bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population
Authors: Ji Pei , Chang Jiang , Wei Xiaoyu , Song Xueyao , Yuan Hua , Gong Linnan , Li Yuancheng , Ding Dongsheng , Zhang Erbao , Yan Caiwang , Zhu Meng , Miao Xiaoping , Wu Chen , Jin Guangfu , Hu Zhibin , Shen Hongbing , Ma Hongxia 
Published: March 2021

BackgroundSquamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified.MethodsAn association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN.ResultsWe first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10−7 for rs2517611 at 6p22.1, p=1.76×10−9 for rs2524182 at 6p21.33 and p=2.17×10−10 for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1 to the promoter of TCF19. In addition, experiments revealed that the inhibition of TCF19 may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN.ConclusionThese findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that TCF19 may function as a putative susceptibility gene for SCCHN.
Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study
Authors: Nuovo Sara , Micalizzi Alessia , Romaniello Romina , Arrigoni Filippo , Ginevrino Monia , Casella Antonella , Serpieri Valentina , D'Arrigo Stefano , Briguglio Marilena , Salerno Grazia Gabriella , Rossato Sara , Sartori Stefano , Leuzzi Vincenzo , Battini Roberta , Ben-Zeev Bruria , Graziano Claudio , Mirabelli Badenier Marisol , Brankovic Vesna , Nardocci Nardo , Spiegel Ronen , Petković Ramadža Danijela , Vento Giovanni , Marti Itxaso , Simonati Alessandro , Dipresa Savina , Freri Elena , Mazza Tommaso , Bassi Maria Teresa , Bosco Luca , Travaglini Lorena , Zanni Ginevra , Bertini Enrico Silvio , Vanacore Nicola , Borgatti Renato , Valente Enza Maria 
Published: March 2021

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in TSEN54 and pathogenic variants in EXOSC3 accounted for 18% and 9% of cases, respectively. VLDLR, TOE1 and RARS2 were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with TSEN54 and lower motor neuron signs with EXOSC3. When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for EXOSC3.ConclusionCASK represents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between CASK and TSEN54-associated disorders.
γδ T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival
Authors: Gherardin Nicholas A. , Waldeck Kelly , Caneborg Alex , Martelotto Luciano G. , Balachander Shiva , Zethoven Magnus , Petrone Pasquale M. , Pattison Andrew , Wilmott James S. , Quiñones-Parra Sergio M. , Rossello Fernando , Posner Atara , Wong Annie , Weppler Alison M. , Shannon Kerwin F. , Hong Angela , Ferguson Peter M. , Jakrot Valerie , Raleigh Jeanette , Hatzimihalis Athena , Neeson Paul J. , Deleso Paolo , Johnston Meredith , Chua Margaret , Becker Juergen C. , Sandhu Shahneen , McArthur Grant A. , Gill Anthony J. , Scolyer Richard A. , Hicks Rodney J. , Godfrey Dale I. , Tothill Richard W. 
Published: March 2021

Abstract
Merkel cell carcinomas (MCC) are immunogenic skin cancers associated with viral infection or UV mutagenesis. To study T-cell infiltrates in MCC, we analyzed 58 MCC lesions from 39 patients using multiplex-IHC/immunofluorescence (m-IHC/IF). CD4+ or CD8+ T cells comprised the majority of infiltrating T lymphocytes in most tumors. However, almost half of the tumors harbored prominent CD4/CD8 double-negative (DN) T-cell infiltrates (&gt;20% DN T cells), and in 12% of cases, DN T cells represented the majority of T cells. Flow cytometric analysis of single-cell suspensions from fresh tumors identified DN T cells as predominantly Vδ2− γδ T cells. In the context of γδ T–cell inflammation, these cells expressed PD-1 and LAG3, which is consistent with a suppressed or exhausted phenotype, and CD103, which indicates tissue residency. Furthermore, single-cell RNA sequencing (scRNA-seq) identified a transcriptional profile of γδ T cells suggestive of proinflammatory potential. T-cell receptor (TCR) analysis confirmed clonal expansion of Vδ1 and Vδ3 clonotypes, and functional studies using cloned γδ TCRs demonstrated restriction of these for CD1c and MR1 antigen-presenting molecules. On the basis of a 13-gene γδ T–cell signature derived from scRNA-seq analysis, gene-set enrichment on bulk RNA-seq data showed a positive correlation between enrichment scores and DN T-cell infiltrates. An improved disease-specific survival was evident for patients with high enrichment scores, and complete responses to anti–PD-1/PD-L1 treatment were observed in three of four cases with high enrichment scores. Thus, γδ T–cell infiltration may serve as a prognostic biomarker and should be explored for therapeutic interventions.
See related Spotlight on p. 600
Transient Depletion of CD4+ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer
Authors: Aoki Hiroyasu , Ueha Satoshi , Shichino Shigeyuki , Ogiwara Haru , Shitara Kohei , Shimomura Manami , Suzuki Toshihiro , Nakatsura Tetsuya , Yamashita Makiko , Kitano Shigehisa , Kuroda Sakiko , Wakabayashi Masashi , Kurachi Makoto , Ito Satoru , Doi Toshihiko , Matsushima Kouji 
Published: March 2021

AbstractAntibody-mediated transient depletion of CD4+ cells enhances the expansion of tumor-reactive CD8+ T cells and exhibits robust antitumor effects in preclinical and clinical studies. To investigate the clonal T-cell responses following transient CD4+ cell depletion in patients with cancer, we conducted a temporal analysis of the T-cell receptor (TCR) repertoire in the first-in-human clinical trial of IT1208, a defucosylated humanized monoclonal anti-CD4. Transient depletion of CD4+ cells promoted replacement of T-cell clones among CD4+ and CD8+ T cells in the blood. This replacement of the TCR repertoire was associated with the extent of CD4+ T-cell depletion and an increase in CD8+ T-cell count in the blood. Next, we focused on T-cell clones overlapping between the blood and tumor in order to track tumor-associated T-cell clones in the blood. The total frequency of blood–tumor overlapping clones tended to increase in patients receiving a depleting dose of anti-CD4, which was accompanied by the replacement of overlapping clones. The greater expansion of CD8+ overlapping clones was commonly observed in the patients who achieved tumor shrinkage. These results suggested that the clonal replacement of the TCR repertoire induced by transient CD4+ cell depletion was accompanied by the expansion of tumor-reactive T-cell clones that mediated antitumor responses. Our findings propose beneficial remodeling of the TCR repertoire following transient CD4+ cell depletion and provide novel insight into the antitumor effects of monoclonal anti-CD4 treatment in patients with cancer.See related Spotlight on p. 601
Sleep Timing May Predict Congestive Heart Failure: A Community‐Based Cohort Study
Authors: Yan Bin , Li Ruohan , Li Jiamei , Jin Xuting , Gao Fan , Gao Ya , Ren Jiajia , Zhang Jingjing , Wang Xiaochuang , Wang Gang 
Published: March 2021

Background
Previous studies have suggested that sleep timing is associated with cardiovascular risk factors. However, there is no evidence on the relationship between sleep timing and congestive heart failure (CHF). We aimed to examine this relationship in this study.

Methods and Results

We recruited 4765 participants (2207 men; mean age, 63.6±11.0 years) from the SHHS (Sleep Heart Health Study) database in this multicenter prospective cohort study. Follow‐up was conducted until the first CHF diagnosis between baseline and the final censoring date. Sleep timing (bedtimes and wake‐up times on weekdays and weekends) was based on a self‐reported questionnaire. Cox proportional hazard models were constructed to investigate the association between sleep timing and CHF. During the mean follow‐up period of 11 years, 519 cases of CHF (10.9%) were reported. The multivariable Cox proportional hazards models revealed that participants with weekday bedtimes >12:00
am
(hazard ratio [HR], 1.56; 95% CI, 1.15–2.11;
P
=0.004) and from 11:01
pm
to 12:00
am
(HR, 1.25; 95% CI, 1.00–1.56;
P
=0.047) had an increased risk of CHF compared with those with bedtimes from 10:01
pm
to 11:00
pm
. After stratified analysis, the association was intensified in participants with a self‐reported sleep duration of 6 to 8 hours. Furthermore, wake‐up times >8:00
am
on weekdays (HR, 1.53; 95% CI, 1.07–2.17;
P
=0.018) were associated with a higher risk of incident CHF than wake‐up times ≤6:00
am
.

Conclusions

Delayed bedtimes (>11:00
pm
) and wake‐up times (>8:00
am
) on weekdays were associated with an increased risk of CHF.
Comparing Knowledge-Intensive and Data-Intensive Models for English Resource Semantic Parsing
Authors: Cao Junjie , Lin Zi , Sun Weiwei , Wan Xiaojun 
Published: March 2021

AbstractIn this work, we present a phenomenon-oriented comparative analysis of the two dominant approaches in English Resource Semantic (ERS) parsing: classic, knowledge-intensive and neural, data-intensive models. To reflect state-of-the-art neural NLP technologies, a factorization-based parser is introduced that can produce Elementary Dependency Structures much more accurately than previous data-driven parsers. We conduct a suite of tests for different linguistic phenomena to analyze the grammatical competence of different parsers, where we show that, despite comparable performance overall, knowledge- and data-intensive models produce different types of errors, in a way that can be explained by their theoretical properties. This analysis is beneficial to in-depth evaluation of several representative parsing techniques and leads to new directions for parser development.
Outcomes of Surgical and Nonsurgical Treatment for Colorectal Cancer in Nonagenarian Patients
Authors: Jeon Youngbae , Han Kyoung-Won , Lee Won-Suk , Baek Jeong-Heum 
Published: March 2021

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.
Dose–response relationships of psilocybin-induced subjective experiences in humans
Authors: Hirschfeld Tim , Schmidt Timo T 
Published: March 2021

Background: Psilocybin is the psychoactive component in Psilocybe mushrooms (‘magic mushrooms’). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies. Aim: Establishing dose–response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups. Method: We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose–response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale. Results: Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose. Conclusion: Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.
‘N-Angle’: Clinical Indicator for Predictable Insertion of Ramal Bone Screws
Authors: Patni Vivek J , Kolge Neeraj E , Pednekar Madhura J 
Published: March 2021

Introduction: The primary concern in the placement of ramal bone screws is the blind nature of the procedure, as there is a thick, mobile layer of soft tissue over the bone; also, the ramus is not a uniplanar structure but is swerving like a propeller blade. The purpose of this study was to evaluate the possibility of establishing clinical guidelines based on visible dental and soft-tissue landmarks for safe, reliable, and accurate insertion of ramal bone screws. Aims and Objectives: Our primary objective was to evaluate the angle formed between the appropriate direction of ramal-implant placement and the line tangential to the buccal surfaces of the first and second permanent molars. Our secondary objective was to evaluate the average distance of the neurovascular bundle from the tip of the bone screw. Materials and Methods: We obtained 80 cone beam computed tomography (CBCT) samples, marked reference lines and points on selected axial and coronal sections, and evaluated the following parameters using the software’s linear- and angular-measurement device: the angle between the appropriate direction of ramal bone screw placement and the line tangential to the buccal surfaces of the first and second permanent molars; and the proximity of the bone screw to the neurovascular bundle. Results: The angle between the constructed line of insertion and the occlusal line, as evaluated from our study, was 19.04 (SD ± 6.89) degrees. The proximity of the neurovascular bundle from the screw is 7.1773 (SD ± 1.73988) mm. Conclusion: We can conclude that ramal bone screws can be placed with a comfortable margin of safety.
Discovering the secrets of leadership success: Comparing commercial and academic preoccupations
Authors: Maskor Mazlan , Steffens Niklas K , Peters Kim , Haslam S Alexander 
Published: March 2021

Having access to the “secrets” of leadership promises to be immensely valuable to those wishing to lead. But what are these “secrets”? In this study, we examined the types of non-academic theorizing (communicated as leadership “secrets”) that writings for a general audience convey. A content analysis of 131 commercial books on leadership “secrets” revealed seven major “secrets” that pertained to (1) knowledge and learning, (2) habits, behaviors, and practices, (3) handling failure, challenges, and struggle, (4) personal inspiration, drive, and motivation, (5) team, group, and organizational strategy, (6) choices and decisions, and (7) communication skills. Intriguingly, the prevalence of leadership “secrets” varied in a cyclical pattern across time such that some “secrets” lost prominence in one period only to reemerge in another. We also observed a considerable degree of correspondence between the foci of topics in these commercial outlets and the foci of academic publications. JEL Classification: J24, O15, M12
Aseptic Revision and Reoperation Risks After Meniscectomy at the Time of Anterior Cruciate Ligament Reconstruction
Authors: Young Edmond P. , Chan Priscilla H. , Prentice Heather A. , Amar Karun , Hurvitz Andrew P. , Khan Najeeb A. 
Published: March 2021

Background: An intact meniscus is considered a secondary stabilizer of the knee after anterior cruciate ligament reconstruction (ACLR). While loss of the meniscus can increase forces on the anterior cruciate ligament graft after reconstruction, it is unclear whether this increased loading affects the success of the graft after ACLR. Purpose: To identify the risk of subsequent knee surgery when meniscectomy, either partial or total, is performed at the time of index ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: We conducted a matched cohort study using data from the Kaiser Permanente Anterior Cruciate Ligament Reconstruction Registry. Patients were identified who had a primary ACLR performed between January 1, 2005 and December 31, 2016, with up to 12 years of follow-up. The study sample comprised patients with ACLR who had a lateral meniscectomy (n = 2581), medial meniscectomy (n = 1802), or lateral and medial meniscectomies (n = 666). For each meniscectomy subgroup, patients with ACLR alone were matched to patients with a meniscectomy on a number of patient and procedure characteristics. After the application of matching, Cox proportional hazards regression was used to evaluate the risk of aseptic revision, while competing risks regression was used to evaluate the risk of cause-specific ipsilateral reoperation between meniscectomy and ACLR alone. Analysis was performed for each meniscectomy subgroup. Results: After the application of matching, we failed to observe a difference in aseptic revision risk for patients with ACLR and a meniscectomy—lateral (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02), medial (HR, 0.95; 95% CI, 0.70-1.29), or both (HR, 1.25; 95% CI, 0.77-2.04)—as compared with ACLR alone. When compared with patients who had ACLR alone, patients with a lateral meniscectomy had a higher risk for subsequent lateral meniscectomy (HR, 1.89; 95% CI, 1.18-3.02; P = .008), and those with a medial meniscectomy had a lower risk for manipulation under anesthesia (HR, 0.13; 95% CI, 0.02-0.92; P = .041). Conclusion: No difference in aseptic revision risk was observed for patients undergoing primary ACLR between groups with and without meniscectomy at the time of index surgery. Partial lateral meniscectomy at the time of index ACLR did associate with a higher risk of subsequent lateral meniscectomy.
Eligibility and patient barriers to peritoneal dialysis in patients with advanced chronic kidney disease
Authors: Abdulkarim Saleem , Shah Jasmit , Twahir Ahmed , Sokwala Ahmed P 
Published: March 2021

Introduction: The burden of chronic kidney disease (CKD) is increasing in Kenya and is a significant cause of morbidity and mortality. While definitive treatment is renal transplantation, many patients require kidney replacement therapy with haemodialysis (HD) or peritoneal dialysis (PD). The predominant modality utilized in Kenya is currently HD. There is a need to explore why PD remains underutilized and whether patient factors may be contributory to barriers that limit the uptake of PD. Methods: This was a descriptive cross-sectional study where patients with advanced CKD were assessed by a multidisciplinary team for PD eligibility using a standardized tool. Contraindications and barriers to the modality were recorded as was the presence or absence of support for the provision of PD. Demographic and clinical data were recorded using a standardized questionnaire. The impact of support on PD eligibility was determined. Results: We found that 68.9% patients were eligible for PD. Surgery-related abdominal scarring was the most common contraindication. Barriers to PD were identified in 45.9% and physical barriers were more common than cognitive barriers. Presence of support was associated with a significant increase in PD eligibility ( p < 0.001). Conclusion: The rate of eligibility for PD in this study was similar to that found in other populations. Surgical-related factors were the most commonly identified contraindication. Physical and cognitive barriers were commonly identified and may be overcome by the presence of support for PD.