bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical and perioperative treatment strategy for resectable esophagogastric junction cancer
Authors: Yanagimoto Yoshitomo , Kurokawa Yukinori , Doki Yuichiro , Yoshikawa Takaki , Boku Narikazu , Terashima Masanori 
Published: March 2022

Abstract
Esophagogastric junction cancer is defined as adenocarcinoma with the epicenter within 5 cm of the esophagogastric junction in the West according to the Siewert classification. In contrast, it is defined as cancer of any histological type with the epicenter located within 2 cm proximal or distal to the esophagogastric junction in Japan according to the Nishi classification. Recently, the incidence of esophagogastric junction cancer has been rapidly rising all over the world, leading to much attention. Esophagogastric junction cancer was previously treated like gastric cancer or esophageal cancer because it is a less frequently occurring tumor. Esophagogastric junction cancer is considered to have worse prognosis than gastric cancer. Therefore, in recent years, esophagogastric junction cancer has been recognized as an independent malignant disease with poor prognosis, and thus development of treatment strategies focused on esophagogastric junction cancer is needed. The mapping of frequent metastasis in the mediastinal and abdominal lymph nodes has revealed the lymphatic flow from esophagogastric junction cancer specifically, establishing the optimal lymph node dissection area and surgical approach. The development of multimodal treatment that includes chemotherapy, radiotherapy and immunotherapy has been applied to improve the survival of esophagogastric junction cancer. In this review, we summarize clinical trials with important evidence on surgical and multimodal perioperative treatments for esophagogastric junction cancer.
Physician Dispensing Among Urology Practices and the Use of Abiraterone or Enzalutamide for Men With Advanced Prostate Cancer
Authors: Lai Lillian Y , Kaufman Samuel R , Oerline Mary K , Caram Megan E V , Maganty Avinash , Hollenbeck Brent K , Shahinian Vahakn B 
Published: March 2022

Abstract
Urologists are increasingly prescribing oral targeted therapies to patients with advanced prostate cancer. Concurrent with this trend, urology practices are allowing patients to fill their prescription onsite or through a pharmacy established by the practice. We examined prescription patterns for abiraterone or enzalutamide between eventually dispensing single-specialty urology practices, nondispensing single-specialty urology practices, and multispecialty practices using a 20% random sample of the 2013-2017 national Medicare claims. We determined physician dispensing through manual search of publicly available information. From 2015 through 2017, higher percentages of patients managed by eventually dispensing single-specialty urology practices had a filled prescription of abiraterone or enzalutamide compared with patients managed in nondispensing single-specialty urology practices (eg, in 2017, 8.9%, 95% confidence interval = 7.3% to 10.9%, vs 5.9%, 95% confidence interval = 5.0% to 7.0%, respectively; 2-sided P &lt; .001). Insofar as physician dispensing is associated with higher use of abiraterone or enzalutamide, it may represent a means to improve treatment access.
Development of Peer Relationships From Adolescence into Emerging Adulthood: Comparing Males and Females With and Without Type 1 Diabetes
Authors: Raymaekers Koen , Berg Cynthia A , Helgeson Vicki S 
Published: March 2022

Abstract

Objective
Friendships and romantic relationships are important sources of support that contribute to well-being for youth across adolescence and emerging adulthood and may be especially important for those with a chronic illness. We examined gender differences in trajectories of peer relationships among those with type 1 diabetes (T1D) and how they differ from those without.

Methods
Individuals with T1D (N = 132) and controls (N = 131) completed questionnaires across 11 years (M age = 12 years at baseline). Trajectories of friend support, conflict, and companionship were estimated from ages 11 to 23. Romantic support and conflict trajectories were estimated from ages 17 to 23.

Results
Females experienced more friend support than males, especially in comparison to males with T1D. Control females experienced highest levels of romantic support and lowest levels of romantic conflict. In comparison to control males, males with T1D experienced less friend support in early adolescence and less companionship in late adolescence and emerging adulthood. In comparison to control females, females with T1D experienced less friend support in late adolescence and more romantic conflict in emerging adulthood.

Conclusions
Findings that males with T1D report less friend support and companionship compared to control males, and females with T1D report less friend support and more romantic conflict than control females are of concern as these results suggest those with T1D may be missing out on important aspects of peer relationships. Understanding the broader social network of peer relationships may be useful to clinicians as they assist individuals in garnering support in general and for their diabetes.
Challenging diagnosis of cervical vagal nerve schwannoma
Authors: Pankratjevaite Lina , Dreyer Niloofar Sherazi , Dauksa Albertas , Sarauskas Valdas 
Published: March 2022

Abstract
Schwannoma arising from vagal nerve is a rare tumour. It is a slow-growing, benign mass, but rarely it might undergo malignant transformation. We report a case of a 55-year-old woman with asymptomatic Xth cranial nerve schwannoma in the left side of the neck. Initially, during the ultrasound examination, the tumour was misconceived to be a malignant lymph node. The patient underwent complete surgical excision of it. Histopathological examination revealed typical features of schwannoma. Clinical diagnose of cervical vagal nerve schwannoma is difficult. Magnetic resonance imaging is as an accurate diagnostic tool for these tumours. Surgical excision is the treatment of choice.
Facultative heterochromatin formation in rDNA is essential for cell survival during nutritional starvation
Authors: Hirai Hayato , Takemata Naomichi , Tamura Miki , Ohta Kunihiro 
Published: March 2022

Abstract
During the cellular adaptation to nutrient starvation, cells temporarily decelerate translation processes including ribosomal biogenesis. However, the mechanisms repressing robust gene expression from the ribosomal gene cluster (rDNA) are unclear. Here, we demonstrate that fission yeast cells facing glucose starvation assemble facultative heterochromatin in rDNA leading to its transcriptional repression. Glucose starvation induces quick dissociation of the ATF/CREB-family protein Atf1 from rDNA, where in turn the histone chaperone FACT is recruited to promote H3K9 methylation and heterochromatinization. We also identify the histone acetyltransferase Gcn5 as a repressor of rDNA heterochromatinization in glucose-rich conditions, and this protein dissociates from rDNA upon glucose starvation. Facultative heterochromatin formation in rDNA requires histone deacetylases Clr3 and both the RNAi-dependent and -independent gene silencing pathways. This is essential in adaptation to starvation since mutants lacking heterochromatin formation in rDNA lead to untimely cell death during glucose starvation.
Genetic control of branching patterns in grass inflorescences
Authors: Kellogg Elizabeth A 
Published: March 2022

Abstract
Inflorescence branching in the grasses controls the number of florets and hence the number of seeds. Recent data on the underlying genetics come primarily from rice and maize, although new data are accumulating in other systems as well. This review focuses on a window in developmental time from the production of primary branches by the inflorescence meristem through to the production of glumes, which indicate the transition to producing a spikelet. Several major developmental regulatory modules appear to be conserved among most or all grasses. Placement and development of primary branches are controlled by conserved auxin regulatory genes. Subtending bracts are repressed by a network including TASSELSHEATH4, and axillary branch meristems are regulated largely by signaling centers that are adjacent to but not within the meristems themselves. Gradients of SQUAMOSA-PROMOTER BINDING-like and APETALA2-like proteins and their microRNA regulators extend along the inflorescence axis and the branches, governing the transition from production of branches to production of spikelets. The relative speed of this transition determines the extent of secondary and higher order branching. This inflorescence regulatory network is modified within individual species, particularly as regards formation of secondary branches. Differences between species are caused both by modifications of gene expression and regulators and by presence or absence of critical genes. The unified networks described here may provide tools for investigating orphan crops and grasses other than the well-studied maize and rice.
Integrative analyses identify potential key genes and calcium-signaling pathway in familial AVNRT using whole-exome sequencing
Authors: Huang Jichang , Luo Rong , Zheng Chenqing , Cao Xin , Zhu Yuncai , He Tao , Liu Mingjiang , Yang Zhenglin , Wu Xiushan , Li Xiaoping 
Published: March 2022

AbstractBackgroundAtrioventricular nodal reentrant tachycardia (AVNRT) is a common arrhythmia. Growing evidence suggests that family aggregation and genetic factors are involved in AVNRT. However, in families with a history of AVNRT, disease-causing genes have not been reported.ObjectiveTo investigate the genetic contribution of familial AVNRT using a WES approach.MethodsBlood samples were collected from 20 patients from nine families with a history of AVNRT and 100 control participants, and we systematically analyzed mutation profiles using whole-exome sequencing. Gene-based burden analysis, integration of previous sporadic AVNRT data, pedigree-based co-segregation, protein-protein interaction network analysis, single-cell RNA sequencing, and confirmation of animal phenotype were performed.ResultsAmong 95 reference genes, seven pathogenic genes have been identified both in sporadic and familial AVNRT, including CASQ2, AGXT, ANK2, SYNE2, ZFHX3, GJD3, and SCN4A. Among the 37 reference genes from sporadic AVNRT, five pathogenic genes were identified in patients with both familial and sporadic AVNRT: LAMC1, RYR2, COL4A3, NOS1, and ATP2C2. Considering the unique internal pathogenic gene within pedigrees, three genes, TRDN, CASQ2, and WNK1, were likely to be the pathogenic genes in familial AVNRT. Notably, the core calcium-signaling pathway may be closely associated with the occurrence of AVNRT, including CASQ2, RYR2, TRDN, NOS1, ANK2, and ATP2C2.ConclusionThese results revealed the underlying mechanism for familial AVNRT.
Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity
Authors: Sefik Esra , Guest Ryan M. , Aberizk Katrina , Espana Roberto , Goines Katrina , Novacek Derek M. , Murphy Melissa M. , Goldman-Yassen Adam E. , Cubells Joseph F. , Ousley Opal , Li Longchuan , Shultz Sarah , Walker Elaine F. , Mulle Jennifer G. 
Published: March 2022

AbstractThe 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis- risk (>40-fold). Systematic research offers promising avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. Here, we report the first in- depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). By neuroimaging, we also explore correlations between psychotic symptoms and posterior fossa abnormalities in 3q29Del. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms, with select sex differences. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in elevated psychosis-risk.HighlightsThe rare copy number variants (CNVs) 3q29Del and 22q11.2Del confer the largest known effect sizes for schizophrenia susceptibility.While 22q11.2Del’s link with psychosis has been extensively studied, in-depth characterization of psychotic symptoms associated with 3q29Del is lacking.This study fills this gap and provides the first phenotypic comparison of psychotic symptom profiles in carriers of these CNVs, and healthy controls.Additionally, we uncover a novel genetic association between 3q29Del, psychotic symptoms, and cerebellar cortex development.
Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells
Authors: Murtha Kaitlin E. , Yang Yang , Ceriani Federico , Jeng Jing-Yi , Climer Leslie K. , Jones Forrest , Charles Jack , Devana Sai K. , Hornak Aubrey J. , Marcotti Walter , Simmons Dwayne D. 
Published: March 2022

AbstractIn cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), α-parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm-/-) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ transients than those elicited in cells from Ocm-/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm-/-;Apv-/-), mutant OHCs show even faster Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and in transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.
Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication
Authors: Kladnik Jerneja , Dolinar Ana , Kljun Jakob , Perea David , Grau-Expósito Judith , Genescà Meritxell , Novinec Marko , Buzon Maria J. , Turel Iztok 
Published: March 2022

AbstractAs SARS-CoV-2 triggered a global health crisis, there is an urgent need to provide patients with safe, effective, accessible, and preferably oral therapeutics for COVID-19 that complement mRNA vaccines. Zinc compounds are widely known for their antiviral properties. Therefore, we have prepared a library of zinc complexes with pyrithione (1-hydroxy-2(1H)-pyridinethione) and its analogues, all of which showed promising in vitro inhibition of cathepsin L, an enzyme involved in SARS-CoV-2 entry, and PLPro, an enzyme involved in SARS-CoV-2 replication both in (sub)micromolar range. Zinc pyrithione 1a is a well-established, commercially available antimicrobial agent and was therefore selected for further evaluation of its SARS-CoV-2 entry and replication inhibition in an ex vivo system derived from primary human lung tissue. Our results suggest that zinc pyrithione complex 1a provides a multitarget approach to combat SARS-CoV-2 and should be considered for repurposing as a potential therapeutic against the insidious COVID-19 disease.Featured imageIn our study, we show that zinc pyrithione holds immense potential for the development of a possible out-patient treatment for SARS-CoV-2 due to its inhibition of viral entry and replication.
ACCUMULATION OF MICROPLASTIC AND MICRORUBBER PARTICLES IN STORMWATER POND FISH AND INVERTEBRATES
Authors: LaPlaca Stephanie B. , van den Hurk Peter 
Published: March 2022

AbstractStormwater ponds serve as best management practices to trap or remove both physical and chemical pollutants before further discharge of stormwater into receiving natural waterbodies. Stormwater ponds can therefore accumulate high levels of pollutants, including microplastics (MP) and microrubber (MR) from road runoff. It was hypothesized that biota in stormwater ponds that receive large amounts of road runoff, or are in proximity to roadways and major developments, would contain significant amounts of MP per individual, with high abundances of tire particles (TP). Fish and invertebrates were collected from five stormwater ponds and their adjacent tidal creeks in Mt. Pleasant, SC, USA. Whole organisms were digested using KOH and digested contents were filtered and analyzed by visual microscopy to identify and count MPs.The majority (>80%) of MP recovered from biota across all sites were suspected TP. The average number of MP per individual ranged from 0.3 to 71 MP and the average number of suspected tire particles per individual ranged from 0 to 57.7 tire particles.There were significant differences in MP per individual observed between sites and between species. A combination of factors such as availability of MPs based on surrounding land use, pond hydrodynamics, organism size, and species feeding habitat likely influenced the total MP observed among the different sites and species analyzed. These data provide preliminary examination into the fate and transport of MP and MR in stormwater ponds and an evaluation of MP and MR abundance in organisms from stormwater ponds in the coastal zone.
Maternal immune activation and adolescent alcohol exposure increases alcohol drinking and disrupts cortical-striatal-hippocampal oscillations in adult offspring
Authors: Henricks Angela M , Sullivan Emily DK , Dwiel Lucas L , Li Judy Y , Wallin Diana J , Khokhar Jibran Y. , Doucette Wilder T 
Published: March 2022

AbstractMaternal immune activation (MIA) is strongly associated with an increased risk of developing mental illness in adulthood, which often co-occurs with alcohol misuse. The current study aimed to begin to determine whether MIA, combined with adolescent alcohol exposure (AE), could be used as a model with which we could study the neurobiological mechanisms behind such co-occurring disorders. Pregnant Sprague-Dawley rats were treated with PolyI:C or saline on gestational day 15. Half of the offspring were given continuous access to alcohol during adolescence, leading to four experimental groups: controls, MIA, AE, and Dual (MIA + AE). We then evaluated whether MIA and/or AE alters: 1) alcohol consumption; and 2) cortical-striatal-hippocampal oscillations in adult offspring. Dual rats, particularly females, drank significantly more alcohol in adulthood compared to all other groups. Using machine learning to build predictive models from oscillations, we were able to differentiate Dual rats from control rats and AE rats in both sexes, and Dual rats from MIA rats in females. The current data suggest that MIA+AE (Dual “hits”) is a valuable model that we can use to study the neurobiological underpinnings of co-occurring disorders. Our future work aims to extend these findings to other addictive substances to enhance the translational relevance of this model.
The role of TGFβ signaling in Gli1+ tendon and enthesis cells
Authors: Song Lee , Golman Mikhail , Abraham Adam C. , Zelzer Elazar , Thomopoulos Stavros 
Published: March 2022

ABSTRACTThe development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGFβ signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGFβ signaling in Gli1+ cell function, the receptor for TGFβ, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGFβ signaling in these cells led to defects in enthesis formation by P56, including deficient bone morphometry underlying the enthesis and decreased mechanical properties.In vitroexperiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGFβ controls cell proliferation and differentiation through canonical and non-canonical pathways and that TGFβ directly controls the tendon transcription factor scleraxis by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.