bluuebunny/crossref_metadata_2025 huggingface dataset:
White matter hyperintensities are a prominent feature of autosomal dominant Alzheimer’s disease that emerge prior to dementia
Authors: Schoemaker Dorothee , Zanon Zotin Maria Clara , Chen Kewei , Igwe Kay C. , Vila-Castelar Clara , Martinez Jairo , Baena Ana , Fox-Fuller Joshua T. , Lopera Francisco , Reiman Eric M. , Brickman Adam M. , Quiroz Yakeel T.
Published: June 2022

Background

To promote the development of effective therapies, there is an important need to characterize the full spectrum of neuropathological changes associated with Alzheimer’s disease. In line with this need, this study examined white matter abnormalities in individuals with early-onset autosomal dominant Alzheimer’s disease, in relation to age and symptom severity.

Methods

This is a cross-sectional analysis of data collected in members of a large kindred with a PSEN1 E280A mutation. Participants were recruited between September 2011 and July 2012 from the Colombian Alzheimer’s Prevention Initiative registry. The studied cohort comprised 50 participants aged between 20 and 55 years, including 20 cognitively unimpaired mutation carriers, 9 cognitively impaired mutation carriers, and 21 non-carriers. Participants completed an MRI, a lumbar puncture for cerebrospinal fluid collection, a florbetapir PET scan, and neurological and neuropsychological examinations. The volume of white matter hyperintensities (WMH) was compared between cognitively unimpaired carriers, cognitively impaired carriers, and non-carriers. Relationships between WMH, age, and cognitive performance were further examined in mutation carriers.

Results

The mean (SD) age of participants was 35.8 (9.6) years and 64% were women. Cardiovascular risk factors were uncommon and did not differ across groups. Cognitively impaired carriers [median, 6.37; interquartile range (IQR), 9.15] had an increased volume of WMH compared to both cognitively unimpaired carriers [median, 0.85; IQR, 0.79] and non-carriers [median, 1.07; IQR, 0.71]. In mutation carriers, the volume of WMH strongly correlated with cognition and age, with evidence for an accelerated rate of changes after the age of 43 years, 1 year earlier than the estimated median age of symptom onset. In multivariable regression models including cortical amyloid retention, superior parietal lobe cortical thickness, and cerebrospinal fluid phospho-tau, the volume of WMH was the only biomarker independently and significantly contributing to the total explained variance in cognitive performance.

Conclusions

The volume of WMH is increased among individuals with symptomatic autosomal-dominant Alzheimer’s disease, begins to increase prior to clinical symptom onset, and is an independent determinant of cognitive performance in this group. These findings suggest that WMH are a key component of autosomal-dominant Alzheimer’s disease that is closely related to the progression of clinical symptoms.
Dietary patterns and survival to 100 + years: an empty systematic review of cohort and case–control studies
Authors: Poulsen Winnie , Christensen Kaare , Dalgård Christine
Published: June 2022

Background

Centenarians are used as a model of healthy ageing and longevity. Diet is a factor known to affect mortality in middle aged adults and elderly. However, it is unknown whether diet has an impact on survival to 100 + years. The aims of this systematic review were to summarize the evidence on (i) the association between dietary patterns in late adult life and survival to 100 + years and (ii) the common characteristics across dietary patterns that are shown to be positively associated with survival to 100 + years.

Methods

We performed a systematic literature search in MEDLINE and EMBASE, and a hand search at four longevity projects homepages up to 4 June 2021. We searched for cohort and case–control studies investigating the association between dietary patterns and all-cause mortality among individuals aged ≥ 65 years at enrolment regardless of their health status and residence. Studies were excluded if follow-up was performed too soon to allow the population or a subgroup of it to have become 100 + years of age.

Results

Of 3,685 identified records 108 reports were retrieved and full text screened. No studies met our inclusion criteria, thus the review process resulted in no eligible studies found. Hence, no risk of bias assessment and no synthesis of data was performed.

Conclusions

No studies have investigated dietary patterns in late adult life in relation to survival to 100 + years of age. We have observed that as of June 2021 published cohort studies exist investigating all-cause mortality risk from different dietary patterns among the oldest old, but follow-up has been performed before the cohort could have reached 100 years of age. However, cohorts do exist where data on dietary habits in adult life has been collected decades ago and where follow-up in 2022 will allow the participants to have become 100 + years old.

Registration

The review protocol is published at University of Southern Denmark’s Research Portal (Poulsen et al. Dietary Patterns and Survival to 100 + Years: Protocol for a Systematic Review of cohort and case–control studies University of Southern Denmark's Research Portal: University of Southern Denmark, 2021) available at https://portal.findresearcher.sdu.dk/en/publications/kostm%C3%B8nstre-og-overlevelse-til-100-%C3%A5r-protokol-for-en-systematisk. We have specified aim (i) of our research question in this report compared to the protocol, by adding “late” to “adult life”.
Environmental and economic accounting for biomass energy in Ethiopia
Authors: Yalew Amsalu Woldie
Published: June 2022

Background

Energy consumption is inextricably linked with the economy and the environment. The interlinkages are particularly important in low-income countries such as Ethiopia where biomass fuels account for more than 85% of the total energy consumed. This paper aims to assess the energy and economic values, and environmental emissions of solid biomass fuels in Ethiopia.

Methods

The study considered four common solid biomass fuels (firewood, charcoal, crop residues, and cattle dung) in Ethiopia. The amount of biomass fuels during the Ethiopian fiscal year 2015/2016 was compiled from various data sources. Prices, net calorific values, and emission factors per mass of fuels were then used to calculate the economic, energy, and emission values of the solid biomass fuels.

Results

The study showed that, in 2015/2016, the consumption of the four solid biomass fuels contributed between 33,327 and 44,547 ktoe to the total energy consumption with an estimated economic value of 4.4–7.7% of the GDP at current market prices. The stationary combustion of the biomass fuels could result in 165–219 Mt of CO2eq emissions, whereas the fuelwood consumption could potentially impinge on the size or quality of 730 thousand ha of forest, woodlands, and shrublands.

Conclusions

The results suggest that the country should scale-up its policy measures aimed at increasing households’ access to modern energy sources and energy-efficient cooking stoves while at the same time strengthening its afforestation and reforestation activities.
A greater modified Mediterranean diet score is associated with lower insomnia score among adolescent girls: a cross-sectional study
Authors: Yaghtin Zahra , Beigrezaei Sara , Yuzbashian Emad , Ghayour-Mobarhan Majid , Khayyatzadeh Sayyed Saeid
Published: June 2022

Background

Previous studies has shown that a low quality diet is related to sleep disorders. A Mediterranean diet is considered to be a high quality diet and has been shown to have beneficial effects on overall health. Thus, the aim of our study was to investigate the association between adherence to Mediterranean dietary pattern and insomnia score among adolescent girls.

Methods

The data for 733 adolescent girls between 12–18 years old was assessed in this cross-sectional study. A 147 item-food frequency questionnaire was used to assess dietary intake. A modified model of Mediterranean diet score was calculated that ranged from 0–9 points. A validated version of Insomnia Severity Index questionnaire was used to assess insomnia. To explore the association between modified Mediterranean (mMED) diet score and insomnia, linear regression was conducted in crude and adjusted models (energy intake adjustmet in Model I, further adjustments were performed for physical activity, father’s and mother’s education in Model II and full adjusted model adjusted for age, body mass index percentiles, and abdominal obesity).

Results

A significant inverse association between mMED diet score and insomnia score was observed using a crude model (β = -0.091, 95% confidence interval (CI): -0.392 to -0.046); P-value = 0.013) and also after adjustment for confounding factors in Model I (β = -0.098, CI: -0.423 to -0.045; P = 0.015), Model II (β = -0.092, CI: -0.410 to -0.029; P-value = 0.024), Model III (β = -0.082, CI: -0.385 to -0.006); P = 0.044).

Conclusion

There was an inverse relationship between adherence to the mMED diet score and insomnia level among Iranian adolescent girls. Prospective studies are needed to confirm these results and clarify whether a causal relationship exists.
A case of refractory pneumothorax and contralateral atelectasis after thoracoscopic subtotal esophagectomy treated with independent lung ventilation
Authors: Hirai Natsuko , Konda Makiko , Naito Yusuke , Tanaka Nobuhiro , Egawa Junji , Kawaguchi Masahiko
Published: June 2022

Background

Independent lung ventilation (ILV) allows separate positive end-expiratory pressures (PEEP) and inspiratory pressures for each lung. However, only a few articles have reported ILV management for lungs affected by different pathologies.

Case presentation

A 56-year-old man underwent video-assisted thoracic surgery for esophageal cancer. The right lung was injured during surgery, causing a bronchopleural fistula and necessitating chest drainage. On the third day in the intensive care unit, the patient’s oxygenation worsened during pressure support with continuous positive airway pressure ventilation. ILV was initiated for right-sided severe pneumothorax and left-sided atelectasis and pneumonia. ILV was continued for 2 days, and the patient’s trachea was successfully extubated the following day.

Conclusion

Applying high-level PEEP to the one lung and minimizing the airway pressure on the other lung could be achieved using ILV, which might contribute to successful tracheal extubation.
Hazard ranking of wastewater sources in a highly polluted river in northern Taiwan by using positive matrix factorization with metal elements
Authors: Hsieh Pei-Yuan , Lin Huan-Chun , Wang Gen-Shuh , Hsu Yuan-Jeng , Chen Yi-Ju , Wang Tzu-Hui , Wang Ren-De , Kuo Chun-Yu , Wang Di-Wen , Liao Ho-Tang , Wu Chang-Fu
Published: June 2022

Improving water quality is a critical issue worldwide. However, the general parameters (i.e., temperature, pH, turbidity, total solids, fecal coliform, dissolved oxygen, biochemical oxygen demand, phosphates, and nitrates) used in water quality index estimations are unable to identify pollution from industrial wastewater. This study investigated pollution sources at a river pollution hotspot by using the positive matrix factorization (PMF) model. A two-phase sampling collection along a highly polluted river in northern Taiwan was designed. The sampling spots were distributed along the river in Phase I to monitor the spatial variation of river pollutants. A pollution hotspot was determined based on two indices, namely the summed concentrations of metal elements and a metal index (MI). In Phase II, the river water samples were collected from the hotspot twice daily over 30 consecutive days to monitor the temporal variation of river pollutants. Source profiles of metal elements were obtained during the monitoring period. The Phase II samples were then factorized using the PMF model. Factor profiles retrieved from the PMF model were further assigned to industrial categories through Pearson correlation coefficients and hierarchical classification. The results indicated that the main pollution source was bare printed circuit boards (BPCB), which contributed up to 92% of the copper in the pollution hotspot. In terms of MI apportionment of 11 metals related to health effects, BPCB contributed 91% of the MI in high pollution events. Overall, the MI apportionment provides linkages between pollution level and human health. This is an evidence for policymakers that the regulation of the effluents of BPCB is an effective means to controlling copper concentrations and thus improving water quality in the study area.
Digital spatial profiling to uncover biomarkers of immunotherapy outcomes in head and neck squamous cell carcinoma.
Authors: Gavrielatou Niki , Vathiotis Ioannis , Aung Thazin Nwe , Shafi Saba , Burela Sneha , Fernandez Aileen , Psyrri Amanda , Rimm David L.
Published: June 2022

6050

Background: Immunotherapy (ITx) has become the standard of care in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, response rate is limited to 13-18% of patients, underlining the need to identify mechanisms implicated in response or resistance. This study aims to uncover novel biomarkers of ITx outcomes in R/M HNSCC using digital spatial profiling (DSP) technology. Methods: Pre-treatment biopsy samples of 50 ITx-treated R/M HNSCC patients, constructed in the form of tissue microarray (YTMA496), were included in our discovery cohort. Cases underwent DSP with the Human Immuno-Oncology protein panel (NanoString Technologies), comprising 71 photocleavable oligonucleotide-labeled primary antibodies, used for target-protein quantification in 4 distinct molecularly defined compartments: tumor (CK+), leukocyte (CD45+), macrophage (CD68+) and immune stroma (CD45+/CD68+). All markers were explored for associations with progression-free (PFS) and overall survival (OS) using a univariate Cox regression model. Significant markers were validated using an alternative quantitative immunofluorescence method as well as in an independent validation cohort of 29 ITx-treated R/M HNSCC cases (YTMA523). Results: Univariate DSP data analysis revealed high beta2-microglobulin (B2M), LAG-3, CD25 and 4-1BB in tumor, high B2M, CD45 and CD4 in stroma, and low fibronectin in the macrophage compartment, as markers associated with improved PFS. Increased levels of B2M and CD25 in tumor and CD11c in stroma were also correlated with prolonged OS. Focusing on B2M, cases at the top tertile of tumor B2M expression were associated with improved PFS and OS [HR, 0.43; 95% confidence interval (CI), 0.21-0.9; p = 0.034 and HR, 0.41; 95% CI, 0.18-0.90; p = 0.047, respectively], by an orthogonal QIF method. Findings were replicated in our validation cohort for PFS [HR, 0.41; 95% CI, 0.19-0.93; p = 0.034] and showed a similar trend for OS [HR, 0.44; 95% CI, 0.19-1.0; p = 0.074]. B2M-high tumors also had significant enrichment with immune-cell markers (CD3, CD4, CD8, CD11c, CD68 and CD163) and increased immune checkpoint expression (PD-L1, ICOS, TIM-3, LAG-3, IDO1, B7-H3), predominantly in the tumor compartment. Conclusions: Our study indicates that intact, highly functional antigen presentation, sustained by high B2M expression in tumor, confers survival benefit in ITx treated R/M HNSCC patients, an effect driven by increased intra-tumoral immunogenicity.
TPF induction chemotherapy versus PF adjuvant chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicenter, randomized controlled, III trial.
Authors: Qianyong He
Published: June 2022

6069

Background: To investigate the efficacy and safety of the two modes of concurrent chemoradiotherapy combined with induction or adjuvant chronotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Methods: A total of 266 patients with locoregionally advanced NPC were enrolled from May 2018 to July 2021 and randomly divided into a test (n = 133) and a control (n = 133) group. In the test group, the docetaxel and cisplatin plus fluorouracil (TPF) regimen was used to induce chronological chemotherapy for 3 cycles (docetaxel 75mg / m2, D1, cisplatin 75mg / m2, d1-d5, fluorouracil 750mg / m2 / D, d1-d5) + 3 cycles of concurrent chemoradiotherapy (cisplatin 100mg / m2; The control group was treated with three cycles of concurrent chemoradiotherapy (cisplatin 100mg / m2) + cisplatin plus fluorouracil (PF) regimen with adjuvant schedule chemotherapy for three cycles (cisplatin 80mg / m2 on days d1-d5, fluorouracil 800mg / m2 / d on days d1-d5). In both groups, intensity-modulated radiation therapy was used with a total dose of 69.96 Gy to the primary tumor at T1 and T2, 72.6 Gy to the primary tumor at T3 and T4, and 69.96 Gy to the positive lymph nodes. Acute adverse effects and survival were compared between the two groups. Results: A median follow-up of 19 months, 129 patients in the test group and 124 in the control group were evaluable for efficacy and adverse effects.Compliance was 96.99% and 90.22%, respectively. The 2-year overall survival rates were 91.7% and 90.5%, and the 2-year progression free survival rates were 92.4% and 90.4% in the test and control groups, respectively, with no significant difference ( P > 0.05). The test group had a lower incidence of radiation mucositis, dry mouth, and dysphagia than the control group ( P < 0.05), whereas the test group had a higher incidence of leukopenia, neutropenia, hemoglobin loss, vomiting ( P < 0.05), decreased radiation dermatitis, platelets There were no significant differences in the categories of creatinine elevation and transaminase elevation (P > 0.05). Conclusions: The patients' compliance was good and the toxic effects such as radiation mucositis, dry mouth and dysphagia were reduced under the treatment mode in which the TPF induced chemotherapy combined with concurrent chemoradiotherapy.Although the toxic effects such as leukopenia, neutropenia, hemoglobin reduction and vomiting were increased, the efficacy was comparable with that of the PF in which the adjuvant schedule chemotherapy combined with concurrent chemoradiotherapy. Clinical trial information: NCT-03574324.
Phase III randomized control study evaluating adjuvant metronomic chemotherapy in locally advanced head and neck cancers post-radical chemoradiation (MACE-CTRT).
Authors: Chopade Sunil Ramdhan , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Bhattacharjee Atanu , Nawale Kavita Prakash , Banavali Shripad Dinanath , Prabhash Kumar , Mathrudev Vijayalakshmi
Published: June 2022

6073

Background: Locally advanced head and neck cancer treated with radical chemoradiation have unsatisfactory outcomes. Oral metronomic chemotherapy improves outcomes in comparison to maximum tolerated dose chemotherapy in the palliative setting. There is also limited evidence that it may do so in an adjuvant setting. Hence this randomised study was conducted. Methods: Patients of HN cancer with primary in oropharynx, larynx or hypopharynx, with PS 0-2 post radical chemoradiation with documented complete response were 1:1 randomised to either observation or oral metronomic adjuvant chemotherapy (MAC) for 18 months. MAC consisted of weekly oral methotrexate (15 mg/m2) and celecoxib (200 mg PO BD). The primary endpoint was OS and the overall sample size was 1038. The study had 3 planned interim analyses for efficacy and futility. Results: 137 patients were recruited and an interim analysis was done. The 3 year PFS in the observation arm was 67.1% (95% CI 53.8-77.3) and the same in the MAC arm was 62.5%(95%CI 49.4-73.1). The corresponding hazard ratio was 1.402 (95% CI 0.7393-2.66, P-value = 0.3). The 3 year OS in the observation arm was 77.3% (95% CI 64.4-86) and the same in the MAC arm was 64.1% (95%CI 51-74.5). The corresponding hazard ratio was 1.588 (95% CI 0.8734-2.886, P-value = 0.1). Any grade mucositis was seen in 30 patients (45.5%) in the MAC arm and 20 patients (28.2%) in the observation arm (P-value = 0.05). The rate of grade 3 or above mucositis was 7.6%(n = 5) in the MAC arm and 1.4%(n = 1) in the observation arm (P-value = 0.106). Conclusions: Both arms had similar OS. Hence observation post complete response post radical chemoradiation remains the standard of care. Clinical trial information: CTRI/2016/09/007315.
Outcomes by tobacco history in E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.
Authors: Mehra Ranee , Flamand Yael , Quon Harry , Garcia Joaquin J. , Weinstein Gregory S. , Duvvuri Umamaheswar , O'Malley Bert W. , Ozer Enver , Thomas Giovana R. , Koch Wayne , Gross Neil D. , Bell Richard Bryan , Saba Nabil F. , Lango Miriam , Bayon Rodrigo , Burtness Barbara , Ferris Robert L.
Published: June 2022

6077

Background: E3311 is a phase II randomized study which showed favorable outcomes among intermediate (INT) risk HPV+ OPC patients (pts) who underwent TOS followed by pathology-guided or adapted, deintensified adjuvant treatment. Among HPV+ pts treated with definitive chemoradiation, survival outcomes are worse among those who smoked > 10 pack years (pk-yrs). Methods: We retrospectively analyzed demographics, pathologic results, and efficacy outcomes from E3311 by smoking group (current (C) vs. former (F) and > 10 vs. ≤10 pk-yrs  the latter a pre-specified stratification factor for INT patients). Binary and categorical variables were compared using a chi-square test (or Fishers exact test for small sample sizes). Ordinal variables were compared using a Wilcoxon rank sum test. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using a log-rank test. Results: Among 359 evaluable pts, performance status (PS) was significantly worse for pts with > 10 pk-yrs vs. ≤10 pk-yrs (15.4% vs. 7.9% with PS of 1, p = 0.034). Primary site, margin status, histologic grade, stage, and extranodal extension were not significantly different between the groups of > 10 vs. ≤10 pk-yrs. Smoking status (F vs. C) was available for 182 pts with a history of smoking. Slightly more C vs. F smokers had tonsil as primary site (79.5% vs. 65.0%, p = 0.09). Positive margins were significantly more frequent among C smokers (10.3% vs. 2.1%; p = 0.029). Overall, there were no significant differences in PFS (p = 0.55) or OS (p = 0.94), comparing those with > 10 vs. ≤10 pk-yrs, or comparing C vs. F smokers (p = 0.76, p = 0.82, respectively). Similarly, no significant differences were observed within the treatment arms. (Table 1) Conclusions: In this analysis of smoking status in E3311, INT risk HPV+ OPC pts who are C smokers or have a history of > 10 pk-yrs had favorable 3-yr PFS and OS rates that were not significantly worse than those with < 10 pk-yrs history. This data represents the first treatment approach for HPV+ OPC in which outcomes were not influenced by smoking status. Clinical trial information: NCT01898494. [Table: see text]
Cabozantinib versus placebo in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who progressed after prior VEGFR-targeted therapy: Outcomes in prespecified subgroups based on histology subtypes.
Authors: Capdevila Jaume , Robinson Bruce , Sherman Steven I. , Jarząb Barbara , Lin Chia-Chi , Vaisman Fernanda , Hoff Ana , Hitre Erika , Bowles Daniel W. , Williamson Denise , Oliver Jennifer Wright , Keam Bhumsuk , Brose Marcia S.
Published: June 2022

6081

Background: DTC comprises multiple histology subtypes, the most common being papillary and follicular. Based on results of the phase 3 COSMIC-311 trial, the multikinase inhibitor cabozantinib was recently approved by FDA for the treatment of pts with RAIR DTC who progressed after prior VEGFR-targeted therapy (Brose et al. 2021). In an extended follow-up, median (m) progression-free survival (PFS) was 11 months (mo) for cabozantinib vs 1.9 mo for placebo (HR 0.22, 96% CI 0.15–0.32, P<.0001) in the intent-to-treat (ITT) population (Capdevila et al. ESMO 2021. Abstr LBA67). Here we present outcomes for prespecified subgroups based on the baseline histology subtypes of papillary and follicular thyroid cancers. Methods: Pts were randomized 2:1 to cabozantinib (60 mg QD) or placebo. Placebo pts could cross over to open-label cabozantinib upon disease progression per blinded independent radiology committee (BIRC). Primary endpoints were PFS (ITT) and objective response rate (ORR, first 100 randomized pts), per RECIST v1.1 assessed by BIRC. Results: After a median follow-up of 10.1 mo, 258 pts (170 cabozantinib, 88 placebo) had been randomized (data cutoff 8 Feb 2021); 150 pts (96 cabozantinib, 54 placebo) had papillary thyroid cancer (PTC) and 113 pts (78 cabozantinib, 35 placebo) had follicular thyroid cancer (FTC), with the PTC and FTC subgroups each including 5 pts with both PTC and FTC. Sixty-three pts (̃56%) within the FTC subgroup had Hurthle cell and poorly differentiated variants. mPFS was 9.2 mo for cabozantinib vs 1.9 mo for placebo in the PTC subgroup (HR 0.27, 95% CI 0.17–0.43) and 11.2 mo vs 2.6 mo in the FTC subgroup (HR 0.18, 95% CI 0.10–0.31). The mPFS was 11.1 mo for cabozantinib and 1.9 mo for placebo for pts with Hurthle cell and poorly differentiated variants (HR 0.12, 95% CI 0.05–0.27). The ORR was 15% for cabozantinib vs 0% for placebo in the PTC subgroup and 8% vs 0% in the FTC subgroup. Median duration of cabozantinib exposure was 5.5 mo for the PTC subgroup and 7.3 mo for FTC. Grade 3/4 treatment-emergent adverse events (TEAE) in the cabozantinib arm occurred in 59% of pts in the PTC subgroup and 68% of pts in the FTC subgroup; discontinuations due to TEAE occurred in 17% and 15% of pts, respectively. Conclusions: In the extended follow-up, cabozantinib maintained superior efficacy vs placebo irrespective of histology subtype, including the aggressive Hurthle cell and poorly differentiated variants. The moderately higher rates of grade 3/4 TEAE in the FTC vs the PTC subgroup could be attributed to the longer median duration of exposure of cabozantinib in the FTC subgroup. Clinical trial information: NCT03690388.
The prevalence and prognostic impact of mutations promoting chromatin remodelling dysregulation in non-resectable or recurrent/metastatic adenoid cystic carcinoma.
Authors: Rack Samuel , Feeney Laura , Mistry Hitesh , Betts Guy , Harrington Kevin Joseph , Metcalf Robert
Published: June 2022

6087

Background: Few effective drug therapies exist for patients with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC). Mutations in genes encoding chromatin remodelling proteins are described in almost 50% of ACC patients (pts). Novel drug therapies are being developed to target these pathways, and may have clinical utility in this sub-group. We sought to classify mutations in chromatin remodelling genes in ACC based on predicted pathogenicity and to determine the impact of chromatin remodelling dysregulation (CRD) on clinical outcomes. Methods: Matched clinical-genomic data from 269 pts with non-resectable or R/M ACC were included in this study. 130 pts were prospectively recruited to an ethically approved study. For these pts, DNA extracted from FFPE tissue was sequenced on a commercially available platform to detect point mutations, indels and copy number variation in 324 genes. In addition, clinical-genomic data from 139 ACC pts were collected from cBioPortal (MetTropism, Cell 2021) for analysis. Mutations were classified as pathogenic using COSMIC, ClinVar and OncoKB. Univariate survival analysis was performed to determine the impact of one or more mutations in chromatin remodelling genes on survival from first recurrence or metastasis. p values determined using Kaplan-Meier and log-rank. Results: In 269 pts with non-resectable or R/M ACC, mutations promoting CRD were identified in ARID1A (11%), CREBBP (5%), EP300 (5%), KMT2C (1%), KMT2D (5%), KDM6A (13%), and SETD2 (3%). CRD mutations were identified in 94/269 (35%) pts, with 27/269 (10%) having 2 or more CRD mutations. For patients in whom CRD mutations were present survival from recurrence was decreased (median OS 4.6 v 8.2 years, HR 1.65 (95% confidence interval (CI) 1.13-2.40), p = 0.01). Analysis of each individual CRD gene identified that association with decreased survival from recurrence was significant for mutations in KDM6A (n = 35; median OS 4.2 vs 6.5 years; HR 2.01 (95% CI 1.25-3.22); p = 0.004), CREBBP (n = 11; median OS 4.2 vs 5.9 years; HR 2.97 (95% CI 1.20-7.38); p = 0.019) and SETD2 (n = 7; median OS 3.7 vs 5.9; HR 2.47 (95% CI 1.002-6.09); p = 0.042). Previous studies have identified NOTCH pathway activation and TP53 loss-of-function as prognostic. In a secondary analysis of pts without NOTCH activation and/or TP53 mutations (n = 202), OS from recurrence was decreased in those with CRD mutations (n = 58 median OS 5.7 vs 9.2 years, HR 1.5 (CI 95% 0.95-2.55), p = 0.07). Conclusions: We have identified a novel prognostic group of ACC pts characterised by mutations promoting CRD, which may have potential therapeutic options. Alterations in EP300/CREBBP/ARID1A may provide a rationale for treatment with CREBBP/EP300 inhibitors currently in clinical development. Significant co-occurrence with NOTCH gain of function may provide a rationale for future combination studies.
Phase I study of AIC100 in relapsed and/or refractory advanced thyroid cancer and anaplastic thyroid cancer.
Authors: Hsu Jing Mei , von Hofe Eric , Hsu Yen-Michael , Shieh Jae-Hung , Chaekal Ok-Kyong , Guarneri Danielle , Fahey Thomas J. , Ivanidze Jana , Puc Janusz , Du Karrie , You Ashlee , Scognamiglio Theresa , Vasovic Ljiljana , Cushing Melissa , Jin Moonsoo , Van Besien Koen
Published: June 2022

6093

Background: ICAM-1 is a cell surface glycoprotein that is typically expressed on endothelial cells and immune cells and a ligand for LFA-1 integrin. It is also overexpressed in several malignancies, in particular anaplastic and advanced thyroid cancer. We designed an affinity tuned ICAM-1-directed CAR T cell (micromolar affinity) that preferentially binds overexpressed ICAM-1 on tumor cells and spares normal cells. The CAR T cells also express somatostatin receptor 2 (SSTR2), which allows tracking of CAR T cells in vivo via DOTATATE PET/CT scan. Murine studies showed excellent responses in ICAM-1 expressing thyroid cancer without significant toxicities. We are conducting a first-in-human phase 1 clinical trial to evaluate the feasibility, safety and preliminary efficacy of ICAM-1 in patients with relapsed/refractory thyroid cancer or anaplastic thyroid cancer who are BRAF wild-type, or BRAF mutated after failure of BRAF specific therapy (NCT04420754). Methods: This is a dose-escalation study with modified toxicity probability interval design and cohorts of 3 Patients. Patients receive a single dose of 1x 107 (Cohort 1), 1 x 108 (Cohort 2) or 5 x 108 (Cohort 3) ICAM-1 CAR T cells after FLU/CY lymphodepleting (LD) chemotherapy. Additional CAR T infusion is allowed if patients achieve partial response or stable disease. Whole-body Fluorodeoxyglucose (FDG) and DOTATATE PET/CT is used to stage tumor and track CAR T cells in vivo, respectively. Results: All ICAM-1 CAR T infusion products met target transduction efficiency. Two patients with progressive anaplastic thyroid cancer received ICAM-1 CAR T therapy at dose-level I. Evaluation of CAR T cellular kinetics demonstrated transient peripheral blood CAR T cell expansion. One patient developed grade 1 cytokine release syndrome (CRS) with fever. Several tumor lesions from this patient showed DOTATATE avidity, indicating CAR T homing to the tumor, concomitant with decrease in FDG avidity, suggesting biological activity at ̃2 weeks post CAR T infusion. DOTATATE avidity at 2 weeks post CAR T infusion also appeared to match that of CAR T abundance in the blood. Updated results on additional patients and cohorts will be presented. Conclusions: Adoptive cellular therapy with ICAM-1 directed CAR T is safe and feasible at dose level 1 in patients with anaplastic thyroid cancer. DOTATATE PET allows visualization of expansion and homing of SSTR2 expressing CAR T cells, while concomitant FDG PET permits correlation with biological activity. Clinical trial information: NCT04420754.
The Effects of Diabetes and Glycemic Control on Cancer Outcomes in Individuals With Metastatic Breast Cancer
Authors: Cheung Yee-Ming M , Hughes Melissa , Harrod Julia , Files Janet , Kirkner Greg , Buckley Lauren , Lin Nancy U , Tolaney Sara M , McDonnell Marie E , Min Le
Published: June 2022

Background

It is unclear whether diabetes and glycemic control affects the outcomes of breast cancer, especially among those with metastatic disease. This study aims to determine the impact of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer (MBC).

Methods

Patients with a diagnosis of MBC between 2010 and 2021 were identified using the MBC database at 2 academic institutions. We evaluated the effects of diabetes and glycemic control on overall survival (OS) and time to next treatment (TTNT).

Results

We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes (matched for age, sex, ethnicity, and receptor subtype). OS at 5 years [diabetes: 54% (95% CI 47-62%) vs controls: 56% (95% CI 49-63%), P = 0.65] and TTNT at 1 year [diabetes: 43% (95% CI 36-50%) vs controls: 44% (95% CI 36-51%), P = 0.33] were similar between groups. A subgroup analysis comparing those with good glycemic control and those with poor glycemic control among patients with specific receptor subtype profiles showed no differences in OS at 5 years or TTNT at 1 year. In an 8-year landmark subgroup analysis, there was worse OS among individuals with diabetes compared to controls, and OS was found to be better among those with good glycemic control compared to those with poor control.

Conclusions

Diabetes was not associated with increased mortality in individuals with MBC at 5 years. However, diabetes and hyperglycemia were associated with worse OS among a cohort of longer-term survivors. These findings suggest that individualized diabetes and glycemic goals should be considered in patients with MBC.
Crip/Mad Archive Dances
Authors: Kuppers Petra
Published: June 2022

Petra Kuppers reflects on her work in the crip/mad archive, which explores the work of mad, queer, and disabled predecessors in the fields of dance and performance. Kuppers consider how her personal relationship to therapeutic dance has changed (particularly therapeutic practices led by nondisabled artists such as Anne Wilson Wangh) and the importance of movement and embodiment in Kuppers’s own work—including a close description of ritual dance reenactments she conducted alongside her archival work at Lincoln Center in New York in 2021.
When Choices Are Mistakes
Authors: Nielsen Kirby , Rehbeck John
Published: June 2022

Using a laboratory experiment, we identify whether decision-makers consider it a mistake to violate canonical choice axioms. To do this, we incentivize subjects to report axioms they want their decisions to satisfy. Then, subjects make lottery choices which might conflict with their axiom preferences. In instances of conflict, we give subjects the opportunity to re-evaluate their decisions. We find that many individuals want to follow canonical axioms and revise their choices to be consistent with the axioms. In a shorter online experiment, we show correlations of mistakes with response times and measures of cognition. (JEL C91, D12, D44, D91)
Factor Market Failures and the Adoption of Irrigation in Rwanda
Authors: Jones Maria , Kondylis Florence , Loeser John , Magruder Jeremy
Published: June 2022

Factor market failures can limit adoption of profitable technologies. We leverage a plot-level spatial regression discontinuity design in the context of irrigation use by farmers provided free access to water. Using irrigation boosts profits by 43–62 percent. Yet, farmers only irrigate 30 percent of plots because of labor costs. We demonstrate inefficient irrigation use, by showing farmers irrigating one plot reduce their irrigation use on other plots. This inefficiency is largest for smaller households and wealthier households, suggesting labor market frictions constrain use of irrigation. (JEL D24, O13, Q12, Q15, Q16)
Evaluation of the compatibility of C2, C3, and C4 fractal dimension values with hand-wrist and cervical vertebra maturation methods in determining skeletal maturation
Authors: Pamukcu Umut , Ispir Nebiha Gozde , Akay Gulsun , Karadag Atas Ozge , Gungor Kahraman , Toraman Meryem
Published: June 2022

Objectives:

To examine the correlation between the fractal dimension (FD) values of cervical vertebrae (C2, C3, and C4) and hand-wrist maturation (HWM) and cervical vertebra maturation (CVM) methods. In addition, the correlation between the pubertal growth spurt (PGS) and FD values was examined.

Methods:

The lateral cephalometric and hand-wrist radiographs of 120 subjects (61 females and 59 males) aged 8–18 years with a mean age of 13 years, were evaluated retrospectively. The CVM stages were determined in accordance with Hassel-Farman’s modification of Lamparski criteria. The HWM stages were determined in accordance with Björk and Grave-Brown criteria. Both HWM and CVM stages were divided into two according to PGS. Fractal analysis of cervical vertebrae was performed according to the White-Rudolph method. The relationships between HWM stages, CVM stages and other variables were evaluated by Spearman’s rank-order correlation coefficient. The relationships between FD values, chronological age, and divided stages were evaluated by the Pearson correlation coefficient. The Mann–Whitney U test was used to compare the FD values of two divided stages.

Results:

There were positive and statistically significant positive correlations between chronological age and both HWM and CVM stages. There was a positive and statistically significant correlation between CVM and HWM stages. In females and total, there were negative and statistically significant correlations between C4 FD values and divided HWM stages, and the differences between C4 FD values of divided HWM stages were also statistically significant. In total, there was a negative and statistically significant correlation between C4 FD values and divided CVM stages, and the difference between C4 FD values of divided CVM stages was also statistically significant.

Conclusion:

The negative correlations found between C4 FD values and divided HWM and CVM stages suggest the fractal analysis of cervical vertebrae, especially of C4, may be used as an objective tool for evaluating the PGS.
Scoliosis incidence and treatment methods
Authors: Ionițe Cătălin , Rotariu Mariana , Osean Vasile , Mitran Cristina , Condurache Iustina
Published: June 2022

Scoliosis is defined as a three-dimensional deformity of the spine that is of particular interest to the lateral curvature of the spine. Various types of treatment approaches have been recommended for patients with scoliosis. The aim of this study was to provide an up-to-date review of scoliosis, focusing on issues such as its incidence and treatment methods. The ISI-Thomson Web Of Science International Virtual Library was accessed for this review. The search criteria selected were 'title', 'abstract' and 'keywords'. In the ISI Thomson Web of Science virtual library platforms, the keywords in the articles search were "scoliosis incidence" and "scoliosis treatment". Over the years, different therapeutic strategies have been addressed for patients with scoliosis, they differ depending on the type of scoliosis, the patient's age and the available therapeutic means. Keywords: Scoliosis, Incidence, Physical Treatment;
Effectiveness of a peanut ball device during labour on maternal and neonatal outcomes: protocol for a randomised controlled trial
Authors: Kamath Pratibha , Pai Muralidhar , Shenoy Revathi , Karkada Sushmitha , D’souza Sonia , Noronha Judith
Published: June 2022

Frequent positional changes and movements during labour is one of the recommendations by the World Health Organization (WHO) to prevent prolonged labour, thereby avoiding cesarean sections. However, labour induction, continuous fetal monitoring in supine position and immobilising the women during labour are standard practices in most private hospitals. To combat these problems and to implement WHO recommendations, the peanut ball is an effective device through which frequent positional changes will be achieved without disrupting the labour procedures. The current study aims to evaluate the effectiveness of the peanut ball device during labour on maternal and neonatal outcomes and assess the stress response induced by labour in terms of maternal and neonatal cortisol in low-risk primigravid women. The study is a prospective, block randomised controlled trial with parallel arms. A total of 768 study participants will be randomised to the peanut-ball group (intervention) and standard care group (control). The intervention group will receive different peanut ball positions during labour at or after 4 cm of cervical dilatation. The primary outcomes of the study are maternal outcome that includes measurement of duration of the active and the second stage of labour, stress level as measured by serum cortisol level at 3–4 cm and at 10 cm of cervical dilatation, mode of delivery, perception of pain, behavioural response during the active stage of labour and neonatal outcomes, which includes the pattern of fetal heart rate, APGAR score, birth injuries, and umbilical serum and salivary cortisol level. The collected data will be compared between the intervention and control groups. 

Trial Registration: This research is registered under the CTRI (Clinical Trials Registry of India) (CTRI/2019/08/020802) (21/8/2019).
Tourette syndrome research highlights from 2021
Authors: Hartmann Andreas , Andrén Per , Atkinson-Clement Cyril , Czernecki Virginie , Delorme Cécile , Debes Nanette Marinette , Szejko Natalia , Ueda Keisuke , Black Kevin
Published: June 2022

We summarize selected research reports from 2021 relevant to Tourette syndrome that the authors consider most important or interesting. The authors welcome article suggestions and thoughtful feedback from readers.
The role and importance of emotions in the situation of distance teaching-learning process during the pandemic of COVID-19
Authors: Dyundik Yuliya , Shishmareva Tatiana
Published: June 2022

People all over the world continue to adjust to the new reality we had to face with the COVID-19 pandemic outbreak, when some social restrictions have been enforced. These restrictions severely limited face-to-face interactions and included in particular work-from-home and study-from-home. The shift from face-to-face lessons to entirely virtual model resulted in implementing distance education technologies, students and teachers had to get used to using different online platforms, which caused many emotional reactions in the education process mostly because of omission of high-quality interaction and increase of individual work. Students, as well as teachers, had to adapt to these changes in a short period of time, which turned out to be extremely stressful for all members of studying-teaching process. The purpose of this practice-based paper is to explore how teachers and students got adjusted to the situation and present the authors’ ideas on some problems they came across when working distantly during the period of Covid-19 pandemic. Emotions seem to be a pivotal point in education, so the authors mostly concentrate on general overview of connection between emotions on the whole and the emotional state of both parties of communication – teachers and students – and their role in successful teaching-learning process.
Peculiarities of states of psychological well-being of internal affairs officers with different levels of service loyalty
Authors: Sarsenova Asel
Published: June 2022

The article considers the problem of interrelation of service loyalty and substantiates the position that loyalty is not only a significant factor in ensuring the effectiveness of professional activity, but also an indicator of subjective well-being. The aim of the paper is to establish psychological peculiarities of psychological well-being experience by internal affairs officers with different levels of loyalty. The hypothesis of the research was the assumption that there is a reliably significant relationship between the indicators of loyalty and psychological well-being of internal affairs officers. The research sample consisted of active employees of territorial bodies of internal affairs (n=200, male - 153, female - 47, the length of service of respondents was 10.6 years and age - 33 years). Research methods: loyalty measurement technique by S.S. Baranskaya, Organizational Loyalty Scale by J. Meyer, N. Allen, Psychological Well-being Scale by K. Riff (adaptation by T.D. Shevelenkov, P.P. Fesenko), method «Motive realization possibility» by V.I. Dominyak. The study revealed common and different values in the indicators of groups of employees with high and low levels of loyalty on the scales of «Autonomy» and «Personal Growth» (p≤0.05). The correlation analysis revealed reliable positive relations of psychological well-being and emotional, professional loyalty, and negative relations of well-being and disloyal behavior in the group of employees with high loyalty level. In the group of employees with a low level of loyalty, the values of well-being correlate positively with the values of professional loyalty and negatively with the values of continued and normative loyalty.
Project Management in the Field of Culture and Art
Authors: Sapelkina M.
Published: June 2022

Project management practices in various spheres of human activity have received a considerable interest over the past few decades on the territory of the Russian Federation. In the modern world, considering an increase in the role of culture in socio-economic transformations, project management can be viewed as the most effective way to create the combination of traditional and innovative principles and the necessary measures to address various problems. However, little is known about the vital processes of project management in the arts sphere and the obstacles encountered in its implementation. The proposed study generalizes the experience of project application and seeks to define a methodology for strengthening cultural policy with the project-based approach.

The relevance of the findings for governmental and non-governmental employees and the potential implications for future research will be discussed.
„Bogurodzica” i aktorzy interpretacji: edytorzy oraz edycje
Authors: Obremski Krzysztof
Published: June 2022

Publikacja intencjonalnie jest bądź przynajmniej powinna stać się dopełnieniem innej, mianowicie Pawła Bohuszewicza Aktorów interpretacji („Teksty Drugie” 2021, nr 2, s. 101–117). Pierwszoplanowa w tamtym tekście archaiczna część Bogurodzicy szczególnie wyraziście unaocznia, że ważni aktorzy interpretacji to także edytorzy oraz edycje. „Pieśń ojców” jest tekstem wyjątkowym w tym, że dowodzi, jak koniecznym punktem wyjścia literaturoznawczych działań pozostają przyjmowane wybory edycji.
Edytor: jednak aktor, nie reżyser interpretacji. Odpowiedź Krzysztofowi Obremskiemu
Authors: Bohuszewicz Paweł
Published: June 2022

Odpowiedź na polemikę Krzysztofa Obremskiego zawartą w artykule „Bogurodzica” i aktorzy interpretacji: edytorzy oraz edycje.
Osobliwość lemowych kalk – o korespondencji Stanisława Lema w dobie PRL-u
Authors: Bukowski Filip
Published: June 2022

Rec.: W. Orliński, Lem w PRL-u, czyli Nieco prawdy w zwiększonej objętości: na podstawie korespondencji StanisławaLema, przekłady listów z języka niemieckiego E. Zarych, z języka angielskiego M. Płaza, Wydawnictwo Literackie, Kraków 2021.