal lasers
Authors: Takeda Koji , Tsurugaya Takuma , Fujii Takuro , Shinya Akihiko , Maeda Yoshiho , Tsuchizawa Tai , Nishi Hidetaka , Notomi Masaya , Kakitsuka Takaaki , Matsuo Shinji
Published: July 2021

Ultrashort-distance optical interconnects are becoming increasingly important due to continuous improvements in servers and high-performance computers. As light sources in such interconnects, directly modulated semiconductor lasers with an ultrasmall active region are promising. In addition, using Si waveguides is important to provide low loss optical links with functions such as wavelength filtering and switching. In this paper, we demonstrate a wafer-scale heterogeneous integration of lambda-scale embedded active-region photonic-crystal (LEAP) lasers and Si waveguides, achieved through precise alignment. We numerically and experimentally demonstrated the coupling design between the LEAP lasers and Si waveguides; it is important to match propagation constants of Si waveguides and wavenumber of the optical cavity modes. The LEAP lasers exhibit an ultralow threshold current of 13.2-μA and 10-Gbit/s direct modulation. We also achieved the first data transmission using an optical link consisting of a LEAP laser, Si waveguide, and photodetector and obtained an averaged eye diagram at a bit rate of 10 Gbit/s with a bias current of 150 μA.