bluuebunny/crossref_metadata_2025 huggingface dataset:
Autistic children and adolescents with frequent restricted interest and repetitive behavior showed more difficulty in social cognition during mask-wearing during the COVID-19 pandemic: a multisite survey
Authors: Tamon Hiroki , Itahashi Takashi , Yamaguchi Sosei , Tachibana Yoshiyuki , Fujino Junya , Igarashi Miki , Kawashima Makiko , Takahashi Riina , Shinohara Nozomi A. , Noda Yoshihiro , Nakajima Shinichiro , Hirota Tomoya , Aoki Yuta Y.
Published: September 2022

Background

The public health measures enacted in order to control the coronavirus disease (COVID-19) pandemic have caused considerable changes to daily life. For autistic children and adolescents, adapting to the “new normal,” including mask-wearing, may be difficult because of their restricted interest and repetitive behavior (RRB) characteristics. We aimed to examine the relationships between RRB characteristics and the impact of mask-wearing on their social communications during the pandemic.

Methods

We recruited participants with a clinical diagnosis of autism spectrum disorder based on DSM-5 diagnostic criteria from two outpatient clinics in Tokyo, Japan, between November 2020 and April 2021 using a convenience sampling methodology. As a result, the participants consisted of 102 children and adolescents (mean (SD) age = 11.6 (5.3)). We collected data on RRB characteristics frequency before and during the pandemic using the CoRonavIruS Health Impact Survey (CRISIS) – Adapted for Autism and Related Neurodevelopmental conditions (AFAR). We then conducted factor analyses to compute the RRB severity composite scores, which are divided into lower- (e.g., sensory seeking), and higher-order (e.g., restricted interest). We also investigated mask-wearing culture using a bespoke questionnaire, and using Spearman’s rank correlation analyses, we examined the relationships between before pandemic RRB characteristics, and the impact of mask-wearing on social communications during the pandemic.

Results

We found that children and adolescents who exhibited lower-order RRB before the pandemic had difficulties in going-out with mask-wearing (rho = -0.25, q = .031), more challenges with mask-wearing (rho =  − 0.34, q = .0018), and difficulty in referring to others’ emotions while wearing masks (rho =  − 0.36, q = .0016). We also found an association between higher-order RRB before the pandemic and an uncomfortable sensation (rho =  − 0.42, q = .0002) and difficulties in referring to other’s emotions while wearing masks (rho =  − 0.25, q = .031).

Conclusions

We revealed that various behaviors, such as sensory seeking, repetitive motor mannerisms and movements, and rituals and routines, undertaken before the pandemic could be important predictors of difficulties with mask-wearing and social communication for autistic children and adolescents during the pandemic. Caregivers and teachers wearing masks may need to provide extra support for social communication to autistic children and adolescents showing RRB characteristics frequently.
Fistula between the rectal stump and left iliac artery
Authors: Alshammari Mariam , Fatani Jumana , Alotaibi Ohood , Alhajri Khalid , Terro Khalil
Published: September 2022

Background

Isolated iliac artery aneurysms are rare and difficult to diagnose. It is more common in males. It can be asymptomatic at diagnosis or can present with frank rupture, or symptoms caused by compression on nearby organs.

Case presentation

A 44 years old male was diagnosed with rectosigmoid adenocarcinoma and underwent low anterior resection. One year after the surgery, he presented with fistula between the rectal stump and left iliac artery that was managed by stenting.

Conclusion

A fistula between the rectal stump and the left iliac artery is very rare. There are several treatment options for ilio-rectal fistula but no conclusive specific treatment.
Association of sleep duration and insomnia with metabolic syndrome and its components in the Women’s Health Initiative
Authors: Peila Rita , Xue Xiaonan , Feliciano Elizabeth M. Cespedes , Allison Matthew , Sturgeon Susan , Zaslavsky Oleg , Stone Katie L. , Ochs-Balcom Heather M. , Mossavar-Rahmani Yasmin , Crane Tracy E. , Aggarwal Monica , Wassertheil-Smoller Sylvia , Rohan Thomas E.
Published: September 2022

Background

Epidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women’s Health Initiative (WHI).

Methods

The study included postmenopausal women (ages 50–79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated.

Results

In cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12–2.04), while sleep duration of 8- < 9 h was associated with waist circumference > 88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01–1.40 and OR = 1.23; 95%CI 1.05–1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99–1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03–1.34 and OR = 1.17; 95%CI 1.02–1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01–1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08–2.03).

Conclusions

Among postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.
Proton beam therapy for the isolated recurrence of endometrial cancer in para-aortic lymph nodes: a case report
Authors: Uno Kaname , Yoshihara Masato , Tano Sho , Takeda Takehiko , Kishigami Yasuyuki , Oguchi Hidenori
Published: September 2022

Background

Proton beam therapy penetrates tumor tissues with a highly concentrated dose. It is useful when normal structures are too proximate to the treatment target and, thus, may be damaged by surgery or conventional photon beam therapy. However, proton beam therapy has only been used to treat recurrent endometrial cancer in a few cases; therefore, its effectiveness remains unclear.

Case presentation

We herein report a case of the isolated recurrence of endometrial cancer in the para-aortic lymph nodes in a 59-year-old postmenopausal woman that was completely eradicated by proton beam therapy. The patient was diagnosed with stage IIIC2 endometrial cancer and treated with 6 courses of doxorubicin (45 mg/m2) and cisplatin (50 mg/m2) in adjuvant chemotherapy. Fifteen months after the initial therapy, the isolated recurrence of endometrial cancer was detected in the para-aortic lymph nodes. The site of recurrence was just under the left renal artery. Due to the potential risks associated with left kidney resection due to the limited surgical space between the tumor and left renal artery, proton beam therapy was administered instead of surgery or conventional photon beam therapy. Following proton beam therapy, the complete resolution of the recurrent lesion was confirmed. No serious complications occurred during or after treatment. There have been no signs of recurrence more than 7 years after treatment.

Conclusions

Proton beam therapy is a potentially effective modality for the treatment of recurrent endometrial cancer where the tumor site limits surgical interventions and the use of conventional photon beam therapy.
Measuring inequality in the distribution of health human resources using the Hirschman-Herfindahl index: a case study of Qazvin Province
Authors: Nasiri Asghar , Yusefzadeh Hasan , Amerzadeh Mohammad , Moosavi Saeideh , Kalhor Rohollah
Published: September 2022

Background

Achieving equity in the distribution of health services is one major goal in the health system. This study aimed to determine equality in distributing health human resources (physicians) in the Qazvin University of Medical Sciences before and after the Health Transformation Plan (HTP) based on the Hirschman-Herfindahl index (HHI).

Methods

In this descriptive-analytical study, the statistical population was general practitioners (GPs), specialists and subspecialists in the Qazvin University of Medical Sciences from 2011-to 2017. We extracted demographic statistics of the cities from the Statistical Center of Iran. Physicians’ statistics were obtained from the Curative Affairs Deputy at the Qazvin University of Medical Sciences. We assessed inequality using the HHI.

Results

The highest number of GPs was in 2014, and specialists and subspecialists were in 2017. The lowest number of GPs, specialists, and subspecialists were in 2016, 2011 and 2015. The HHI for GPs in 2011–2017 was between 4300 and 5200. The lowest concentration for specialists before the HTP plan was the cardiologist with 3300, and after the HTP, the internal specialist with 3900. Also, the numerical value of this index for all subspecialty physicians after the HTP was 10,000, the highest level of concentration.

Conclusion

The values obtained from the HHI index indicate the high concentration and disproportionate and inequitable distribution of human resources in the health sector in this province. The number of specialists in some cities is still much less than acceptable, and some cities even have shortcomings in the critical specialists.
Hierarchical clock-scale hand-drawn mapping as a simple method for bronchoscopic navigation in peripheral pulmonary nodule
Authors: Zhong Chang-Hao , Su Zhu-Quan , Luo Wei-Zhan , Rao Wan-Yuan , Feng Jia-Xin , Tang Chun-Li , Chen Yu , Chen Xiao-Bo , Fan Ming-Yue , Li Shi-Yue
Published: September 2022

Background

A feasible and economical bronchoscopic navigation method in guiding peripheral pulmonary nodule biopsy is lacking.

Objective

To investigate the utility of hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules.

Methods

We developed a hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Patients with peripheral pulmonary nodules were recruited and assigned to two groups in this retrospective study, subjects in VBN group received conventional bronchoscopy in conjunction with virtual bronchoscopic navigation (VBN) and radial probe endobronchial ultrasound (RP-EBUS) for biopsy (VBN group), while HBN group underwent ultrathin bronchoscopy and RP-EBUS under the guidance of hand-drawn bronchoscopic navigation (HBN). The demographic characteristics, procedural time, operating cost and diagnostic yield were compared between these two groups.

Results

Forty-eight patients with peripheral pulmonary nodule were enrolled in HBN group, while 42 in VBN group. There were no significant differences between VBN and HBN groups in terms of age, gender, lesion size, location and radiographic type. The time of planning pathway (1.32 vs. 9.79 min, P < 0.001) and total operation (23.63 vs. 28.02 min, P = 0.002), as well as operating cost (758.31 ± 125.21 vs.1327.70 ± 116.25 USD, P < 0.001) were markedly less in HBN group, compared with those in VBN group. The pathological diagnostic efficiency of benign and malignant disease in HBN group appeared similar with those in VBN group, irrespective of the size of pulmonary lesion (larger or smaller than 20 mm). The total diagnostic yield of HBN had no marked difference from that of VBN (75.00% vs. 61.90%, P = 0.25).

Conclusions

Hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation could serve as a feasible and economical method for guiding peripheral pulmonary nodule biopsy, providing a comparable diagnostic yield in comparison with virtual bronchoscopic navigation.
Diagnosis of Apis dorsata venom allergy: use of recombinant allergens of Apis mellifera and a passive basophil activation test
Authors: Gunasekara Peshala , Handunnetti S. M. , Premawansa Sunil , Witharana E. W. R. A. , Ratnayake Indra P. , Kaluarachchi Pradeep , Karunatilake Chandima , Dias R. K. S. , Premakumara G. A. S. , Dasanayake W. M. D. K. , Seneviratne Suranjith L. , de Silva Rajiva
Published: September 2022

Background

Allergy toApis dorsata(Giant Asian Honeybee) venom is the commonest insect allergy in Sri Lanka and South East Asia. However, laboratory diagnosis is difficult as the pure venom and diagnostic reagents are not commercially available.

Objective

This study assessed the use of four recombinant allergens ofA. melliferavenom and the passive basophil activation test in the diagnosis ofA. dorsatavenom anaphylaxis.

Methods

Serum IgE levels to four recombinant allergens ofA. mellifera, rApi m 1, 2, 5 and 10 were assessed and compared with serum IgE to the crude venom ofA. melliferaorV. vulgarisby Phadia ImmunoCAP, in patients who developed anaphylaxis toA. dorsatastings. Basophil activation in response to venom ofA. dorsataorV. affiniswas assessed using a passive basophil activation test. Association of the severity of the reaction with basophil activation was compared.

Results

rApi m 1 and 10 combinedly had significant correlation (r = 0.722; p < 0.001) with the crude venom ofA. mellifera(Western honeybee) and a higher positivity rate of 90% (27/30). Whereas, IgE reactivity to rApi m 2 or 5 had significant correlation (p = 0.02 and p = 0.005 respectively) withV. vulgariscrude venom. All 30 (100%) were positive toA. dorsatavenom in passive BAT; 70% (21/30) had over 80% activation, 96.7% (29/30) had over 60% activation and 100% had over 50% activation. Percentage activation of basophils in patients who had mild or moderate reactions (n = 20) was significantly low (p = 0.02) from that of patients who had severe reactions (n = 10).

Conclusions

rApi m 1 and 10 when combined was sensitive for the diagnosis ofA. dorsataallergy. This combination had the lowest cross-reactivity rate withVespula vulgaris. The passive BAT is highly sensitive inA. dorsataallergy. The basophil reactivity was significantly higher in severe anaphylaxis compared to mild/moderate anaphylaxis. This finding should be further explored in further studies.
The efficacy of a multi-strategy choice architecture intervention on improving the nutritional quality of high school students’ lunch purchases from online canteens (Click & Crunch High Schools): a cluster randomized controlled trial
Authors: Delaney Tessa , Yoong Sze Lin , Lamont Hannah , Lecathelinais Christophe , Wolfenden Luke , Clinton-McHarg Tara , Sutherland Rachel , Wyse Rebecca
Published: September 2022

Background

High school canteens are an ideal setting for public health nutrition intervention, and choice architecture strategies that facilitate the purchase of healthier foods and beverages from school canteens are recommended by the World Health Organization. The rapid uptake of online lunch ordering within school canteens provides a unique opportunity to implement choice architecture strategies that support healthier food choices with high fidelity. Despite this, no trial has tested the efficacy of choice architecture strategies within an online lunch ordering system on improving the nutritional quality of high school student lunch purchases. The objective of this study was to assess the impact of embedding choice architecture strategies into an online lunch ordering system on the nutritional quality of the school canteen lunch purchases of high school students (aged 12–19 years).

Methods

A cluster randomized controlled trial was conducted with nine high schools in one Australian state. Schools were randomized to receive either a 2-month choice architecture intervention (involving menu labelling, prompts, item positioning, and feedback), or usual online ordering. Nutrient quality of online canteen lunch purchases was assessed using routine data collected by the online ordering system. Primary outcomes were the proportion of ‘Everyday’, ‘Occasional’, and ‘Should not be sold’ items purchased, categorized using the state healthy canteen policy. Secondary outcomes were the mean energy, saturated fat, sugar, and sodium content of purchases and the mean weekly revenue from online lunch orders. Linear mixed models were analyzed to assess outcomes.

Results

Analysis of the student cohort (Intervention: 4 schools, 656 students; Control:5 schools, 675 students) showed significant between group differences over time for the intervention group for the mean percentage of online lunch items per student that were ‘Everyday’ (+ 5.5%;P < 0.001) and ‘Should not be sold’ (− 4.4%;P < 0.001). There were no between group differences over time in the mean percentage of online lunch items that were ‘Occasional’; the average energy, saturated fat, sugar, or sodium content of lunch orders. There was also no difference in mean weekly revenue from high school student online lunch orders (P = 0.23).

Conclusions

These findings suggest that a low intensity, choice architecture intervention embedded within an online ordering system can increase the purchase of healthier food items for high school students in one Australian state without any adverse impact on canteen revenue.

Trial registration

This trial was prospectively registered on Open Science Framework on 23rd October 2020 as osf.io/h8zfr.
Effects of intervention combining transcranial direct current stimulation and foot core exercise on sensorimotor function in foot and static balance
Authors: Xiao Songlin , Wang Baofeng , Yu Changxiao , Shen Bin , Zhang Xini , Ye Dongqiang , Deng Liqin , Xu Yongxin , Zhou Junhong , Fu Weijie
Published: September 2022

Objective

This study aimed to examine the effects of combining transcranial direct current stimulation (tDCS) and foot core exercise (FCE) on the sensorimotor function of the foot (i.e., toe flexor strength and passive ankle kinesthesia) and static balance.

Methods

In this double-blinded and randomized study, 30 participants were randomly assigned into two groups: tDCS combined with FCE and sham combined with FCE (i.e., control group). The participants received 2 mA stimulation for 20 min concurrently with FCE over 4 weeks (i.e., three sessions per week). After the first two groups completed the intervention, a reference group (FCE-only group) was included to further explore the placebo effects of sham by comparing it with the control group. Foot muscle strength, passive ankle kinesthesia, and static balance were assessed at baseline and after the intervention.

Results

Compared with the control group and baseline, tDCS combined with FCE could increase toe flexor strength (p < 0.001) and decrease the passive kinesthesia threshold of ankle eversion (p = 0.002). No significant differences in static balance were observed between tDCS + FCE and control groups. The linear regression models showed an association towards significance between the percent changes in metatarsophalangeal joint flexor strength and the anteroposterior average sway velocity of the center of gravity in one-leg standing with eyes closed following tDCS + FCE (r2 = 0.286; p = 0.057). The exploratory analysis also showed that compared with FCE alone, the sham stimulation did not induce any placebo effects during FCE.

Conclusion

Participating in 4 weeks of intervention using tDCS in combination with FCE effectively enhances toe flexor strength and foot–ankle sensory function.
A report on parent involvement in planning a randomised controlled trial in neonatology and lactation – insights for current and future research
Authors: Levene Ilana , Alderdice Fiona , McCleverty Beth , O’Brien Frances , Fewtrell Mary , Quigley Maria A.
Published: September 2022

Background

Patient and Public Involvement (PPI) is a rich and valuable part of the process of planning, designing, carrying out and disseminating research. It is important to communicate PPI findings in detail so that the contributions of those involved are fully utilised and disseminated. The extended and iterative PPI process used within a neonatal randomised controlled trial related to the expression of breastmilk after very preterm birth is reported here.

Methods

Seven iterative stages of PPI were used. Stage 1 was informal PPI using historical interaction with parents and publicly available resources. Stage 2 was an online questionnaire open to parents of premature babies and advertised via a charity collaborator. Stage 3 was partnership with a charity collaborator. Stage 4 was a set of online panels focusing on study design and documents. Stage 5 was an interactive exercise to modify the trial intervention. Stage 6 is the presence of PPI contributors on the trial steering committee. Stage 7 is a dissemination panel. At each stage attention was paid to the diversity of participants involved, with strategies to increase the involvement of parents from under-reached groups.

Results

Six hundred and seventy-five participants responded at Stage 2, six parents were involved at Stage 4 and 12 parents at Stage 5. PPI contributed to the choice of study question, outcomes and produced a set of questions for future research. PPI impacted on the study design, with specific emphasis on reducing participant distress related to lactation, and reducing the burden of being involved in research at a time of significant stress.

Conclusions

PPI had a far-reaching influence on this neonatal randomised controlled trial during the planning and design phase, which reinforces the importance of PPI at the earliest stages of the research cycle. The online questionnaire format elicited an unexpectedly deep and broad pool of transferable insights, which will have an impact on future research focus and design in the area of lactation and prematurity. Approaches to increasing PPI involvement from under-reached populations are important and can be successful despite resource constraints.
Phase I trial of hypofractionated chemoradiotherapy in the palliative management of esophageal and gastro-esophageal cancer
Authors: Sridharan Swetha , Day Fiona , Loh Jasmin , Lynam James , Smart Joanne , Holt Brandan , Mandaliya Hiren , Bonaventura Anthony , Kumar Mahesh , Martin Jarad
Published: September 2022

Background

Many patients with incurable esophageal cancer (ECa) present with dysphagia as their predominant symptom. Currently there is no consensus on how best to initially manage this scenario with multiple therapeutic options available. We aimed to assess the safety and efficacy of using hypofractionated radiotherapy given over a progressively shorter timeframe with concurrent carboplatin and paclitaxel in the management of patients with ECa and dysphagia.

Methods

In this phase I trial we enrolled patients with histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastro-esophageal junction with symptomatic dysphagia from local disease and not for curative treatment. Patients needed to be 18 years or older, have an ECOG performance status of 0–2 and be suitable to receive carboplatin and paclitaxel chemotherapy. Patients were placed in four progressively shorter radiation schedules culminating in 30 Gy in 10 fractions in a step wise manner, all with concurrent carboplatin AUC 2 and paclitaxel 50 mg/m2 chemotherapy delivered weekly with the radiation therapy. The primary endpoint was the development of the dose limiting toxicities (DLTs) esophageal perforation or febrile neutropenia. Secondary endpoints were relief of dysphagia, time to improvement of dysphagia, dysphagia progression free survival and overall survival.

Results

Eighteen patients were enrolled in the study between October 2014 and March 2019. There were no DLTs experienced during the trial. The most common grade 3 + acute toxicity experienced by patients were nausea and vomiting (both in 4/18 patients). The most common radiation specific acute toxicity experienced was esophagitis with 67% of patients experiencing grade 1–2 symptoms. All patients experienced improvement in dysphagia. The median time to dysphagia improvement was 3 weeks from the start of chemoradiotherapy (CTRT) (range 2–10 weeks). The median dysphagia free survival was 5.8 months with a median overall survival of 8.9 months.

Conclusion

Hypofractionated palliative CTRT with 30 Gy/10# of radiation therapy with concurrent weekly carboplatin and paclitaxel chemotherapy is well tolerated and provides a good response in improvement of dysphagia. Further studies need to be undertaken which provide both symptomatic improvement in the primary tumor but also control of the metastatic burden in these patients.

Clinical Trial Registration: This trial was prospectively registered with www.anzctr.org.au Identifier: ACTRN12614000821695.
The validity and reliability of the OneStep smartphone application under various gait conditions in healthy adults with feasibility in clinical practice
Authors: Christensen Jesse C. , Stanley Ethan C. , Oro Evan G. , Carlson Hunter B. , Naveh Yuval Y. , Shalita Rotem , Teitz Levi S.
Published: September 2022

Objective

Primary purpose of this study was to determine the validity and reliability of the OneStep smartphone application in healthy adults. Secondary purpose was to determine the feasibility of measuring gait dysfunction, limitation in spatiotemporal characteristics, longitudinally in patients following total hip or knee arthroplasty.

Methods

First objective, 20 healthy adults (mean age, 42.3 ± 19.7 years; 60% males; mean body mass index, 29.0 ± 5.2 kg/m2) underwent gait analysis under four gait conditions (self-selected gait speed, fixed gait speed at 0.8 m/s, fixed gait speed at 2.0 m/s and self-selected gait speed with dual task) for the validity and reliability of the smartphone to the motion laboratory. Reliability was determined by intraclass correlation coefficients. Validity was determined by Pearson correlations. Agreement was assessed by the Bland–Altman method. Second objective, 12 additional patients with total hip or knee arthroplasty (mean age, 58.7 ± 6.5 years; 58% males; mean body mass index, 28.9 ± 5.8 kg/m2) were measured at 2- and 10 weeks postoperatively. The smartphone application was used to evaluate change in gait dysfunction over time within the patients’ own environment using paired t test.

Results

The smartphone application demonstrated moderate-to-excellent intraclass correlation coefficients for reliability between-system (ICC range, 0.56–0.99), -limb (ICC range, 0.62–0.99) and -device (ICC range, 0.61–0.96) for gait analysis of healthy adults. Pearson correlations were low-to-very high between methods (r range, 0.45–0.99). Bland–Altman analysis revealed relative underestimation of spatiotemporal variables by the smartphone application compared to the motion system. For patients following total hip or knee arthroplasty, gait analysis using the OneStep application demonstrated significant improvement (p < 0.001, Cohen’s d > 0.95) in gait dysfunction between 2- and 10 weeks postoperatively.

Conclusion

The smartphone application can be a valid, reliable and feasible alternative to motion laboratories in evaluating deficits in gait dysfunction in various environments and clinical settings.
Microtubule-associated protein 1 A and tubby act independently in regulating the localization of stereocilin to the tips of inner ear hair cell stereocilia
Authors: Youn Song Yi , Min Hyehyun , Jeong Se Rok , Lee Jiahn , Moon Seok Jun , Bok Jinwoong , Kim Chul Hoon
Published: September 2022

Tubby mice exhibit hearing impairment due to the loss of stereocilin from the tip regions that connect the tallest stereocilia of the outer hair cells (OHCs) to the tectorial membrane. Stereocilin is an essential stereociliary protein in the OHCs, the mutation of which in humans causes autosomal recessive non-syndromic deafness. Map1a is a modifier of tubby hearing (moth1), and its wild-type allele, rather than the moth1 allele from the C57BL/6 J strain, restores stereocilin localization to the stereocilia and rescues the hearing impairment of tubby mice. The mechanism by which MAP1A accomplishes this is unclear, partly due to ambiguity regarding whether the tubby mutation is a true null. We therefore generated Tub-null (Tub−/−) mice by deleting exon 3 and found that they exhibit hearing impairment like that of tubby mice, suggesting the tubby mutation is a loss-of-function mutation with regard to hearing. When we crossed Tub−/− mice with AKR mice that have wild-type Map1a alleles, we found that wild-type MAP1A restores stereocilin localization to the tips of stereocilia and rescues hearing impairment. These data suggest MAP1A does not require interaction with tubby protein in maintaining stereocilin at the tips of stereocilia and that OHCs use two independent molecules—MAP1A and tubby—to doubly ensure proper stereocilin localization.
Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8+ T cell cytolytic killing of melanoma cells
Authors: Shaw Gary , Cavalcante Ludimila , Giles Francis J. , Taylor Alison
Published: September 2022

Background

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with multiple roles in tumour growth, cell invasion and metastasis. We have previously established GSK-3 as an upstream regulator of PD-1 gene expression in CD8 + T cells and demonstrated that GSK-3 inhibition is as effective as anti-PD-1 mAb blockade in controlling tumour growth. Elraglusib (9-ING-41) is a specific small-molecule inhibitor of GSK-3β with clinical activity in patients with advanced cancers, including a patient with refractory melanoma whose response provided the rationale for the current study.

Methods

The B16 melanoma mouse model was used to observe the effect of elraglusib on tumour growth either as a single agent or in combination (simultaneously and sequentially) with anti-PD-1 mAb treatment. B16 tumour cells were implanted in either the flank, brain or both locations, and Kaplan–Meier plots were used to depict survival and significance determined using log rank tests. Expression of the immune checkpoint molecules, TIGIT, LAG-3 and PD-1, was evaluated using flow cytometry alongside expression of the chemokine receptor, CXCR3. Further evaluation of PD-1 expression was determined through RT-qPCR and immunohistochemistry.

Results

We demonstrated that elraglusib has a suppressive effect against melanoma as a single agent and enhanced anti-PD-1 therapy. There was a synergistic effect when elraglusib was used in combination with anti-PD-1 mAb, and an even greater effect when used as sequential therapy. Suppression of tumour growth was associated with a reduced expression of immune checkpoint molecules, PD-1, TIGIT and LAG-3 with upregulation of CXCR3 expression.

Conclusions

These data highlight the potential of elraglusib as an immune-modulatory agent and demonstrate the benefit of a sequential approach with immune checkpoint inhibition followed by GSK-3β inhibition in melanoma and provide a rationale for clinical investigation of elraglusib combined with immune checkpoint inhibitory molecules, including those targeting PD-1, TIGIT and LAG-3. This has several potential implications for current immunotherapy regimes, including possibly reducing the intensity of anti-PD-1 mAb treatment needed for response in patients receiving elraglusib, especially given the benign adverse event profile of elraglusib observed to date. Based on these data, a clinical study of elraglusib, an anti-PD-1 mAb and chemotherapy is ongoing (NCT NCT05239182).
Effect of steroid treatment on the diagnostic yield of baseline 18f-fluorodeoxyglucose positron emission tomography in aggressive B cell lymphoma
Authors: Geiger Karyn Revital , Pasvolsky Oren , Berger Tamar , Raanani Pia , Shochat Tzippy , Gurion Ronit , Anati Tamer , Groshar David , Gafter-Gvili Anat , Bernstine Hanna
Published: September 2022

Aggressive B cell lymphoma often requires prompt steroid treatment, even before baseline 18f-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and definitive treatment, to alleviate symptoms or prevent organ damage. Since lymphoma is a steroid-sensitive malignancy, there are concerns that steroids might affect the results of FDG PET/CT and decrease its diagnostic yield. The aim of the current study was to evaluate the effect of steroids administered before baseline PET/CT on the maximum standardized uptake value (SUVmax) and additional PET/CT parameters. Retrospective review of the database in a tertiary medical center yielded 178 patients newly diagnosed with aggressive B cell lymphoma between January 2017 and May 2020 who had an available baseline FDG PET/CT scan. The cohort was divided into patients who received steroids before PET/CT (n = 47) and those who did not (n = 131), and the groups were compared for SUVmax and additional PET/CT parameters. The steroid-treated group had a higher disease stage and lactate dehydrogenase level compared to the steroid-naïve group, with a trend toward a higher international prognostic index. There was no significant between-group difference in SUVmax (P = 0.61). This finding remained consistent across steroid treatment durations and dosage regimens. Further evaluation revealed a significantly larger mean tumor volume and a trend toward a higher tumor metabolic burden in the steroid-treated group, yet no between-group difference in SUV mean or other PET/CT parameters. In this retrospective analysis of patients with aggressive B cell lymphoma, steroid prophase prior to baseline PET/CT did not decrease the diagnostic yield of the scan. However, further studies are required to fully appreciate the impact of steroids on PET CT parameters.
Host-specific probiotics feeding influence growth, gut microbiota, and fecal biomarkers in buffalo calves
Authors: Varada Vinay Venkatesh , Kumar Sachin , Chhotaray Supriya , Tyagi Amrish Kumar
Published: September 2022

The current study is aimed to evaluate the effect of host-specific probiotics on the gut microbiome, performance, and select fecal biomarkers of gut health in preruminant buffalo calves. Eight Murrah buffalo calves (3–5 days old; 32.52 ± 0.43 kg average body weight (BW)) were randomly allocated into two groups as follows; 1) Group I (n = 4) fed basal diet alone (CON); 2) Group II (n = 4) supplemented with a lyophilized probiotic formulation at a dose rate of 1 g/day/head (1 × 109 CFU/g) having Limosilactobacillus reuteri BF-E7 and Ligilactobacillus salivarius BF-17 along with basal diet (PF) for 30 days. Results revealed that final BW (kg), average daily gain (g/day), average dry matter intake (g/day), and structural growth measurements were significantly (P < 0.05) increased in the probiotics supplemented group (PF) compared to the control (CON). Fecal pH, fecal moisture, and fecal score were reduced (P < 0.05) in PF than in CON. Moreover, levels of fecal propionate, lactate, and ammonia altered positively in PF compared with CON. The relative abundance of Firmicutes tended to be higher (P = 0.10) in the probiotics fed group than CON. However, the relative abundance of Proteobacteria was significantly lower (P = 0.03) for calves fed probiotics on day 15. A trend was observed in Bacteroides (P = 0.07) and Lactobacillus (P = 0.08) abundances in the feces of the PF than in CON. Overall, it can be concluded that the administration of probiotic formulations significantly improved the performance and gut health of buffalo calves via modulating the gut microbiota composition.

Graphical Abstract
Metabolic framework of spontaneous and synthetic sourdough metacommunities to reveal microbial players responsible for resilience and performance
Authors: Calabrese Francesco Maria , Ameur Hana , Nikoloudaki Olga , Celano Giuseppe , Vacca Mirco , Junior Wilson JFLemos , Manzari Caterina , Vertè Fabienne , Di Cagno Raffaella , Pesole Graziano , De Angelis Maria , Gobbetti Marco
Published: September 2022

Background

In nature, microbial communities undergo changes in composition that threaten their resiliency. Here, we interrogated sourdough, a natural cereal-fermenting metacommunity, as a dynamic ecosystem in which players are subjected to continuous environmental and spatiotemporal stimuli.

Results

The inspection of spontaneous sourdough metagenomes and transcriptomes revealed dominant, subdominant and satellite players that are engaged in different functional pathways. The highest microbial richness was associated with the highest number of gene copies per pathway. Based on meta-omics data collected from 8 spontaneous sourdoughs and their identified microbiota, we de novo reconstructed a synthetic microbial community SDG. We also reconstructed SMC-SD43 from scratch using the microbial composition of its spontaneous sourdough equivalent for comparison. The KEGG number of dominant players in the SDG was not affected by depletion of a single player, whereas the subdominant and satellite species fluctuated, revealing unique contributions. Compared to SMC-SD43, SDG exhibited broader transcriptome redundancy. The invariant volatilome profile of SDG after in situ long-term back slopping revealed its stability. In contrast, SMC-SD43 lost many taxon members. Dominant, subdominant and satellite players together ensured gene and transcript redundancy.

Conclusions

Our study demonstrates how, by starting from spontaneous sourdoughs and reconstructing these communities synthetically, it was possible to unravel the metabolic contributions of individual players. For resilience and good performance, the sourdough metacommunity must include dominant, subdominant and satellite players, which together ensure gene and transcript redundancy. Overall, our study changes the paradigm and introduces theoretical foundations for directing food fermentations.
Global proteomic profiling of multiple organs of cats (Felis catus) and proteome-transcriptome correlation during acute Toxoplasma gondii infection
Authors: Nie Lan-Bi , Cong Wei , He Jun-Jun , Zheng Wen-Bin , Zhu Xing-Quan
Published: September 2022

Background

Toxoplasma gondii is a protozoan parasite which can infect almost all warm-blooded animals and humans. Understanding the differential expression of proteins and transcripts associated with T. gondii infection in its definitive host (cat) may improve our knowledge of how the parasite manipulates the molecular microenvironment of its definitive host. The aim of this study was to explore the global proteomic alterations in the major organs of cats during acute T. gondii infection.

Methods

iTRAQ-based quantitative proteomic profiling was performed on six organs (brain, liver, lung, spleen, heart and small intestine) of cats on day 7 post-infection by cysts of T. gondii PRU strain (Genotype II). Mascot software was used to conduct the student’s t-test. Proteins with P values < 0.05 and fold change > 1.2 or < 0.83 were considered as differentially expressed proteins (DEPs).

Results

A total of 32,657 proteins were identified in the six organs, including 2556 DEPs; of which 1325 were up-regulated and 1231 were down-regulated. The brain, liver, lung, spleen, heart and small intestine exhibited 125 DEPs, 463 DEPs, 255 DEPs, 283 DEPs, 855 DEPs and 575 DEPs, respectively. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of all proteins and DEPs in all organs showed that many proteins were enriched in binding, cell part, cell growth and death, signal transduction, translation, sorting and degradation, extracellular matrix remodeling, tryptophan catabolism, and immune system. Correlations between differentially expressed proteins and transcripts were detected in the liver (n = 19), small intestine (n = 17), heart (n = 9), lung (n = 9) and spleen (n = 3).

Conclusions

The present study identified 2556 DEPs in six cat tissues on day 7 after infection by T. gondii PRU strain, and functional enrichment analyses showed that these DEPs were associated with various cellular and metabolic processes. These findings provide a solid base for further in-depth investigation of the complex proteotranscriptomic reprogramming that mediates the dynamic interplays between T. gondii and the different feline tissues.
Assessing English language teachers’ understanding and practices of student-centered learning in Oman
Authors: Orabah Salim Said Bani , Bijani Houman , Ismail Seyed M.
Published: September 2022

Student-centered learning assessment (SCLA) constitutes a major component of current educational initiatives at the University of Technology and Applied Sciences (UTAS). However, little research has been conducted on English teachers’ understanding and practices of SCL assessment. Therefore, this study seeks to explore English teachers’ understanding and practices of SCL assessment at UTAS in Oman. The findings could provide information regarding teachers’ understanding and practices of SCLA. The findings may contribute to how English teachers define SCLA, what SCL-related activities they conduct, and how often these are conducted. Sixty-one teachers participated in the study with an average of 24 years of experience. A series of interviews and questions were used to elicit data from the participants. A questionnaire was used to explore teachers’ understanding of SCLA. Interviews were used in conjunction with the questionnaires to obtain more detailed information from the participants. The findings of this study showed that each of the English teachers has their definitions and understandings of SCLA; however, it was difficult to understand teachers’ definitions of SCLA due to the lack of a common definition for this term in the literature. Teachers should be encouraged to empower students by working in mixed groups on the basis that the advanced students each head up separate groups. The implication is to allow less able students to mimic and imitate their peers and improve their comprehension, pronunciation, and vocabulary in and out of the classroom. Future research could be enhanced by other stakeholders, such as students and administrators, involvement.
A Gaussian process regression accelerated multiscale model for conduction-radiation heat transfer in periodic composite materials with temperature-dependent thermal properties
Authors: Tong Zi-Xiang , Li Ming-Jia , Gu Zhaolin , Yan Jun-Jie , Tao Wen-Quan
Published: September 2022

Prediction of the coupled conduction-radiation heat transfer in composite materials with periodic structure is important in high-temperature applications of the materials. The temperature dependence of thermal properties complicates the problem. In this work, a multiscale model is proposed for the conduction-radiation heat transfer in periodic composite materials with temperature-dependent thermal properties. Homogenization analysis of the coupled conduction and radiative transfer equations is conducted, in which the temperature dependence of thermal properties is considered. Both the macroscopic homogenized equations and the local unit cell problems are derived. It is proved that the macroscopic average temperature can be used in the unit cell problems for the first-order corrections of the temperature and radiative intensity, and the calculations of effective thermal properties. The temperature dependence of thermal properties only influences the higher-order corrections. A multiscale numerical method is proposed based on the analysis. The Gaussian process (GP) regression is coupled into the multiscale algorithm to build a correlation between thermal properties and temperature for the macroscale iterations and prevent the repetitive solving of unit cell problems. The GP model is updated by additional solutions of unit cell problems during the iteration according to a variance threshold. Numerical simulations of conduction-radiation heat transfer in composite with isotropic and anisotropic periodic structures are used to validate the proposed multiscale model. It is found that the accuracy and efficiency of the multiscale method can be guaranteed by using a proper variance threshold for the GP model. The multiscale model can provide both the average temperature and radiative intensity fields and their detailed fluctuations due to the local structures.
Diagnostic utility of three Tesla diffusion tensor imaging in prostate cancer: correlation with Gleason score values
Authors: Abouelkheir Rasha Taha , Aboshamia Yasmin Ibrahim , Taman Saher Ebrahim
Published: September 2022

Background

Preoperative assessment of prostate cancer (PCa) aggressiveness is a prerequisite to provide specific management options. The Gleason score (GS) obtained from prostatic biopsy or surgery is crucial for the evaluation of PCa aggressiveness and personalized treatment planning. Diffusion tensor imaging (DTI) provides valuable information about microstructural properties of prostatic tissue. The most common prostate DTI measures are the fractional anisotropy (FA) and median diffusivity (MD) can give more information regarding the biophysical characteristics of prostate tissue. We aimed to explore the correlation of these DTI parameters with GS levels in PCa patients that can affect the management protocol of PCa.

Results

The computed area under curve (AUC) of the FA values used to differentiate cancer patients from control group was (0.90) with cutoff point to differentiate both groups were ≥ 0.245. The computed sensitivity, specificity, positive and negative predictive values were (84%, 80%, 95.5%, and 50%), respectively, with accuracy 83.3%. FA showed high positive correlation with Gleason score (p value < 0.001). Median diffusivity (MD) showed negative correlation with GS with statistically significant results (p value  = 0.013). PCa fiber bundles were dense, orderly arranged, without interruption in the low grade, and slightly disorganized in the intermediate group. However, in the high-grade group, the fiber bundles were interrupted, irregularly arranged, and absent at the site of cancerous foci.

Conclusions

Combined quantitative parameter values (FA and MD values) and parametric diagrams (FA and DTI maps) can be utilized to evaluate prostate cancer aggressiveness and prognosis, helping in the improvement of the management protocol of PCa patients.
Is Desmopressin Useful in the Evaluation of Cushing Syndrome?
Authors: Castinetti Frederic , Lacroix André
Published: September 2022

The desmopressin test was first described 30 years ago. Based on the differential secretagogue properties of desmopressin on adrenocorticotropin (ACTH) release between normal and corticotroph tumor cells, this test was intended to facilitate the diagnosis of Cushing syndrome (CS). The distinct expression of the various arginine vasopressin receptors between normal pituitary, corticotroph tumors, or neuroendocrine tumors cells secreting ACTH ectopically suggested that this test could facilitate the etiological diagnosis of ACTH-dependent CS. In this review, we analyze the merits and pitfalls of desmopressin use in the diagnostic procedures of CS. Desmopressin response is not able to completely differentiate the various etiologies of CS; its wider availability has allowed its use for inferior petrosal sinus sampling confirmation of a pituitary source of ACTH excess. In addition, desmopressin can be useful to demonstrate adequate corticotroph tumor resection when its stimulatory effect is lost following pituitary surgery of patients with Cushing disease. Desmopressin response can also be a marker of the risk of longer-term postoperative recurrence. However, this review also highlights the lack of consensual criteria of normal or abnormal response to desmopressin in its various uses and requirement for further research on its usefulness.