bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paul and Sacred Space
Authors: Økland Jorunn 
Published: August 2021

AbstractThis chapter analyses the terms with which Paul of Tarsus designates various sacred spaces—hieron, naos, eidoleion, ekklesia—in conversation with the archaeology of sacred spaces, research on the Pauline house churches, and with the help of theories of space, new materialism, and the sacred. The chapter starts with an introduction of the analytical frameworks and ends with ideas about ‘monumentalization’: that the social-structural relations between people in a sacred space tended to materialize over time into purpose-built buildings—hence the double meanings of synagogue, ekklesia, and hieron as designations both of assemblies and later of the buildings accommodating the respective assemblies. A central argument is that Paul’s letters constitute a special case in the development of the early Christian ekklesia and the parallel development of the synagogue, because in Paul’s time the temple in Jerusalem was still standing and was a self-evident part of his religious universe.
Long-term repetitive exposure to excess iodine induces mitochondrial apoptosis, and alters monoamine neurotransmitters in hippocampus of rats of different genders
Authors: Cui Yushan , Zhang Bin , Zhang Zushan , Nie Junyan , Liu Hongliang 
Published: August 2021

AbstractThe influence of excess iodine on human health has been paid more and more attention. Although numerous studies have reported that excess iodine may cause deleterious effects, the mental damage and its mechanism is yet to be identified. Using Sprague-Dawley rats exposed to excess iodine from pregnancy to 6 months post-delivery as in vivo model, this study explored the impacts of long-term repetitive excess iodine administration on the hippocampus of offspring rats, focusing on mitochondrial apoptosis pathway, with changes in monoamine neurotransmitters. The results showed that excess iodine could increase urinary iodine and brain organ coefficient in offspring of both genders, change the hippocampal cell structure, and damage the spatial learning and memory capacities. Poly ADP-ribose polymerase (PARP), P53, Cleaved Caspase-3, and cytochrome C proteins expression increased and Bcl2 protein expression decreased in hippocampus of excess iodine-treated offspring, indicating that excess iodine could activate the mitochondrial apoptosis pathway. Besides, excess iodine showed different effects on monoamine neurotransmitter in different gender. Collectively, our experimental data indicated that the learning and memory impairment induced by excess iodine may be mediated via mitochondrial apoptotic pathway. Long-term repetitive excess iodine exposure affected monoamine neurotransmitters in hippocampus of offspring rats.
Auxin concentration and xylem production of Pinus massoniana in a subtropical forest in south China
Authors: Guo Xiali , Huang Jian-Guo , Buttò Valentina , Luo Dawei , Shen Chunyu , Li Jingye , Liang Hanxue , Zhang Shaokang , Hou Xingliang , Zhao Ping , Rossi Sergio 
Published: August 2021

Abstract
Auxin is involved in various developmental processes of plants, including cell division in cambium and xylem differentiation. However, most studies linking auxin and xylem cell production are performed in environments with a strong seasonality (i.e., temperate and boreal climates). The temporal dynamics of auxin and cambial activity of subtropical trees remain basically unknown. In this study, we sampled four microcores weekly in three individuals of Chinese red pine (Pinus massoniana Lamb.) from February to December 2015–16 to compare xylem formation with auxin concentration in subtropical China. During the entire period of sampling, the number of cambial cells varied from 2 to 7, while the number of cells in the enlarging zone ranged from 1 to 4 and from 1 to 5 in the wall-thickening zone. In 2015, the average auxin concentration was 3.46 ng g−1, with 33 xylem cells being produced at the end of the year. In 2016, a lower auxin concentration (2.59 ng g−1) corresponded to a reduced annual xylem production (13.7 cells). No significant relationship between auxin concentration and number of xylem cells in differentiation was found at the weekly scale. Unlike in boreal and temperate forests, the lack of wood formation seasonality in subtropical forests makes it more difficult to reveal the relationship between auxin concentration and number of xylem cells in differentiation at the intra-annual scale. The frequent and repeated samplings might have reduced auxin concentration in the developing cambium and xylem, resulting in a lower xylem cell production.
Poacic acid, a β‐1,3‐glucan–binding antifungal agent, inhibits cell‐wall remodeling and activates transcriptional responses regulated by the cell‐wall integrity and high‐osmolarity glycerol pathways in yeast
Authors: García Raúl , Itto‐Nakama Kaori , Rodríguez‐Peña José Manuel , Chen Xiaolin , Sanz Ana Belén , de Lorenzo Alba , Pavón‐Vergés Mónica , Kubo Karen , Ohnuki Shinsuke , Nombela César , Popolo Laura , Ohya Yoshikazu , Arroyo Javier 
Published: August 2021

AbstractAs a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits β‐1,3‐glucan synthesis inSaccharomyces cerevisiaeand has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to β‐1,3‐glucan, its affinity for which is ~30‐fold that for chitin. Besides its effect on β‐1,3‐glucan synthase activity, PA inhibited the yeast glucan‐elongating activity of Gas1 and Gas2 and the chitin–glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co‐regulation was mediated by parallel activation of the cell‐wall integrity (CWI) and high‐osmolarity glycerol signaling pathways. Despite targeting β‐1,3‐glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent.
Atypic SUMOylation of Nor1/NR4A3 regulates neural cell viability and redox sensitivity
Authors: Gagnon Jonathan , Caron Véronique , Gyenizse Laurent , Tremblay André 
Published: August 2021

AbstractNeuron‐derived orphan receptor 1, NR4A3 (Nor1)/NR4A3 is an orphan nuclear receptor involved in the transcriptional control of developmental and neurological functions. Oxidative stress‐induced conditions are primarily associated with neurological defects in humans, yet the impact on Nor1‐mediated transcription of neuronal genes remains with unknown mechanism. Here, we demonstrate that Nor1 is a non‐conventional target of SUMO2/3 conjugation at Lys‐137 contained in an atypic ψKxSP motif referred to as the pSuM. Nor1 pSuM SUMOylation differs from the canonical process with the obligate phosphorylation of Ser‐139 by Ras signaling to create the required negatively charged interface for SUMOylation. Additional phosphorylation at sites flanking the pSuM is also mediated by the coordinated action of protein kinase casein kinase 2 to function as a small ubiquitin‐like modifier enhancer, regulating Nor1‐mediated transcription and proteasomal degradation. Nor1 responsive genes involved in cell proliferation and metabolism, such as activating transcription factor 3, cyclin D1, CASP8 and FADD‐like apoptosis regulator, and enolase 3 were upregulated in response to pSuM disruption in mouse HT‐22 hippocampal neuronal cells and human neuroblastoma SH‐SY5Y cells. We also identified critical antioxidant genes, such as catalase, superoxide dismutase 1, and microsomal glutathione S‐transferase 2, as responsive targets of Nor1 under pSuM regulation. Nor1 SUMOylation impaired gene transcription through less effective Nor1 chromatin binding and reduced enrichment of histone H3K27ac marks to gene promoters. These effects resulted in decreased neuronal cell growth, increased apoptosis, and reduced survival to oxidative stress damage, underlying the role of pSuM‐modified Nor1 in redox homeostasis. Our findings uncover a hierarchical post‐translational mechanism that dictates Nor1 non‐canonical SUMOylation, disrupting Nor1 transcriptional competence, and neuroprotective redox sensitivity.
Ablation of PDE4B protects from Pseudomonas aeruginosa‐induced acute lung injury in mice by ameliorating the cytostorm and associated hypothermia
Authors: Abou Saleh Lina , Boyd Abigail , Aragon Ileana V. , Koloteva Anna , Spadafora Domenico , Mneimneh Wadad , Barrington Robert A. , Richter Wito 
Published: August 2021

AbstractPseudomonas aeruginosa is a frequent cause of hospital‐acquired lung infections characterized by hyperinflammation, antibiotic resistance, and high morbidity/mortality. Here, we show that the genetic ablation of one cAMP‐phosphodiesterase 4 subtype, PDE4B, is sufficient to protect mice from acute lung injury induced by P aeruginosa infection as it reduces pulmonary and systemic levels of pro‐inflammatory cytokines, as well as pulmonary vascular leakage and mortality. Surprisingly, despite dampening immune responses, bacterial clearance in the lungs of PDE4B‐KO mice is significantly improved compared to WT controls. In wildtypes, P aeruginosa‐infection produces high systemic levels of several cytokines, including TNF‐α, IL‐1β, and IL‐6, that act as cryogens and render the animals hypothermic. This, in turn, diminishes their ability to clear the bacteria. Ablation of PDE4B curbs both the initial production of acute response cytokines, including TNF‐α and IL‐1β, as well as their downstream signaling, specifically the induction of the secondary‐response cytokine IL‐6. This synergistic action protects PDE4B‐KO mice from the deleterious effects of the P aeruginosa‐induced cytostorm, while concurrently improving bacterial clearance, rather than being immunosuppressive. These benefits of PDE4B ablation are in contrast to the effects resulting from treatment with PAN‐PDE4 inhibitors, which have been shown to increase bacterial burden and dissemination. Thus, PDE4B represents a promising therapeutic target in settings of P aeruginosa lung infections.
Disruption of lateral hypothalamic calorie detection by a free choice high fat diet
Authors: Koekkoek Laura L. , Slomp Margo , Castel Julien , Mutersbaugh Michael , Linville Ian , Serlie Mireille J. , Luquet Serge H. , la Fleur Susanne E. 
Published: August 2021

AbstractDuring the last few decades, the consumption of low‐calorie sweeteners, as a substitute for caloric sweeteners, has sharply increased. Although research shows that caloric versus low‐calorie sweeteners can have differential effects on the brain, it is unknown which neuronal populations are responsible for detecting the difference between the two types of sweeteners. Using in vivo two‐photon calcium imaging, we investigated how drinking sucrose or sucralose (a low‐calorie sweetener) affects the activity of glutamatergic neurons in the lateral hypothalamus. Furthermore, we explored the consequences of consuming a free‐choice high fat diet on the calorie detection abilities of these glutamatergic neurons. We found that glutamatergic neurons indeed can discriminate sucrose from water and sucralose, and that consumption of a free‐choice high fat diet shifts the glutamatergic neuronal response from sucrose‐specific to sucralose‐specific, thereby disrupting calorie detection. These results highlight the disruptive effects of a diet high in saturated fat on calorie detection in the lateral hypothalamus.
Differential Gateways, Facilitators, and Barriers to Substance Use Disorder Treatment for Pregnant Women and Mothers: A Scoping Systematic Review
Authors: Choi Sugy , Rosenbloom David , Stein Michael D. , Raifman Julia , Clark Jack A. 
Published: August 2021

Objectives
Access to substance use disorder (SUD) treatment is complex, and more so for pregnant women and mothers who experience unique barriers. This scoping systematic review aimed to summarize contemporary findings on gateways, facilitators, and barriers to treatment for pregnant women and mothers with SUD.

Methods
We used the scoping review methodology and a systematic search strategy via MEDLINE/PubMed and Google Scholar. The search was augmented by the similar article lists for sources identified in PubMed. Scholarly and peer-reviewed articles that were published in English from 1996 to 2019 were included. A thematic analysis of the selected studies was used to summarize pathways to SUD treatment and to identify research gaps.

Results
The analysis included 41 articles. Multiple gateway institutions were identified: health care settings, social service agencies, criminal justice settings, community organizations, and employers. Some of the identified facilitators and barriers to SUD treatment were unique to pregnant women and mothers (eg, fear of incarceration for child abuse). Both personal (emotional support and social support) and child-related factors (loss of children, suspension or termination of parental rights, the anticipation of reuniting with children) motivated women to seek treatment. Major access barriers included fear, stigma, charges of child abuse, inconvenience, and financial hardship.

Conclusions
There has been progress in implementing different types of interventions and treatments for that were attentive to pregnant women and mothers’ needs. We developed a conceptual model that characterized women’s pathways to treatment by deciphering women’s potential engagement in gateway settings.
A Population-based Study of Treatment Patterns and Survival of Patients With De Novo Stage IV Non–Small Cell Lung Cancer
Authors: Batra Atul , Yusuf Dimas , Hurry Manjusha , Walton Ryan N. , Devost Natalie , Farrer Christie , Cheung Winson Y. 
Published: August 2021

Background:
Treatment strategies for metastatic non–small cell lung cancer (NSCLC) are evolving rapidly and can be highly variable. Real-world evidence of treatment patterns and outcomes can provide an understanding of our current practice and offer insights on ways to incorporate emerging therapies into our treatment paradigm. In this population-based study, we investigated treatments and outcomes of stage IV NSCLC patients from a large Canadian province.

Methods:
Patients diagnosed with de novo stage IV NSCLC from April 1, 2010 to March 31, 2015 were identified. Data for baseline characteristics, treatments, and outcomes were obtained from provincial data sources, including the cancer registry and electronic medical records. We classified systemic treatments as chemotherapy, targeted therapy (anti-epidermal growth factor receptor, and anti-anaplastic lymphoma kinase) and immunotherapy (checkpoint inhibitors) and characterized clinical outcomes by treatment type.

Results:
A total of 6438 patients were identified with NSCLC, of whom 3606 (56%) had de novo stage IV disease. The median age of diagnosis was 69 (range: 20 to 100) years and 52.4% were men. First-line palliative treatments included: chemotherapy in 19.5% (n=703), targeted agents in 5.7% (n=204), immunotherapy in 1% (n=1), radiotherapy in 6.8% (n=246), and best supportive care in 74.8% (n=2,698). Median overall survival (mOS) from diagnosis for the whole cohort was 3.8 months. Within subgroups, mOS was 18.0 months for targeted therapies, 9.4 months for chemotherapy, and 2.5 months for best supportive care. Only 1.0% of patients (n=34) received immunotherapy at any line.

Conclusions:
Survival benefit was dependent on type of treatment received, with significantly better mOS observed with the use of small-molecule targeted therapy against epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements, as compared with best supportive care.
Management of Early-Stage Rectal Cancer
Authors: Greco Justin M. , Abelson Jonathan S. 
Published: August 2021

Case Summary:
A 59-year-old man underwent screening colonoscopy that identified a 2-cm rectal polyp in the posterior midline, 7 cm from the anal verge. Biopsy revealed a tubular adenoma with high-grade dysplasia. The patient underwent a robotic-assisted transanal minimally invasive surgery with full-thickness excision (Fig. 1). Final pathology confirmed a well-differentiated adenocarcinoma extending into the submucosa (sm2). There was no lymphovascular or perineural invasion, and the radial margin was 5 mm.
Evaluation and usability study of low-cost laparoscopic box trainer “Lap-Pack”: a 2-stage multicenter cohort study
Authors: Chauhan Manish , Sawhney Riya , Da Silva Carolina F. , Aruparayil Noel , Gnanaraj Jesudian , Maiti Sukumar , Mishra Anurag , Quyn Aaron , Bolton William , Burke Joshua , Jayne David , Valdastri Pietro 
Published: August 2021

Introduction:
Laparoscopic training is restricted in low resource settings due to limited access to specialist training equipment and financial constraints. This study aimed to evaluate simulation skills and usability of an original low-cost laparoscopic trainer, the “Lap-Pack,” developed at the University of Leeds, UK.

Methods:
Stage I evaluation was conducted in Kolkata (India) between March, 12 and 14, 2019. Laparoscopic simulation training was based on the 5 domains of fundamentals of laparoscopic surgery (FLS), which assessed skill acquisition across 7 rural surgeons from North-East India. The McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) criteria was used to statistically analyze trainee performance between pretraining and posttraining sessions. Also, Lap-Pack was qualitatively compared with a commercial box trainer, Inovus Pyxus HD (IPHD). Stage II involved a multi-center usability study in 2 centers of India and the United Kingdom (2019). Seventy-eight participants performed 2 FLS tasks using Lap-Pack and provided scores on a 25-point questionnaire, including a preestablished Face-Validity Criteria and 4 evaluation categories—Usability, Camera, View, and, Material.

Results:
In stage I, the total posttraining MISTELS score for Lap-Pack was higher, that is 773.37 (SD: 183.67) than pretraining score, that is 351.2 (SD: 471.5). The posttraining scores showed laparoscopic skill acquisition with statistically significant (P<0.05) difference for precision cutting, intracorporeal and extracorporeal knot. In stage II, Lap-Pack scored highly in Face-Validity with a combined mean score of 4.81 [95% confidence interval (CI): 4.52–5.09, P<0.05] out of a possible 6. It scored highest (scale: 1=low to 7=high) in Usability 6.14 (95% CI: 6.05–6.22, P<0.05) and Camera 6.14 (95% CI: 6.01–6.27, P<0.05). The “Lightweight” (6.46, 95% CI: 6.32–6.60, P<0.05) and “Portability” (6.35, 95% CI: 6.18–6.51, P<0.05) features of Lap-Pack were appreciated.

Conclusion:
The Lap-Pack is a suitable low fidelity simulator for laparoscopic training in a low-resource setting.
Opportunities for Closing the Gap in HIV Diagnosis, Treatment, and Viral Load Suppression in Children in Malawi: Results From a 2015–2016 Population-based HIV Impact Assessment Survey
Authors: Jonnalagadda Sasi , Auld Andrew , Jahn Andreas , Saito Suzue , Bello George , Sleeman Katrina , Ogollah Francis M. , Cuervo-Rojas Juliana , Radin Elizabeth , Kayira Dumbani , Kim Evelyn , Payne Danielle , Burnett Janet , Hrapcak Susan , Patel Hetal , Voetsch Andrew C. ,   for the MPHIA Study Team
Published: August 2021

Background:
Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015–2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression.

Methods:
In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection.

Results:
Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1–1.9) and 8.0% (95% CI: 5.6–10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028–149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3–41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8–95.6) were on ART and 57.9% (95% CI: 41.4–74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0–70.5) had unsuppressed VL.

Conclusions:
Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions.
Positive affect and distraction enhance whereas negative affect impairs pain modulation in patients with recurrent low back pain and matched controls
Authors: McPhee Megan E. , Graven-Nielsen Thomas 
Published: August 2021

Abstract
Pathophysiological causes of low back pain (LBP) remain generally unclear, so focus has shifted to psychosocial features and central pain processing. Effects of attentional and affective manipulation on conditioned pain modulation and tonic pain perception were examined in 30 patients with recurrent LBP in 2 sessions, one with and one without clinical pain, and compared with healthy participants. Phasic cuff pressure on one leg, scored on a Numerical Rating Scale, was used for test stimuli, and contralateral tonic cuff pain rated on an electronic Visual Analogue Scale was the conditioning stimulus (CS). Test stimuli were assessed before and during (1) control with no manipulation or CS, (2) 3 attentional manipulations (Flanker with or without CS or CS-Only), and (3) 3 affective manipulations (positive, neutral, and negative images) with CS. Greater inhibition of test stimuli Numerical Rating Scale scores was observed in CS-only (P = 0.028), combined CS&attention (P = 0.026), and CS&Positive (P = 0.006) than control paradigms, and greater in CS&Positive (P = 0.019) than CS&Negative paradigms. Electronic Visual Analogue Scale scores of CS pain increased throughout all paradigms with CS (P < 0.05), except the CS&Positive paradigm, and greater facilitation was observed in the CS-Only paradigm than all others (P < 0.02), and lower facilitation was additionally observed in the CS&Positive paradigm compared with CS&Attention and CS&Negative paradigms (P < 0.01). Flanker effects and interruptive effects of CS pain on attention were observed consistent with prior findings, and affective manipulation produced less shift in valence among people with recurrent LBP than controls (P < 0.05). Attention and positive affect with CS pain evoked conditioned pain modulation, and all attentional or affective tasks, especially positive affect, reduced facilitation of CS pain.