bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant mediastinal mediobasal segmental pulmonary artery in a patient with lung cancer undergoing right lower lobectomy: a case report
Authors: Komori Kazuyuki , Hashimoto Hiroshi , Yoshikawa Kotaro , Kameda Koji , Taguchi Shinichi , Ozeki Yuichi
Published: April 2022

Background

A mediastinal mediobasal segmental pulmonary artery (A7) from the right main pulmonary artery is extremely rare.

Case presentation

We report the case of a 71-year-old woman with an aberrant mediastinal A7 who underwent right lower lobectomy for lung cancer (cT1bN0M0, stage IA2). Preoperative three-dimensional computed tomography (CT) angiography revealed an aberrant mediastinal A7 in the right main pulmonary artery. Right lower lobectomy and mediastinal lymph node dissection were performed. Intraoperatively, A7 was observed between the superior and inferior pulmonary veins and in the front of the lower bronchus near the anterior hilum. The artery was carefully dissected from the caudal side after inferior pulmonary vein dissection. The lung parenchyma, which was within the fissure due to poor lobulation between the middle and lower lobes, was safely divided.

Conclusions

Thoracic surgeons need to carefully evaluate CT angiography or enhanced multidetector CT findings at preoperative conferences and always keep this anomaly in mind.
Angong Niuhuang Wan reduces hemorrhagic transformation and mortality in ischemic stroke rats with delayed thrombolysis: involvement of peroxynitrite-mediated MMP-9 activation
Authors: Chen Hansen , Luo Yunxia , Tsoi Bun , Gu Bing , Qi Suhua , Shen Jiangang
Published: April 2022

Background

Hemorrhagic transformation (HT) is a common complication of delayed tissue plasminogen activator (t-PA) treatment for ischemic stroke. Peroxynitrite plays an important role in the breakdown of blood–brain barrier (BBB) and the development of HT. We tested the hypothesis that Angong Niuhuang Wan (AGNHW), a traditional Chinese medicinal formula, could be used in conjunction with t-PA to protect the BBB, minimize HT, and improve neurological function by suppressing peroxynitrite-mediated matrix metalloproteinase-9 (MMP-9) activation.

Methods

We first performed quality control study and chemical identification of AGNHW by using UPLC. In animal experiments, male Sprague–Dawley rats were subjected to 5 h of middle cerebral artery occlusion (MCAO) followed by 19 h of reperfusion plus t-PA infusion (10 mg/kg) at 5 h of cerebral ischemia. AGNHW (257 mg/kg) was given orally at 2 h after MCAO. Hemorrhagic transformation was measured using hemorrhagic scores and hemoglobin levels in ischemic brains. Evans blue leakage was utilized to assess the severity of the blood–brain barrier (BBB) damage. The modified neurologic severity score (mNSS) test was used to assess neurological functions. Peroxynitrite and superoxide was detected by using fluorescent probes. MMP-9 activity and expression were examined by gelatin zymography and immunostaining. The antioxidant effects were also studied by using brain microvascular endothelial b.End3 cells exposed to 5 h of oxygen and glucose deprivation (OGD) plus 5 h of reoxygenation with t-PA treatment (20 µg/ml).

Results

AGNHW significantly reduced the BBB damage, brain edema, reduced hemorrhagic transformation, enhanced neurological function, and reduced mortality rate in the ischemic stroke rats with t-PA treatment. AGNHW reduced peroxynitrite and superoxide in vivo and in vitro and six active chemical compounds were identified from AGNHW with peroxynitrite scavenging activity. Furthermore, AGNHW inhibited MMP-9 activity, and preserved tight junction protein claudin-5 and collagen IV in the ischemic brains.

Conclusion

AGNHW could be a potential adjuvant therapy with t-PA to protect the BBB integrity, reduce HT, and improve therapeutic outcome in ischemic stroke treatment via inhibiting peroxynitrite-mediated MMP-9 activation.

Graphical Abstract
Genetic insight into Birt–Hogg–Dubé syndrome in Indian patients reveals novel mutations at FLCN
Authors: Ray Anindita , Chattopadhyay Esita , Singh Richa , Ghosh Saurabh , Bera Arnab , Sarma Mridul , Munot Mahavir , Desai Unnati , Rajan Sujeet , Prabhudesai Pralhad , Prakash Ashish K. , Roy Chowdhury Sushmita , Bhowmick Niladri , Dhar Raja , Udwadia Zarir F. , Dey Atin , Mitra Subhra , Joshi Jyotsna M. , Maitra Arindam , Roy Bidyut
Published: April 2022

Background

Birt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma (chromophobe). Here, we comprehensively studied the mutational background of 31 clinically diagnosed BHDS patients and their 74 asymptomatic related members from 15 Indian families.

Results

Targeted amplicon next-generation sequencing (NGS) and Sanger sequencing of FLCN in patients and asymptomatic members revealed a total of 76 variants. Among these variants, six different types of pathogenic FLCN mutations were detected in 26 patients and some asymptomatic family members. Two of the variants were novel mutations: an 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and a splice acceptor mutation (c.1301-1G > A). Two variants were Clinvar reported pathogenic mutations: a stop-gain (c.634C > T) and a 4-nucleotide duplication (c.1329_1332dupAGCC). Two known variants were: hotspot deletion (c.1285delC) and a splice donor mutation (c.1300 + 1G > A). FLCN mutations could not be detected in patients and asymptomatic members from 5 families. All these mutations greatly affected the protein stability and FLCN-FNIP2 interaction as observed by molecular docking method. Family-based association study inferred pathogenic FLCN mutations are significantly associated with BHDS.

Conclusion

Six pathogenic FLCN mutations were detected in patients from 10 families out of 15 families in the cohort. Therefore, genetic screening is necessary to validate the clinical diagnosis. The pathogenic mutations at FLCN affects the protein–protein interaction, which plays key roles in various metabolic pathways. Since, pathogenic mutations could not be detected in exonic regions of FLCN in 5 families, whole genome sequencing is necessary to detect all mutations at FLCN and/or any undescribed gene/s that may also be implicated in BHDS.
Small fiber involvement is independent from clinical pain in late-onset Pompe disease
Authors: Enax-Krumova Elena K. , Dahlhaus Iris , Görlach Jonas , Claeys Kristl G. , Montagnese Federica , Schneider llka , Sturm Dietrich , Fangerau Tanja , Schlierbach Hannah , Roth Angela , Wanschitz Julia V. , Löscher Wolfgang N. , Güttsches Anne-Katrin , Vielhaber Stefan , Hasseli Rebecca , Zunk Lea , Krämer Heidrun H. , Hahn Andreas , Schoser Benedikt , Rosenbohm Angela , Schänzer Anne
Published: April 2022

Background

Pain occurs in the majority of patients with late onset Pompe disease (LOPD) and is associated with a reduced quality of life. The aim of this study was to analyse the pain characteristics and its relation to a small nerve fiber involvement in LOPD patients.

Methods

In 35 patients with LOPD under enzyme replacement therapy without clinical signs of polyneuropathy (19 females; 51 ± 15 years), pain characteristics as well as depressive and anxiety symptoms were assessed using the PainDetect questionnaire (PDQ) and the hospital anxiety and depression scale (HADS), respectively. Distal skin biopsies were analysed for intraepidermal nerve fiber density (IENFD) and compared to age- and gender-matched reference data. Skin biopsies from 20 healthy subjects served as controls to assure validity of the morphometric analysis.

Results

Pain was reported in 69% of the patients with an average intensity of 4.1 ± 1.1 on the numeric rating scale (NRS; anchors: 0–10). According to PDQ, neuropathic pain was likely in one patient, possible in 29%, and unlikely in 67%. Relevant depression and anxiety symptoms occurred in 31% and 23%, respectively, and correlated with pain intensity. Distal IENFD (3.98 ± 1.95 fibers/mm) was reduced in 57% of the patients. The degree of IENFD reduction did not correlate with the durations of symptoms to ERT or duration of ERT to biopsy.

Conclusions

Pain is a frequent symptom in treated LOPD on ERT, though a screening questionnaire seldom indicated neuropathic pain. The high frequency of small nerve fiber pathology in a treated LOPD cohort was found regardless of the presence of pain or comorbid risk factors for SFN and needs further exploration in terms of clinical context, exact mechanisms and when developing novel therapeutic options for LOPD.
School educational models and child mental health among K-12 students: a scoping review
Authors: Yu Ting , Xu Jian , Jiang Yining , Hua Hui , Zhou Yulai , Guo Xiangrong
Published: April 2022

Background

The promotion of mental health among children and adolescents is a public health imperative worldwide, and schools have been proposed as the primary and targeted settings for mental health promotion for students in grades K-12. This review sought to provide a comprehensive understanding of key factors involved in models of school education contributing to student mental health development, interrelationships among these factors and the cross-cultural differences across nations and societies.

Methods

This scoping review followed the framework of Arksey and O’Malley and holistically reviewed the current evidence on the potential impacts of school-related factors or school-based interventions on student mental health in recent 5 years based on the PubMed, Web of Science, Embase and PsycExtra databases.

Results/findings

After screening 558 full-texts, this review contained a total of 197 original articles on school education and student mental health. Based on the five key factors (including curriculum, homework and tests, physical activities, interpersonal relationships and after-school activities) identified in student mental development according to thematic analyses, a multi-component school educational model integrating academic, social and physical factors was proposed so as to conceptualize the five school-based dimensions for K-12 students to promote student mental health development.

Conclusions

The lessons learned from previous studies indicate that developing multi-component school strategies to promote student mental health remains a major challenge. This review may help establish appropriate school educational models and call for a greater emphasis on advancement of student mental health in the K-12 school context among different nations or societies.
Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy
Authors: Wu Huai-liang , Gong Yue , Ji Peng , Xie Yi-fan , Jiang Yi-Zhou , Liu Guang-yu
Published: April 2022

Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of nucleotide metabolism, our understanding of nucleotide metabolism in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness of nucleotide antimetabolites for enhancing immunotherapy. A growing body of evidence now supports the concept that targeting nucleotide metabolism can increase the antitumor immune response by (1) activating host immune systems via maintaining the concentrations of several important metabolites, such as adenosine and ATP, (2) promoting immunogenicity caused by increased mutability and genomic instability by disrupting the purine and pyrimidine pool, and (3) releasing nucleoside analogs via microbes to regulate immunity. Therapeutic approaches targeting nucleotide metabolism combined with immunotherapy have achieved exciting success in preclinical animal models. Here, we review how dysregulated nucleotide metabolism can promote tumor growth and interact with the host immune system, and we provide future insights into targeting nucleotide metabolism for immunotherapeutic treatment of various malignancies.
High expression of RIPK2 is associated with Taxol resistance in serous ovarian cancer
Authors: Shen Yuqing , Lin Hui , Chen Kelie , Ge Wanzhong , Xia Dajing , Wu Yihua , Lu Weiguo
Published: April 2022

Background

Taxol resistance in serous ovarian cancer is responsible for its poor prognosis, yet the underlying mechanism is still poorly understood. Thus, we probed the mechanism of Taxol resistance in serous ovarian cancer with multiple bioinformatic methods to provide novel insights into potential therapies.

Methods

The differentially expressed genes (DEGs) in Taxol-sensitive and Taxol-resistant cell lines and their relationship with the overall survival (OS) and progression-free interval (PFI) of ovarian cancer patients were analyzed using gene expression datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The role of receptor interacting serine/threonine kinase 2 (RIPK2) was validated via identification of its coexpressed genes, functional analysis and generation of a protein-protein interaction (PPI) network. The single sample gene set enrichment analysis (ssGSEA) was used to explore immune infiltration, and genomic alterations of RIPK2 were also analyzed via cBio Cancer Genomics Portal (cBioProtal).

Results

RIPK2 was highly expressed in Taxol resistant ovarian cancer cell lines, and its high expression was also linked with shorter OS and PFI in serous ovarian cancer patients. The PPI network analysis and pathway analysis demonstrated that RIPK2 might participate in the positive regulation of NF-κB transcription factor activity. RIPK2 expression was related to tumor microenvironment alterations, which might participate in the formation of Taxol resistance.

Conclusions

Our studies suggested that high expression of RIPK2 is related to Taxol resistance in serous ovarian cancer, and that RIPK2 induces Taxol resistance through NOD1/RIPK2/NF-κB inflammatory pathway activation and tumor microenvironment changes.
Effect of electroacupuncture on discomfort during gastroscopy: a study protocol for a randomized controlled trial
Authors: Yu Binyu , Hazlewood Philippa Jemma , Yin Xuan , Li Shanshan , Yue Hongyu , Xu Kun , Xu Shifen , Mi Yiqun
Published: April 2022

Background

Gastroscopy procedures are frequently performed under general sedation to minimize discomfort. Patients who refuse a sedative injection may experience more discomfort and adverse reactions such as pain and nausea. These instances reduce patient compliance and willingness to participate in future procedures. Acupuncture has been shown to have an anti-nausea and analgesic effect; however, there is limited data available that demonstrates the efficacy of acupuncture when applied before gastroscopy.

Methods

A total of 60 participants will be randomly assigned to the electroacupuncture (EA) group and the sham electroacupuncture (SEA) group at a ratio of 1:1. Acupuncture treatment will be performed before gastroscopy for a duration of 30 min. All patients will complete detailed questionnaires at 30 min and 7 days post-procedure to record the severity of their symptoms. The primary outcome will be the average of 4 standard visual analogue scale (VAS) scores in the categories of nausea, vomiting, throat discomfort, and agitation as reported by the patient. The secondary outcomes will be patient’s anxiety level as recorded by the 6-item short form of the State-Trait Anxiety Inventory (STAI-S6) and Amsterdam Pre-Operative Anxiety and Information Scale (APAIS), preference in a future endoscopy, pulse oxygen saturation (SpO2), heart rate (HR), and blood pressure (BP). Anxiety scales will be assessed before and after acupuncture; others will be completed at 30 min and 7 days post-procedure. The duration of the gastroscopy and the number of biopsies will be recorded after operation.

Discussion

This randomized controlled trial will explore the feasibility of the further clinical application of electroacupuncture for the improvement of patient discomfort during gastroscopy without systemic sedation.

Trial registration

ChiCTR2000040726. This trial has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2020SHL-KY-11). Registration date 12 August 2020.
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial
Authors: McGree J. M. , Hockham C. , Kotwal S. , Wilcox A. , Bassi A. , Pollock C. , Burrell L. M. , Snelling T. , Jha V. , Jardine M. , Jones M. ,   for the CLARITY Trial Steering Committee
Published: April 2022

The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease) is a two-arm, multi-centre, randomised controlled trial being run in India and Australia that investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The trial was designed as a Bayesian adaptive sample size trial with regular planned analyses where pre-specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here, we describe the statistical analysis plan for the trial and define the pre-specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment.

Trial registration

ClinicalTrials.govNCT04394117. Registered on 19 May 2020Clinical Trial Registry of India CTRI/2020/07/026831

Version and revisions

Version 1.0. No revisions.
The complete mitochondrial genomes of Paradiplozoon yarkandense and Paradiplozoon homoion confirm that Diplozoidae evolve at an elevated rate
Authors: Hao Cui-Lan , Arken Kadirden , Kadir Munira , Zhang Wen-Run , Rong Meng-Jie , Wei Nian-Wen , Liu Yan-Jun , Yue Cheng
Published: April 2022

Background

Diplozoidae are monogenean (Monogenea: Polyopisthocotylea) fish parasites characterised by a unique life history: two larvae permanently fuse into an X-shaped “Siamese” organism. Taxonomy and phylogeny of Diplozoidae and Polyopisthocotylea remain unresolved due to the unavailability of molecular markers with sufficiently high resolution. Mitogenomes may be a suitable candidate, but there are currently only 12 available for the Polyopisthocotylea (three for Diplozoidae). The only available study of diplozoid mitogenomes found unique base composition patterns and elevated evolution rates in comparison with other Monogenean mitogenomes.

Methods

To further explore their evolution and generate molecular data for evolutionary studies, we sequenced the complete mitogenomes of two Diplozoidae species, Paradiplozoon homoion and Paradiplozoon yarkandense, and conducted a number of comparative mitogenomic analyses with other polyopisthocotyleans.

Results

We found further evidence that mitogenomes of Diplozoidae evolve at a unique, elevated rate, which was reflected in their exceptionally long branches, large sizes, unique base composition, skews, and very low gene sequence similarity levels between the two newly sequenced species. They also exhibited remarkably large overlaps between some genes. Phylogenetic analysis of Polyopisthocotylea resolved all major taxa as monophyletic, and Mazocraeidea was split into two major clades: (Diplozoidae) + (all four remaining families: Diclidophoridae, Chauhaneidae, Mazocraeidae and Microcotylidae). It also provided further confirmation that the genus Paradiplozoon is paraphyletic and requires a taxonomic revision, so the two species may have to be renamed Indodiplozoon homoion and Diplozoon yarkandense comb. nov.

Conclusions

Although our findings indicate that mitogenomes may be a promising tool for resolving the phylogeny of Polyopisthocotylea, elevated evolutionary rates of Diplozoidae may cause phylogenetic artefacts, so future studies should pay caution to this problem. Furthermore, as the reason for their elevated evolution remains unknown, Diplozoidae are a remarkably interesting lineage for other types of evolutionary mitogenomic studies.

Graphical Abstract
Congruent responses of vascular plant and ant communities to pastoral land-use abandonment in mountain areas throughout different biogeographic regions
Authors: Verdinelli Marcello , Pittarello Marco , Caria Maria Carmela , Piga Giovanna , Roggero Pier Paolo , Marrosu Gian Marco , Arrizza Stefano , Fadda Maria Leonarda , Lombardi Giampiero , Lonati Michele , Nota Ginevra , Sitzia Maria , Bagella Simonetta
Published: April 2022

Background

There is a long-term trend towards the abandonment of agro-pastoral activities in the mountain areas of Europe: the following encroachment process of semi-natural grasslands by shrubs is one of the main severe threats to the conservation of biodiversity in mountain environments. To better understand the impact of land abandonment, we analysed the reliability of plant functional groups, ant traits, and ant functional groups as indicators of land use changes. We carried out the research in Italy at four sites along a latitudinal/altitudinal gradient in three biogeographic regions (Mediterranean, Continental, Alpine). We identified three stages of a chronosequence at each site as representative of the plant succession in response to pastoral land-use abandonment.

Results

As expected, both the plant and ant assemblages considerably differed across sites at the species level and, within each site, among the three stages. This trend was found also using ant traits, functional groups of ants, and plant functional groups. Ant and plant communities were related in terms of composition and functionality. Harvester ants and ants with collective foraging strategy were associated with annual legumes and grasses (Therophytes); ants with a strictly individual foraging strategy with Phanerophytes. Ant traits and plant functional groups indicated significant differences among the three stages of the chronosequence. However, ant functional groups could not discriminate between the stages represented by secondary grasslands currently grazed and shrub-encroached grasslands ungrazed.

Conclusion

Despite some limitations of ant functional groups in explaining the succession stages of land abandonment, our results suggest that ants are a good surrogate taxon and might be used as bioindicators of land-use changes and ecosystem functioning. Furthermore, our findings indicate that the functional group approach should be applied to other European ecosystems. Finally, reducing the taxonomic complexity could contribute to developing predictive models to detect early environmental changes and biodiversity loss in mountain habitats.
Mindfulness and music interventions in the workplace: assessment of sustained attention and working memory using a crowdsourcing approach
Authors: Axelsen Johanne Lundager , Meline Jacob Stig Jarnot , Staiano Walter , Kirk Ulrich
Published: April 2022

Background

Occupational stress has huge financial as well as human costs. Application of crowdsourcing might be a way to strengthen the investigation of occupational mental health. Therefore, the aim of the study was to assess Danish employees’ stress and cognition by relying on a crowdsourcing approach, as well as investigating the effect of a 30-day mindfulness and music intervention.

Methods

We translated well-validated neuropsychological laboratory- and task-based paradigms into an app-based platform using cognitive games measuring sustained attention and working memory and measuring stress via. Cohen’s Perceived Stress Scale. A total of 623 healthy volunteers from Danish companies participated in the study and were randomized into three groups, which consisted of a 30-day intervention of either mindfulness or music, or a non-intervention control group.

Results

Participants in the mindfulness group showed a significant improvement in the coefficient of sustained attention, working memory capacity and perceived stress (p < .001). The music group showed a 38% decrease of self-perceived stress. The control group showed no difference from pre to post in the survey or cognitive outcome measures. Furthermore, there was a significant correlation between usage of the mindfulness and music app and elevated score on both the cognitive games and the perceived stress scale.

Conclusion

The study supports the nascent field of crowdsourcing by being able to replicate data collected in previous well-controlled laboratory studies from a range of experimental cognitive tasks, making it an effective alternative. It also supports mindfulness as an effective intervention in improving mental health in the workplace.
Test sensitivity in assessing competencies in nursing education
Authors: Wittmann Eveline , Weyland Ulrike , Seeber Susan , Warwas Julia , Striković Aldin , Krebs Philine , Pohley Monja , Wilczek Larissa
Published: April 2022

The identification of effects of vocational education and training conditions on competence development in nursing education requires longitudinal studies. An important precondition is the availability of a test of nursing competence which is economical in use, measures a homogeneous construct throughout years of nursing education and across nursing specializations, and can detect increases in the required competence, hence allowing for sensitive testing. This article describes a cross-sectional study that aimed to optimize a computer-based test measuring nursing competence in care for the elderly—the TEMA test—through the selection of items on the basis of measurement error, differential item functioning, and item difficulty. Evidence of the test sensitivity of the optimized TEMA-L instrument is presented for the second and third year of nursing education. The total sample consisted of n = 133 German nursing students from clinical and geriatric nursing. The resulting instrument includes two test booklets consisting of 36 (WLE = 0.72) and 35 items (WLE = 0.70) respectively for the second and third year of training. The cross-sectional data indicate that the test likely has good properties for sensitive testing of nursing competence in a future longitudinal study. Hence, it might be used to study factors contributing to increases in nursing competence in German VET and serve as an example for similar studies in other countries. Limitations of the current study and related subjects of future research are discussed.
Laparoscopic low anterior resection for rectal cancer associated with Leriche syndrome: a case report
Authors: Nakanishi Ryo , Tsutsui Atsuko , Tanaka Hiroto , Mishima Kohei , Hagiwara Chie , Ozaki Takahiro , Igarashi Kazuharu , Ishii Satoru , Okamoto Nobuhiko , Omura Kenji , Wakabayashi Go
Published: April 2022

A 78-year-old male presented with a positive fecal occult blood test. Rectal cancer was detected during lower gastrointestinal endoscopy, and further investigations led to a diagnosis of cT1N0M0 cStage I (UICC classification, 8th edition). Preoperative contrast-enhanced computed tomography (CT) showed that the patient also had Leriche syndrome, which is associated with reduced blood flow to the rectum that may result in ischemic anastomosis during rectal cancer surgery with anastomotic reconstruction. The inferior epigastric arteries often function as collateral pathways to the lower limbs in patients with Leriche syndrome; therefore, care is needed to avoid vascular damage during trocar insertion when performing laparoscopic surgeries. We herein described a case of safe laparoscopic low anterior resection in a rectal cancer patient with Leriche syndrome using vascular architecture images obtained by preoperative CT angiography.
Protocol for SonoSpeech Cleft Pilot: a mixed-methods pilot randomized control trial of ultrasound visual biofeedback versus standard intervention for children with cleft lip and palate
Authors: Cleland Joanne , Crampin Lisa , Campbell Linsay , Dokovova Marie
Published: April 2022

Background

Children with cleft lip and palate can continue to have problems producing clear speech after surgery. This can lead to social, emotional, and educational challenges. Typical treatment involves teaching children the correct tongue movements to produce speech sounds. This is known as articulation intervention. However, this intervention is challenging because the tongue is hidden from view and movements are difficult to see and describe. This pilot randomized control trial will try a new treatment, ultrasound visual biofeedback (U-VBF) versus standard articulatory intervention for children with cleft lip and palate, as comparison. Feasibility outcomes will be determined.

Methods/design

The Sonospeech project will enroll up to 40 children with cleft lip and palate aged 4;6 to 16 in a mixed-methods randomized controlled trial with blinded assessors. Children will receive either six sessions of U-VBF or articulation intervention. The primary goals of this pilot are to assess the feasibility and inform the design of a full-scale RCT of U-VBF for children with cleft speech characteristics. This will be achieved by determining the following outcome measures: recruitment/attrition rates; measures of pre-post follow-up completion; and acceptability of the randomization and interventions to families.

Discussion

Larger trials of speech interventions for children with cleft lip and palate are needed. This pilot/feasibility study will determine whether a larger randomized control trial comparing ultrasound and articulation interventions is feasible.

Trial registration

ISRCTN, ISRCTN17441953. Registered 22 March 2021. See Table 2 in Appendix 1 for all items.
Feasibility of an educational program for public health nurses to promote local healthcare planning: protocol for a pilot randomized controlled trial
Authors: Yoshioka-Maeda Kyoko , Katayama Takafumi , Shiomi Misa , Hosoya Noriko , Fujii Hitoshi , Mayama Tatsushi
Published: April 2022

Background

Promoting of local healthcare planning is crucial for assisting public health nurses in improving community health inequities. However, there is no effective educational program for developing relevant skills and knowledge among these nurses. Therefore, this study aims to assess the feasibility of a newly developed web-based self-learning program to promote the involvement of public health nurses in the local healthcare planning process.

Methods

A pilot randomized control trial randomly allocated eligible public health nurses to intervention and control wait-list groups [1:1]. The former will be exposed to six web-based learning modules from July to October 2021. After collecting post-test data, the wait-list group will be exposed to the same modules to ensure learning equity. The primary outcome will be evaluated by implementing a validated and standardized scale designed to measure public health policy competencies at the baseline and post-intervention, while secondary outcome will be measured on an action scale to demonstrate the necessity of healthcare activities. The third outcome will be the knowledge and skills related to local healthcare planning by public health nurses. The participants will provide feedback through free descriptions on the trial feasibility and a web-based self-learning program to identify improvement points for continual refinement.

Discussion

The results will provide suggestions in preparation for a future definitive randomized controlled trial. This will provide preliminary data for an intervention aimed at improving relevant competencies among public health nurses who are tasked with resolving health inequities in their respective communities through local health planning.

Trial registration

The protocol for this study was registered with the University Hospital Medical Information Network Clinical Trials Registry and approved by the International Committee of Medical Journal Editors (No. UMIN000043628, March 23, 2021).
5-Aminolevulinic acid antiviral efficacy against SARS-CoV-2 omicron variant in vitro
Authors: Ngwe Tun Mya Myat , Sakura Takaya , Sakurai Yasuteru , Kurosaki Yohei , Inaoka Daniel Ken , Shioda Norifumi , Smith Chris , Yasuda Jiro , Morita Kouichi , Kita Kiyoshi
Published: April 2022

The coronavirus disease 2019 (COVID 19) pandemic continues to pose a threat to global health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has spread rapidly worldwide and became dominant in many countries. A natural 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) has demonstrated antiviral activity in Wuhan, Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 infections in vitro. In this study, we report antiviral activity of 5-ALA, 5-ALA with SFC led to IC50 of 329 and 765/191, respectively after infection with Omicron variant of SARS-CoV-2 in vitro. Our finding suggests that 5-ALA could be used as antiviral drug candidate to treat Omicron variant infected patients.
Effect of 6 weeks of balance training on different heights of medium-density foam in geriatric population
Authors: Kadam Soniya , Pazare Shamla , Iyer Saraswati
Published: April 2022

Background

In older adults, progressive aging leads to a gradual decrease in physical and mental well-being, increasing the risk of fall-associated injuries and ultimately changing the quality of life. This increase in fall accidents is due to the impaired balance in older adults. To prevent such incidents, the incorporation of balance training in the rehabilitation of the geriatric population will help in challenging the vestibular system and activates the mechanoreceptors that lead to enhancing the postural stability on an unstable surface. The foam-based balance training helps to effectively improve balance; however, the height and type of foam used for the treatment and assessment purpose varies, and the suitable height of foam required for balance training is still unexplored. Hence, the study aims to determine the efficacy of various heights of medium-density foam for balance training in community-dwelling older adults.

Methods

Forty older adults ranged between 60 to 75 years were randomly chosen and divided into intervention and control groups. Both the group practiced balance training on a firm surface for 2 weeks and later intervention group received foam-based balance training on either 1″, 2″, and 3″ medium-density foam. The balance and fear of fall were measured using Mini-BesTest Scale (MBS) and Fall Efficacy Scale-I (FES-I) respectively. Furthermore, the MBS and FES-I scores were recorded on the pre-, post-2 weeks, and post-6 weeks of foam-based balance training.

Results

The MBS and FES-I show a statistically significant difference (<0.05) in pre- and post-interventions and control groups. The components of MBS merely show a significant difference in effect size in the intervention group, and it indicates poor clinical relevance in using a specific height of foam for balance training in older adults. However, within group analysis, the 3″-inch medium-density foam shows the medium effect size (>0.5) in all components of MBS as compared to other groups.

Conclusion

The specific height of foam used for foam-based balance training does not effectively differ the clinical decision-making in planning rehabilitation; rather, a long duration of balance training helps to improve balance in older adults.
Impact of CO2 generated from coal-measure source rocks on physical properties of reservoirs — A case study of the Sulige gas field in the Ordos Basin, Northwest China
Authors: Yu Cong , Zhang Bin , Wu Songtao , Hu Guoyi
Published: April 2022

We did have done thermal simulation experiments on coal-measure source rocks, carbon and oxygen isotope analysis of calcite cement in tight sandstone reservoirs, as well as uniform temperature and composition determination of fluid inclusions to illustrate the relationship between the gas generation of coal-measure source rocks and reservoir densification. Coal-measure source rocks produce a considerable amount of CO2 during the entire thermal simulation experiment, especially in the initial stage with the carbon isotope of CO2 ranging from −21.2‰ to −11.6‰, which indicates organic origin. The carbon isotope value of CO2 becomes heavier as the degree of thermal maturation increases. The carbon isotope of calcite cements in the tight sandstone reservoirs of the lower Shihezi Formation is in the range of −13‰ to −4.7‰, which may have the same origin as the CO2 produced during the gas generation of coal-measure source rocks. CO2 derived from coal-measure source rocks can promote the formation of cement, which may be a key reason for the densification of sandstone reservoirs. The fluid inclusions related to oil and gas charging which are mainly methane and carbon dioxide also can confirm this conclusion. At the same time, the CO2 also will impact the dissolution of potash feldspar, albite, and other minerals as well as the reprecipitation of clay minerals, resulting in a more complicated variation of porosity and permeability. CO2 is of great significance in improving oil recovery and the application of carbon capture, utilization, and storage. Studying the influence of CO2 generated from coal-measure source rocks on the physical properties of reservoirs can provide guidance for the mechanism of CO2 storage in the ground.
Distinguishing relapse from antidepressant withdrawal: clinical practice and antidepressant discontinuation studies
Authors: Horowitz Mark Abie , Taylor David
Published: April 2022

We now recognise that withdrawal symptoms from antidepressants are common, and can be severe and long-lasting in some people. Many withdrawal symptoms overlap with symptoms of anxiety or depression, making it difficult to distinguish withdrawal from relapse. We describe how their onset soon after dose reduction, the association of psychological with physical symptoms, their prompt response to reinstatement, and their typical ‘wave’ pattern of onset, peak and resolution can help distinguish withdrawal symptoms from relapse. We also examine evidence that suggests that antidepressant withdrawal symptoms are misdiagnosed as relapse in discontinuation studies aimed at demonstrating the ability of antidepressants to prevent future relapse (relapse prevention properties). In these discontinuation studies people have their antidepressants stopped abruptly, or rapidly, making withdrawal symptoms very likely, and little effort is made to measure withdrawal symptoms or distinguish them from relapse. We conclude that there is currently no robust evidence for the relapse prevention properties of antidepressants, and current guidance might need to be re-evaluated.
Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC)
Authors: Chen Inna M. , Johansen Julia S. , Theile Susann , Hjaltelin Jessica X. , Novitski Sif I. , Brunak Søren , Hasselby Jane P. , Willemoe Gro L. , Lorentzen Torben , Madsen Kasper , Jensen Benny V. , Wilken Eva E. , Geertsen Poul , Behrens Claus , Nolsoe Christian , Hermann Kirstine L. , Svane Inge Marie , Nielsen Dorte
Published: April 2022

PURPOSE

To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC).

METHODS

Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status (ClinicalTrials.gov identifier: NCT02866383 ). The primary end point was the clinical benefit rate (CBR), defined as the percentage of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon's 2-stage phase II optimal design was used independently for both arms, with CBR determining expansion to the second stage. Secondary end points included safety, response rate, duration of response, progression-free survival, and overall survival. Exploratory analyses included biomarkers related to the benefits.

RESULTS

Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (8.0 to 30.6) for patients receiving SBRT/nivolumab and 37.2% (24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient receiving SBRT/nivolumab and lasted for 4.6 months. Six patients receiving SBRT/nivolumab/ipilimumab achieved a PR with a median duration of response of 5.4 months (4.2 to not reached). Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) and 13 (30.2%) patients in the SBRT/nivolumab and SBRT/nivolumab/ipilimumab groups, respectively. Programmed cell death ligand-1 expression by tumor proportion score or combined positivity score of ≥ 1% was not associated with clinical benefits. On-treatment decreased serum interleukin-6, interleukin-8, and C-reactive protein levels were associated with better overall survival.

CONCLUSION

Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory mPC. However, the contribution from SBRT is unknown. Further studies are warranted.
Periodic orbit evaluation of a spectral statistic of quantum graphs without the semiclassical limit
Authors: Harrison J. M. , Hudgins T.
Published: April 2022

Energy level statistics of quantized chaotic systems have been evaluated in the semiclassical limit via their periodic orbits using the Gutzwiller and related trace formulae. Here we evaluate a spectral statistic of chaotic 4-regular quantum graphs from their periodic orbits without the semiclassical limit. The variance of the n-th coefficient of the characteristic polynomial is determined by the sizes of the sets of distinct primitive periodic orbits with n bonds which have no self-intersections, and the sizes of the sets with a given number of self-intersections which all consist of two sections of the pseudo orbit crossing at a single vertex. Using this result we observe the mechanism that connects semiclassical results to the total number of orbits regardless of their structure.
“That Vast Quantity of Laudanum I Have Been Known to Take”
Authors: Breen Benjamin
Published: April 2022

An impostor who claimed to be a refugee from Formosa (present-day Taiwan) named George Psalmanazar (1679?–1763) embodied two key aspects of addiction in eighteenth-century Europe: its connections to globalization and imperialism, and the complex interplay between the concept of “positive” addictions (such as addiction to study, devotion, or duty) and the growing attention paid to “negative” ones (addiction to superstition, sexuality, or intoxicating substances). Constantly changing his identity in response to his audience’s expectations, Psalmanazar lived a life of continual performance—performance that hinged on trading one set of addictions for another. As he abandoned his falsified persona as an opiate-addicted, sexually licentious Taiwanese aristocrat, Psalmanazar embraced a postimposture persona as a pious scholar of religion who, like the holy men he studied, was “addicted to the reading . . . [of] sacred writings.” Strikingly, however, this second life as a humble scholar was sustained by regular opiate use. What had changed was how Psalmanazar thought about his use of the drug: no longer in the service of “vanity” or “extravagance” but instead in the service of God. With their blend of introspection and self-deception, Psalmanazar’s Memoirs (1764) index the changing social and cultural roles of opiates and the concept of addiction in eighteenth-century Europe and beyond.
A Primer for Rebellion
Authors: Chattopadhyaya Utathya
Published: April 2022

This essay explores how the British imperial archive of cannabis addiction in the mid-nineteenth century was shaped by ideas of religious devotion, ordinary leisure, and anxieties arising from revolt and rebellion. It asks how cannabis was discursively constituted as ubiquitous in India and subsequently cast as a conduit to anti-imperial violence in narratives of imperial counterinsurgency. In colonial India, British imperial strategies of knowing the plant’s intoxicating power indexed together several devotional and laboring bodies, among whom the figure of the Indian rebel occupied a unique globally legible location. Revisiting the popular reportage and writing on the Indian Rebellion, this essay argues that cannabis was materialized through the rebel’s body as the rationale for victory, loss, and disorder to ultimately inform and reveal how the reproduction of race and gender shaped the insurgent and counterinsurgent logic of cannabis use under empire.
Ante-Oedipus
Authors: Dillon Elizabeth Maddock
Published: April 2022

This article argues that Freud’s account of binary sexual difference, articulated in the Oedipus complex, is conditioned by a history of racial capitalism. Turning to the foundational work of Hortense Spillers on gender and Atlantic race slavery, this article proposes that dominant models of binary gender are ineluctably racialized, created by the property regimes and systemic sexual violence of colonial modernity that emerged in the Atlantic World of the eighteenth century—a space defined by the structures of labor, race, sexuality, and capital accumulation that developed in and around the first factories of the modern world, namely, the sugar plantations of the colonial Caribbean. The article links Freud’s own economic and intellectual history to the production of capital and the theft of land and labor in the Caribbean by way of the central European trade in textiles and global cotton production. Examining a series of family portraits, the article locates the eclipsed yet central force of Black women’s productive and socially reproductive work extracted for the creation of white, heteropatriarchal reproduction and property accumulation.
In the Interest of History
Authors: Cavitch Max
Published: April 2022

Psychoanalysis is often wrongly perceived to be uninterested in history. Yet, as the most comprehensive and sophisticated basis for the exploration of human consciousness, the field of psychoanalysis, from its inception to the present, has continued to offer unprecedented insights into how we perceive, record, and share the complexities of temporality. The aim of this article is to demonstrate, with the help of various works by Walter Benjamin—works in which his attunement with psychoanalytic concepts is of special interest—that all historical writing must yield, in one way or another, to the post-Freudian description of the unconscious and its role in elaborating historians’ interest in the historical as such.
Paranoid Publics
Authors: Chaudhary Zahid R.
Published: April 2022

This article takes up the recent insurrection in Washington, DC, and the paranoid politics of QAnon. It analyzes the gamification of paranoia across QAnon and related paranoid publics. Taking seriously Sigmund Freud’s insight that delusional formations are attempts at recovery, this article reads QAnon as a part of a symptomatology of the social world.