bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insula network connectivity mediates the association between childhood maltreatment and depressive symptoms in major depressive disorder patients
Authors: He Cancan , Fan Dandan , Liu Xinyi , Wang Qing , Zhang Haisan , Zhang Hongxing , Zhang Zhijun , Xie Chunming 
Published: March 2022

AbstractChildhood maltreatment (CM) is a major risk factor for developing the major depressive disorder (MDD), however, the neurobiological mechanism linking CM and MDD remains unclear. We recruited 34 healthy controls (HCs) and 44 MDD patients to complete the childhood maltreatment experience assessment with Childhood Trauma Questionnaire (CTQ) and resting-state fMRI scan. Multivariate linear regression analysis was employed to identify the main effects of CM and depressive symptoms total and subfactors scores on bilateral anterior and posterior insula functional connectivity (IFC) networks, respectively. Mediation analysis was performed to investigate whether IFC strength mediates the association between CM and depressive symptoms. MDD patients showed significantly decreased connectivity in the dorsal medial prefrontal cortex and increased connectivity in the medial frontal gyrus in the bipartite IFC networks, compared to HCs. The main effects of CM and depressive symptoms showed a large discrepancy on the anterior and posterior IFC networks, which primarily located in the frontal-limbic system. Further, conjunction analysis identified the overlapping regions linking CM and depressive symptoms were mainly implicated in self-regulation and cognitive processing circuits. More important, these IFC strengths could mediate the association between different types of CM, especially for childhood abuse and childhood neglect, and depressive symptoms in those overlapping regions. We demonstrated that early exposure to CM may increase the vulnerability to depression by influencing brain’s self-regulating and cognitive processing circuitry. These findings provide new insight into the understanding of pathological mechanism underlying CM-induced depressive symptoms.
Structural basis for mismatch surveillance by CRISPR–Cas9
Authors: Bravo Jack P. K. , Liu Mu-Sen , Hibshman Grace N. , Dangerfield Tyler L. , Jung Kyungseok , McCool Ryan S. , Johnson Kenneth A. , Taylor David W. 
Published: March 2022

AbstractCRISPR–Cas9 as a programmable genome editing tool is hindered by off-target DNA cleavage1–4, and the underlying mechanisms by which Cas9 recognizes mismatches are poorly understood5–7. Although Cas9 variants with greater discrimination against mismatches have been designed8–10, these suffer from substantially reduced rates of on-target DNA cleavage5,11. Here we used kinetics-guided cryo-electron microscopy to determine the structure of Cas9 at different stages of mismatch cleavage. We observed a distinct, linear conformation of the guide RNA–DNA duplex formed in the presence of mismatches, which prevents Cas9 activation. Although the canonical kinked guide RNA–DNA duplex conformation facilitates DNA cleavage, we observe that substrates that contain mismatches distal to the protospacer adjacent motif are stabilized by reorganization of a loop in the RuvC domain. Mutagenesis of mismatch-stabilizing residues reduces off-target DNA cleavage but maintains rapid on-target DNA cleavage. By targeting regions that are exclusively involved in mismatch tolerance, we provide a proof of concept for the design of next-generation high-fidelity Cas9 variants.
Metabolites of soil microorganisms modulate amyloid β production in Alzheimer’s neurons
Authors: Kondo Takayuki , Yamamoto Tsuyoshi , Okayama Kaoru , Narumi Hideki , Inoue Haruhisa 
Published: March 2022

AbstractMicrobial flora is investigated to be related with neuropathological conditions in Alzheimer’s disease (AD), and is attracting attention as a drug discovery resource. However, the relevance between the soil microbiota and the pathological condition has not been fully clarified due to the difficulty in isolation culture and the component complexity. In this study, we established a library of secondly metabolites produced in microorganism to investigate the potential effect of microorganisms on the production of amyloid β (Aβ), one of the most representative pathogens of AD. We conducted a library screening to quantify Aβ and neuronal toxicity by using cortical neurons from human induced pluripotent stem cells (iPSCs) of AD patients after adding secondary metabolites. Screening results and following assessment of dose-dependency identified Verrucarin A, produced in Myrothecium spp., showed 80% decrease in Aβ production. Furthermore, addition of Mer-A2026A, produced in Streptomyces pactum, showed increase in Aβ42/40 ratio at the low concentration, and decrease in Aβ production at the higher concentration. As a result, established library and iPSC-based phenotyping assay clarified a direct link between Aβ production and soil microorganisms. These results suggest that Aβ-microorganism interaction may provide insight into the AD pathophysiology with potential therapeutics.
Improved spin–orbit torque induced magnetization switching efficiency by helium ion irradiation
Authors: An Suhyeok , Baek Eunchong , Kim Jin-A , Lee Ki-Seung , You Chun-Yeol 
Published: March 2022

AbstractIncreasing the efficiency of spin–orbit torque (SOT) is of great interest in spintronics devices because of its application to the non-volatile magnetic random access memory and in-logic memory devices. Accordingly, there are several studies to alter the magnetic properties and reduce the SOT switching current with helium ion irradiation, but previous researches are focused on its phenomenological changes only. Here, the authors observe the reduction of switching current and analyze its origins. The analyzed major reasons are improved spin Hall angle represented as the changed resistivity of heavy metal layer and the reduction of surface anisotropy energy at interface between heavy metal and ferromagnet. It is confirmed that almost linear relation between changed SHA and Pt resistivity by helium ion irradiation, which is attributed because of the increase in the scattering sources induced by structural distortion during ion penetration. From the calculated power consumption ratio based on the derived parameter, the requiring power decreases according to the degree of ion irradiation. Our results show that helium ion penetration induced layer and interfacial disturbance affects SOT induced magnetization switching current reduction and may provide possibility about helium ion irradiation based superior SOT device engineering.
Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis
Authors: Saijo Sayaka , Ohno Mikiko , Iwasaki Hirotaka , Matsuda Shintaro , Nishi Kiyoto , Hiraoka Yoshinori , Ide Natsuki , Kimura Takeshi , Nishi Eiichiro 
Published: March 2022

AbstractBrown adipose tissue (BAT) dissipates chemical energy as heat through uncoupling protein 1 (UCP1). The induction of mitochondrial reactive oxygen species (ROS) in BAT was recently identified as a mechanism that supports UCP1-dependent thermogenesis. We previously demonstrated that nardilysin (NRDC) plays critical roles in body temperature homeostasis. Global NRDC-deficient (Nrdc–/–) mice show hypothermia due to a lower set point for body temperature, whereas BAT thermogenesis at room temperature (RT) is enhanced mainly to compensate for poor thermal insulation. To examine the primary role of NRDC in BAT thermogenesis, we generated adipocyte-specific NRDC-deficient (Adipo-KO) mice by mating Nrdc floxed (Nrdcflox/flox) mice with adiponectin-Cre mice. Adipo-KO mice showed hyperthermia at both RT and thermoneutrality. They were also more cold-tolerant than Nrdcflox/flox mice. However, UCP1 mRNA levels were significantly lower in Adipo-KO BAT at RT, thermoneutrality, and 4 °C, whereas no significant differences were observed in UCP1 protein levels at RT and 4 °C. We examined the protein stability of UCP1 using the cycloheximide chase assay and found that NRDC negatively regulated its stability via the ubiquitin–proteasome pathway. NRDC may be also involved in ROS-mediated in vivo thermogenesis because the inhibitory effects of N-acetyl cysteine, an ROS scavenger, on β3 agonist-induced thermogenesis were stronger in Adipo-KO mice. Collectively, the present results demonstrate that NRDC in BAT controls adaptive thermogenesis and body temperature homeostasis possibly via the regulation of UCP1 protein stability and ROS levels.
TRPA1s act as chemosensors but not as cold sensors or mechanosensors to trigger the swallowing reflex in rats
Authors: Hossain Mohammad Zakir , Ando Hiroshi , Unno Shumpei , Kitagawa Junichi 
Published: March 2022

AbstractWe examined the role of TRPA1s in triggering the swallowing reflex. TRPA1s predominantly localized on thin nerve fibers and fibroblast-like cells in swallowing-related regions and on small to medium-sized superior laryngeal nerve-afferents in the nodose–petrosal–jugular ganglionic complex. Topical application of a TRPA1 agonist, allyl isothiocyanate (AITC), dose-dependently triggered swallowing reflexes. Prior topical application of a TRPA1 antagonist significantly attenuated the AITC-induced reflexes. Application of cold AITC (4 °C) very briefly reduced the on-site temperature to < 17 °C (temperature at which TRPA1s can be activated), but had no effect on triggering of the reflex. By contrast, reducing the on-site temperature to < 17 °C for a longer time by continuous flow of cold AITC or by application of iced AITC paradoxically delayed/prevented the triggering of AITC-induced reflexes. Prior application of the TRPA1 antagonist had no effect on the threshold for the punctate mechanical stimuli-induced reflex or the number of low-force or high-force continuous mechanical pressure stimuli-induced reflexes. TRPA1s are functional and act as chemosensors, but not as cold sensors or mechanosensors, for triggering of the swallowing reflex. A brief cold stimulus has no effect on triggering of the reflex. However, a longer cold stimulus delays/prevents triggering of the reflex because of cold anesthesia.
Sirolimus-eluting cobalt–chrome alloy stent suppresses stent-induced tissue hyperplasia in a porcine Eustachian tube model
Authors: Kang Jeon Min , Kim Song Hee , Choi Yeon Joo , Park Yubeen , Ryu Dae Sung , Kang Woo Seok , Park Jung-Hoon , Park Hong Ju 
Published: March 2022

AbstractVarious preclinical studies with developed Eustachian tube (ET) stents are in progress but have not yet been clinically applied. ET stent is limited by stent-induced tissue hyperplasia in preclinical studies. The effectiveness of sirolimus-eluting cobalt–chrome alloy stent (SES) in suppressing stent-induced tissue hyperplasia after stent placement in the porcine ET model was investigated. Six pigs were divided into two groups (i.e., the control and the SES groups) with three pigs for each group. The control group received an uncoated cobalt–chrome alloy stent (n = 6), and the SES group received a sirolimus-eluting cobalt–chrome alloy stent (n = 6). All groups were sacrificed 4 weeks after stent placement. Stent placement was successful in all ETs without procedure-related complications. None of the stents was able to keep its round shape as original, and mucus accumulation was observed inside and around the stent in both groups. On histologic analysis, the tissue hyperplasia area and the thickness of submucosal fibrosis were significantly lower in the SES group than in the control group. SES seems to be effective in suppressing stent-induced tissue hyperplasia in porcine ET. However, further investigation was required to verify the optimal stent materials and antiproliferative drugs.
Teacher Educational Decision Making for Children With Specific Language Impairment
Authors: Girolamo Teresa M. , Rice Mabel L. , Selin Claire M. , Wang Chien J. 
Published: March 2022

Purpose:
Children with specific language impairment (SLI) are underidentified, despite a robust literature on their language abilities and a clinical grammar marker. Adlof and Hogan (2019) call for school systems to assess oral language and provide supports through response to intervention (RTI), with the aim of identifying and supporting children with SLI and other language impairments. However, it is unknown how teachers make educational decisions for children with SLI.

Method:

A web-based survey was distributed to public school teachers nationwide (
N
= 304). In this observational study, teachers read six vignettes featuring profiles of children systematically varying in the linguistic characteristics relevant to SLI (e.g., difficulty with verb tense) and responded to items on the educational decisions that they would make in the absence of workplace constraints.

Results:
Teachers were likely to identify that the children in the vignettes needed language for classroom success and to indicate that they would provide in-class intervention. However, teachers were unlikely to recommend speech-language pathology services. These outcomes were mostly consistent across all child characteristics and teacher characteristics.

Conclusions:
Findings show that teachers were sensitive to the language-based needs of children with SLI and elected to provide in-class intervention. Future work is needed to understand how workplace characteristics, including opportunities for interprofessional collaboration, and the heterogeneity of children with SLI, inform teacher educational decision making.
A high‐precision adaptive blind estimation method for chaotic time series
Authors: Liu Fang , Cheng Mowen , Feng Yongxin 
Published: February 2022

AbstractTo improve the estimation accuracy of chaotic time series and reduce the computational complexity, a high‐precision adaptive blind estimation method is proposed. By introducing the pre‐treatment method, the adaptive identification model is established, and the linear estimation equation is derived. Through the organic combination of the model and the least square mechanism, the complexity of the model is limited. When changing the type and length of the sequence, the parameters can be changed adaptively, so as to construct the corresponding trajectory equation and realize the blind estimation of chaotic time series. The analysis and experimental results show that the estimation accuracy of this method can reach 10–16 order of magnitude.
Liebe Leserinnen und Leser,
Authors: Dengler Reinhard , Zierz Stephan 
Published: March 2022

Liebe Leserinnen und Leser,die diagnostischen Möglichkeiten bei Myopathien und anderen
neuromuskulären Erkrankungen sind in den vergangenen Jahrzehnten deutlich
mehr geworden und haben vielfach auch zu einem besseren Verständnis
einzelner neuromuskulären Erkrankungen geführt.
Clinicoepidemiological Profile and Treatment Outcomes in Children with Retinoblastoma: Experience from a Cancer Care Center in Northeast India
Authors: Hazarika Munlima , Kumar Gaurav , Saikia Bhargab Jyoti , Sarangi Satya Sadhan , Roy Partha Sarathi , Bhattacharjee Kasturi , Barman Manabjyoti 
Published: February 2022

Background Retinoblastoma (RB) is the most common primary intraocular malignancy in children. We sought to provide a comprehensive assessment of epidemiological profile and treatment outcomes of children with RB.
Methods In this retrospective study, we analyzed 189 children diagnosed with RB at our center between 2004 and 2017. Survival was analyzed with the Kaplan–Meier method and log-rank test.
Results Median age at presentation was 14 months with male: female ratio 1.2:1. Mean duration between onset of symptoms and presentation was 49 days (standard deviation ± 79). Most common presenting symptom was white pupillary reflex in 60% of children. Family history of RB and other cancers was found in one (0.5%) and seven (4%) children, respectively. Primary mode of diagnosis and staging was ocular ultrasonography (bone scan) in 87% of patients. Computed tomographic scan and magnetic resonance imaging were done in 124 (66%) and 30 (16%) patients, respectively. International staging system grade E disease was found in 144 (76%), extraocular disease in 55 (29%), bilateral disease in 49 (26%), and trilateral disease in 3 (1.5%) children. Out of 189 children with RB, 33 (18%) refused treatment and 156 children received treatment (24 children [15%] abandoned treatment midway and 132 [85%] completed treatment). One hundred children (64%) received systemic therapy as neoadjuvant or adjuvant chemotherapy and 20 (13%) received local therapy. Eyeball and vision salvage rate with chemotherapy were 20 (13%) and 9 (6%), respectively. Cryotherapy was the most common modality of local treatment used in 11 (55%) children. Five-year survival for patients who received treatment was 76% (median survival not reached). In the treatment refusal group, median survival was 9 months.
Conclusion In developing countries, RB is mostly detected in advanced stages resulting in poor outcomes. Increased awareness and accessibility to dedicated centers for treating childhood malignancy can lead to early diagnosis, better prognosis, and increased vision salvage.
Compliance of Radiotherapy Treatment at a Tertiary Cancer Center in India—A Clinical Audit
Authors: Khanna Nehal R. , Kumar Anuj , Kataki Kaushik , Sehra Nishtha , Laskar Sarbani Ghosh , Mummudi Naveen , Gupta Tejpal , Tibdewal Anil , Pathak Rima , Wadasadawala Tabassum , Krishnatry Rahul , Chopra Supriya , Goda Jayant Sastri , Chatterjee Abhishek , Budrukkar Ashwini , Gurram Lavanya , Engineer Reena , Murthy Vedang , Swain Monali , Laskar Siddhartha , Sarin Rajiv , Agarwal Jai Prakash 
Published: February 2022

Abstract
Introduction Noncompliance to planned radiotherapy (RT) treatment is associated with inferior outcomes and also serves as an indicator of quality of care offered to the patients. Identification of the rate of noncompliance and its causative factors can help us develop an insight toward implementing mitigation measures thereby improving the quality of treatment.
Objective To ascertain the incidence of noncompliance and the factors affecting the same in patients offered RT appointments.
Materials and Methods We retrospectively reviewed the records of patients from January 1, 2019, to December 31, 2019, who were noncompliant (defaulted RT simulation or defaulted initiation of RT or defaulted planned RT during the course of RT but excluding planned/unplanned treatment breaks or early conclusions prescribed by the treating radiation oncologist) for the planned RT treatment.
Results Of the 8,607 appointments (7,699 external beam RT and 908 brachytherapy) given to the patients attending the radiation oncology outpatient department in the year 2019, a total of 197 (2.28%) patients were found to be noncomplaint. Ninety-seven patients defaulted RT simulation (49.2%), 53 defaulted RT starting (26.9%), and 47 defaulted while on RT (23.9%). Half of these had either head–neck (29.9%) or gynecological (20.8%) malignancies. Patients with breast cancers had the least noncompliance rates (0.02%). The cause for noncompliance was ascertained in 135 patients (68.5%). The common causes of noncompliance were the desire to continue treatment closer to home (21.5%) followed by logistic (17%), lack of confidence in the curative potential of the planned therapy (17%), and financial reasons (11.8%). Patients with head–neck and gynecological malignancies were more often with advanced staged disease and were planned multimodal treatment protocols. The majority of the 23 patients who defaulted palliative RT were planned for fractionated treatments (73.9%).
Conclusion The incidence of noncompliance in patients planned for RT in our institute can be considered optimum. Appropriate counseling of patients at the time of scheduling appointment, upfront identification of patients at high risk of noncompliance, and assisting patients with financial and logistic challenges are imperative to ensure adherence to planned treatment schedule.
Prognostic Significance of HE4 Tissue Expression in Serous Epithelial Ovarian Carcinoma
Authors: Sethi Ankita , Kumar Lalit , Mathur Sandeep , Mahey Reeta , Kachhawa Garima , Bhatla Neerja 
Published: February 2022

Background Human Epididymis protein 4 (HE4) is expressed in ovarian cancer. Preoperative serum testing is still not widely available. This pilot study aimed to investigate the magnitude of expression of HE4 in tissue sections of serous epithelial ovarian carcinoma, its correlation with clinical outcome, and the feasibility of HE4 immunohistochemistry as a prognostic marker.
Materials and Method In this ambispective study, immunohistochemistry (IHC) was used to evaluate tissue sections of ovarian serous epithelial carcinoma at primary cytoreductive surgery. On HE4 immunohistochemistry (IHC), the magnitude of HE4 expression was assessed categorically as high or low HE4 expression and semiquantitatively by the H-score, and correlated with clinical outcome in terms of survival status, progression-free survival, and overall survival.
Results Of 32 cases, most (n = 31, 96.8%) were positive for HE4 IHC. The mean age was 49 ± 8.2 years; 29 (90.6%) patients were in FIGO stage IIIC; 25 (78.9%) had ≥1cm residual disease after surgery; 31 (96.8%) received adjuvant chemotherapy, either 3-weekly (n = 25, 81.2%) or dose-dense weekly (n = 6, 18.8%) regimen. The majority (n = 31, 96.8%) had a high-grade tumor, of whom 19 (59.4%) had high HE4 expression and 13(40.6%) patients had H-score in the range of 5 to 8. The mean H-score was 6.97 ± 3.61 (range 0 to 12). The overall survival of the study population at 64 months was 36.65% (95% CI: 8.59–66.34), with median overall survival of 59 months. A new scoring system was developed combining categorical HE4 expression and serum CA-125 levels; the combination of HE4 expression with postoperative CA-125 levels was found to be the best prognostic marker for overall survival (p = 0.05). A composite score of 2 identified patients with poor progression-free survival (HR 4.64, p = 0.039) and overall survival (HR 5.45, p = 0.05).
Conclusion The new composite scoring system using HE4 IHC with postoperative serum CA-125 levels offers an extremely useful option for prognosticating patients with serous epithelial ovarian carcinoma than serum CA-125 alone. This is useful where preoperative records are not available to the treating clinician.
Performance on a Spanish Picture-Identification Task Using a Multimedia Format
Authors: McCullough June Antablin , Wilson Richard H. 
Published: March 2022

AbstractAn option for estimating the word-recognition performance of patients who do not speak English as a first language involves using auditory materials, presented in the patient’s native language, in conjunction with a closed-set response mode incorporating pictures or written words. The advantage of this auditory/visual paradigm is that the audiologist is not required to know the foreign language and is therefore not required to judge the accuracy of an oral response to speech stimuli in a foreign language. Spanish auditory/visual materials, known as the Spanish Picture-Identification Task, were developed to be used in a computer- driven multimedia administration and scoring format. Performance data, both in open- (word-recognition) and closed-set (word-identification) response modes, were established for the Spanish Picture-Identification Task using subjects whose first language was Spanish. The results from the open-set paradigm indicate that the Spanish Picture-Identification Task word lists are essentially equivalent to conventional Spanish and English materials used for word recognition. Findings from the closed-set conditions indicate that the Spanish Picture- Identification Task materials are appropriate for estimating the word-identification abilities of Spanish-speaking adult listeners.