bluuebunny/crossref_metadata_2025 huggingface dataset:
Bicentre, randomized, parallel-arm, sham-controlled trial of transcranial direct-current stimulation (tDCS) in the treatment of palliative care patients with refractory cancer pain
Authors: Nguyen Jean-Paul , Gaillard Hélène , Suarez Alcira , Terzidis-Mallat Élie , Constant-David Diane , Van Langhenhove Aurélien , Evin Adrien , Malineau Catherine , Tan Son V. O. , Mhalla Alaa , Lefaucheur Jean-Pascal , Nizard Julien
Published: February 2023

Background

Pain is a common symptom in palliative care cancer patients and is often insufficiently relieved. In recent years, transcranial direct-current stimulation (tDCS) of the motor cortex has been shown to be effective to treat chronic pain, essentially neuropathic pain. We propose to test the efficacy of tDCS in patients experiencing cancer pain in the palliative care setting.

Method/design

This article describes the protocol of a bicentre, randomized, parallel-arm, sham-controlled clinical trial evaluating tDCS in the treatment of palliative care patients with refractory cancer pain. Seventy patients between the ages of 18 and 80 years experiencing refractory pain with a pain score of 4/10 on a numerical rating scale (NRS) ranging from 0 to 10 will be enrolled in this trial. The main exclusion criteria are patients unable to fill in the various rating scales and life expectancy less than 3 weeks. Treatment consists of 5 consecutive tDCS sessions targeting the motor cortex (one daily session for 5 days) on the contralateral side to the pain. After randomization (1:1 ratio), 35 patients will receive active stimulation and 35 patients will receive sham stimulation. The primary endpoint is the NRS score and the primary objective is a significant improvement of this score between the baseline score recorded between D-3 and D-1 and the score recorded 4 days after stopping treatment (D8). The secondary objectives are to evaluate whether this improvement is maintained 16 days after stopping treatment (D21) and whether the following scores are improved on D14 and D21: Brief Pain Inventory, Edmonton Symptom Assessment System, Hospital Anxiety and Depression scale, State-Trait Anxiety Inventory and Medication Quantification Scale.

Discussion

Positive results of this trial would indicate that tDCS can improve pain and quality of life of cancer patients in the palliative care setting. Reduction of analgesic consumption and improvement of activities of daily living should allow many patients to return home with a decreased workload for caregivers.
Insights into the structure-function relationship of the NorQ/NorD chaperones from Paracoccus denitrificans reveal shared principles of interacting MoxR AAA+/VWA domain proteins
Authors: Kahle Maximilian , Appelgren Sofia , Elofsson Arne , Carroni Marta , Ädelroth Pia
Published: February 2023

Background

NorQ, a member of the MoxR-class of AAA+ ATPases, and NorD, a protein containing a Von Willebrand Factor Type A (VWA) domain, are essential for non-heme iron (FeB) cofactor insertion into cytochrome c-dependent nitric oxide reductase (cNOR). cNOR catalyzes NO reduction, a key step of bacterial denitrification. This work aimed at elucidating the specific mechanism of NorQD-catalyzed FeB insertion, and the general mechanism of the MoxR/VWA interacting protein families.

Results

We show that NorQ-catalyzed ATP hydrolysis, an intact VWA domain in NorD, and specific surface carboxylates on cNOR are all features required for cNOR activation. Supported by BN-PAGE, low-resolution cryo-EM structures of NorQ and the NorQD complex show that NorQ forms a circular hexamer with a monomer of NorD binding both to the side and to the central pore of the NorQ ring. Guided by AlphaFold predictions, we assign the density that “plugs” the NorQ ring pore to the VWA domain of NorD with a protruding “finger” inserting through the pore and suggest this binding mode to be general for MoxR/VWA couples.

Conclusions

Based on our results, we present a tentative model for the mechanism of NorQD-catalyzed cNOR remodeling and suggest many of its features to be applicable to the whole MoxR/VWA family.
Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
Authors: Rothwell Joseph A. , Bešević Jelena , Dimou Niki , Breeur Marie , Murphy Neil , Jenab Mazda , Wedekind Roland , Viallon Vivian , Ferrari Pietro , Achaintre David , Gicquiau Audrey , Rinaldi Sabina , Scalbert Augustin , Huybrechts Inge , Prehn Cornelia , Adamski Jerzy , Cross Amanda J. , Keun Hector , Chadeau-Hyam Marc , Boutron-Ruault Marie-Christine , Overvad Kim , Dahm Christina C. , Nøst Therese Haugdahl , Sandanger Torkjel M. , Skeie Guri , Zamora-Ros Raul , Tsilidis Kostas K. , Eichelmann Fabian , Schulze Matthias B. , van Guelpen Bethany , Vidman Linda , Sánchez Maria-José , Amiano Pilar , Ardanaz Eva , Smith-Byrne Karl , Travis Ruth , Katzke Verena , Kaaks Rudolf , Derksen Jeroen W. G. , Colorado-Yohar Sandra , Tumino Rosario , Bueno-de-Mesquita Bas , Vineis Paolo , Palli Domenico , Pasanisi Fabrizio , Eriksen Anne Kirstine , Tjønneland Anne , Severi Gianluca , Gunter Marc J.
Published: February 2023

Background

Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts.

Methods

Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases.

Results

Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded.

Conclusions

Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
Systemic inflammation indicators and risk of incident arrhythmias in 478,524 individuals: evidence from the UK Biobank cohort
Authors: Yang Xiaorong , Zhao Shaohua , Wang Shaohua , Cao Xuelei , Xu Yue , Yan Meichen , Pang Mingmin , Yi Fan , Wang Hao
Published: February 2023

Background

The role of systemic inflammation in promoting cardiovascular diseases has attracted attention, but its correlation with various arrhythmias remains to be clarified. We aimed to comprehensively assess the association between various indicators of systemic inflammation and atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia in the UK Biobank cohort.

Methods

After excluding ineligible participants, a total of 478,524 eligible individuals (46.75% male, aged 40–69 years) were enrolled in the study to assess the association between systemic inflammatory indicators and each type of arrhythmia.

Results

After covariates were fully adjusted, CRP levels were found to have an essentially linear positive correlation with the risk of various arrhythmias; neutrophil count, monocyte count, and NLR showed a non-linear positive correlation; and lymphocyte count, SII, PLR, and LMR showed a U-shaped association. VA showed the strongest association with systemic inflammation indicators, and it was followed sequentially by AF and bradyarrhythmia.

Conclusions

Multiple systemic inflammatory indicators showed strong associations with the onset of AF, VA, and bradyarrhythmia, of which the latter two have been rarely studied. Active systemic inflammation management might have favorable effects in reducing the arrhythmia burden and further randomized controlled studies are needed.
Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 5. Mortality assessment
Authors: Perry Henry B. , Stollak Ira , Llanque Ramiro , Okari Annah , Westgate Carey C. , Shindhelm Alexis , Chou Victoria B. , Valdez Mario
Published: February 2023

Background

The Curamericas/Guatemala Maternal and Child Health Project, 2011–2015, implemented the Census-Based, Impact-Oriented Approach, the Care Group Approach, and the Community Birthing Center Approach. Together, this expanded set of approaches is known as CBIO+. This is the fifth of 10 papers in our supplement describing the Project and the effectiveness of the CBIO+ Approach. This paper assesses causes, levels, and risk factors for mortality along with changes in mortality.

Methods

The Project maintained Vital Events Registers and conducted verbal autopsies for all deaths of women of reproductive age and under-5 children. Mortality rates and causes of death were derived from these data. To increase the robustness of our findings, we also indirectly estimated mortality decline using the Lives Saved Tool (LiST).

Findings

The leading causes of maternal and under-5 mortality were postpartum hemorrhage and pneumonia, respectively. Home births were associated with an eight-fold increased risk of both maternal (p = 0.01) and neonatal (p = 0.00) mortality. The analysis of vital events data indicated that maternal mortality declined from 632 deaths per 100,000 live births in Years 1 and 2 to 257 deaths per 100,000 live birth in Years 3 and 4, a decline of 59.1%. The vital events data revealed no observable decline in neonatal or under-5 mortality. However, the 12–59-month mortality rate declined from 9 deaths per 1000 live births in the first three years of the Project to 2 deaths per 1000 live births in the final year. The LiST model estimated a net decline of 12, 5, and 22% for maternal, neonatal and under-5 mortality, respectively.

Conclusion

The baseline maternal mortality ratio is one of the highest in the Western hemisphere. There is strong evidence of a decline in maternal mortality in the Project Area. The evidence of a decline in neonatal and under-5 mortality is less robust. Childhood pneumonia and neonatal conditions were the leading causes of under-5 mortality. Expanding access to evidence-based community-based interventions for (1) prevention of postpartum hemorrhage, (2) home-based neonatal care, and (3) management of childhood pneumonia could help further reduce mortality in the Project Area and in similar areas of Guatemala and beyond.
Reducing inequities in maternal and child health in rural Guatemala through the CBIO+﻿ Approach of Curamericas: 10. Summary, cost effectiveness, and policy implications
Authors: Perry Henry B. , Stollak Ira , Valdez Mario
Published: February 2023

Background

This is the final of 10 papers that describe the implementation of the Expanded Census-Based, Impact-Oriented Approach (CBIO+) by Curamericas/Guatemala in the Cuchumatanes mountains of the Department of Huehuetenango and its effectiveness in improving the health and well-being of women and children in a population of 98,000 in three municipalities. The CBIO+ Approach consists of three components: the CBIO (Census-Based, Impact-Oriented) Approach, the Care Group Approach, and the Community Birthing Center Approach.

Methods

Each of the preceding papers was summarized. An assessment was made regarding the degree to which the initial implementation research hypotheses were confirmed. The total field cost per capita for operation of the Project was calculated. An assessment of the cost-effectiveness of the Project was made based on the estimated impact of the Project, the number of lives saved, and the number of disability-adjusted life years averted.

Results

The Project attained a number of notable achievements in terms of expanding the coverage of key maternal and child health interventions, improving the nutritional status of children, reducing the mortality of children and mothers, providing quality care for mothers at the Community Birthing Centers (Casas Maternas Rurales) that integrate traditional midwives (comadronas) into the care of women during childbirth at the birthing centers, as well as empowering women and building social capital in the communities. CBIO+ is an effective and affordable approach that is particularly notable for its capacity to engage communities in the process of improving the health of mothers and children. Overall, there is strong and consistent evidence in support of the research hypotheses. The findings did produce evidence of declines in under-5 and maternal mortality, but they were not as robust as had been hoped.

Conclusion

CBIO+ is an approach that has been effective in engaging communities in the process of improving the health of their mothers and children and in reducing health inequities in this marginalized, difficult-to-reach population of Indigenous Maya people. The CBIO+ Approach is cost-effective and merits further development and broader application in Guatemala and beyond.
Assessing the patient experience of respiratory syncytial virus infection: development of a patient-reported outcome measure
Authors: Romano Carla , Finelli Lyn , Lewis Sandy , Williams Valerie , Martin Emily , Phillips Matthew , Saretsky Todd L. , Norquist Josephine
Published: February 2023

Background

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in older adults. Despite a number of RSV vaccine candidates in clinical trials, there are no existing disease-specific, self-reported measures that assess the symptoms and severity of RSV infection from the perspective of adult patients with acute RSV. The objective of this study was to describe the initial conceptualization and development of the RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ), a new patient-reported outcome measure.

Methods

A targeted review of the literature identified relevant existing measures, symptoms, and impacts of RSV. A draft version of the RSV-iiiQ was developed based on the Influenza Intensity and Impact Questionnaire (Flu-iiQ) with expert input. Qualitative interviews (N = 20) were conducted with participants to optimize the RSV-iiiQ conceptual model and confirm the content validity of the RSV-iiiQ. Interviews included concept elicitation and a cognitive debriefing assessment. A draft conceptual framework was developed, and the electronic clinical outcome assessment was piloted. All steps of instrument development followed Food and Drug Administration guidance for patient-reported outcomes.

Results

In-depth concept elicitation interviews followed by cognitive debriefings demonstrated that the content of the items was comprehensive, covered the breadth of RSV symptoms and impacts, and was relevant to the experiences of individuals with RSV. Both the paper and electronic versions of the RSV-iiiQ were easily completed. Minor refinements were made to some items based on participant feedback, and the draft conceptual framework was refined.

Conclusions

The RSV-iiiQ was developed for use in clinical trials to measure the symptom intensity and impact of acute RSV infection from the perspective of adult patients. The tool was developed in accordance with current regulatory guidance and is useful to support patient-focused drug development.
Regional anesthesia did not improve postoperative long-term survival of tumor patients: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Tao , Meng Xiangrui , Wang Di , Wang Qiang , Ma Jiahai , Dai Zhao
Published: February 2023

Objective

Experimental research and clinical trials have reported a positive effect of regional anesthesia (RA) on prognosis of cancers. We systematically reviewed the efficacy of RA on recurrence-free survival (RFS) and overall survival (OS) after oncology surgeries.

Methods

PubMed, Cochrane library, and Embase were searched from inception to June 20, 2022 for RCTs in which any form of RA was initiated perioperatively. Time-to-event data (hazard ratio (HR)) were extracted independently and in duplicate. The primary outcome was the association of RA with RFS and OS, while the secondary outcomes included time to tumor progression, 5-year RFS, and 5-year OS.

Results

Fifteen RCTs with 5981 participants were included. Compared to GA, RA has no positive effect on RFS (HR, − 0.02; 95% CI, − 0.11 to 0.07), OS (HR, − 0.03; 95% CI, − 0.28 to 0.23), time to tumor progression (0.11; 95% CI, − 0.33 to 0.55), 5-year RFS (risk ratio (RR), 1.24; 95% CI, 0.88 to 1.76)), and 5-year OS (RR, 1.11; 95% CI, 0.85 to 1.44). Subgroup analysis based on study design, patient characteristics and tumor types also showed no effect of RA on RFS or OS.

Conclusions

Our results demonstrated that there is no significant evidence supporting the role of RA in improving long-term survival after oncology surgeries.
Automating iPSC generation to enable autologous photoreceptor cell replacement therapy
Authors: Bohrer Laura R. , Stone Nicholas E. , Mullin Nathaniel K. , Voigt Andrew P. , Anfinson Kristin R. , Fick Jessica L. , Luangphakdy Viviane , Hittle Bradley , Powell Kimerly , Muschler George F. , Mullins Robert F. , Stone Edwin M. , Tucker Budd A.
Published: February 2023

Background

Inherited retinal degeneration is a leading cause of incurable vision loss in the developed world. While autologous iPSC mediated photoreceptor cell replacement is theoretically possible, the lack of commercially available technologies designed to enable high throughput parallel production of patient specific therapeutics has hindered clinical translation.

Methods

In this study, we describe the use of the Cell X precision robotic cell culture platform to enable parallel production of clinical grade patient specific iPSCs. The Cell X is housed within an ISO Class 5 cGMP compliant closed aseptic isolator (Biospherix XVivo X2), where all procedures from fibroblast culture to iPSC generation, clonal expansion and retinal differentiation were performed.

Results

Patient iPSCs generated using the Cell X platform were determined to be pluripotent via score card analysis and genetically stable via karyotyping. As determined via immunostaining and confocal microscopy, iPSCs generated using the Cell X platform gave rise to retinal organoids that were indistinguishable from organoids derived from manually generated iPSCs. In addition, at 120 days post-differentiation, single-cell RNA sequencing analysis revealed that cells generated using the Cell X platform were comparable to those generated under manual conditions in a separate laboratory.

Conclusion

We have successfully developed a robotic iPSC generation platform and standard operating procedures for production of high-quality photoreceptor precursor cells that are compatible with current good manufacturing practices. This system will enable clinical grade production of iPSCs for autologous retinal cell replacement.
Caprin-1 plays a role in cell proliferation and Warburg metabolism of esophageal carcinoma by regulating METTL3 and WTAP
Authors: Gao Yan , Yuan Lingling , Ke Changbin , Pei Zhijun , Liu Xiaobo , Wu Ruimin , Kui Xueyan , Zhang Yanmin
Published: February 2023

Background

Cytoplasmic activation/proliferation-associated protein-1 (Caprin-1) is implicated in cancer cell proliferation and tumorigenesis; however, its role in the development of esophageal carcinoma (ESCA) has not been examined.

Methods

Biological methods and data analysis were used to investigate the expression of Caprin-1 in ESCA tissue and cell lines. We comprehensively analyzed the mRNA expression and prognostic values, signalling pathways of CAPRIN1 in ESCA using public databases online. Biological functions of CAPRIN1 were performed by clorimetric growth assay, EdU staining, colony formation, flow cytometry, apoptosis analysis, Western blot, lactate detection assay, extracellular acidification rates. The underlying mechanism was determined via flow cytometric analysis, Western blot and rescue experiments. In addition, xenograft tumor model was constructed to verify the phenotypes upon CAPRIN1 silencing.

Results

Caprin-1 expression was significantly elevated in both ESCA tumor tissues and cell lines compared with that in normal adjacent tissues and fibroblasts. Increased CAPRIN1 mRNA expression was significantly associated with clinical prognosis and diagnostic accuracy. The GO enrichment and KEGG pathway analysis CAPRIN1 might be related to immune-related terms, protein binding processes, and metabolic pathways. A significant positive correlation was observed between high Caprin-1 protein levels and lymph node metastasis (P = 0.031), ki-67 (P = 0.023), and 18F- FDG PET/CT parameters (SUVmax (P = 0.002) and SUV mean (P = 0.005)) in 55 ESCA patients. At cut-off values of SUVmax 17.71 and SUVmean 10.14, 18F- FDG PET/CT imaging predicted Caprin-1 expression in ESCA samples with 70.8% sensitivity and 77.4% specificity. In vitro and in vivo assays showed that Caprin-1 knockdown affected ESCA tumor growth. Silencing Caprin-1 inhibited ESCA cell proliferation and glycolysis, and decreased the expression of methyltransferase-like 3 (METTL3) and Wilms’ tumor 1-associating protein (WTAP). However, this effect could be partially reversed by the restoration of METTL3 and WTAP expression.

Conclusions

Our data suggest that Caprin-1 could serve as a prognostic biomarker and has an oncogenic role in ESCA.
Nanoscale, antigen encounter-dependent, IL-12 delivery by CAR T cells plus PD-L1 blockade for cancer treatment
Authors: Yang Zhifen , Pietrobon Violena , Bobbin Maggie , Stefanson Ofir , Yang Jin , Goswami Angshumala , Alphson Bennett , Choi Hana , Magallanes Khristina , Cai Qi , Barrett David , Wang Bing , Qi Lei S. , Marincola Francesco M.
Published: February 2023

Background

Chimeric antigen receptor (CAR)-T cell therapies for the treatment of hematological malignancies experienced tremendous progress in the last decade. However, essential limitations need to be addressed to further improve efficacy and reduce toxicity to assure CAR-T cell persistence, trafficking to the tumor site, resistance to an hostile tumor microenvironment (TME), and containment of toxicity restricting production of powerful but potentially toxic bioproducts to the TME; the last could be achieved through contextual release upon tumor antigen encounter of factors capable of converting an immune suppressive TME into one conducive to immune rejection.

Methods

We created an HER2-targeting CAR-T (RB-312) using a clustered regularly interspaced short palindromic repeats (CRISPR) activation (CRISPRa) system, which induces the expression of the IL-12 heterodimer via conditional transcription of its two endogenous subunits p35 and p40. This circuit includes two lentiviral constructs. The first one (HER2-TEV) expresses an anti-human epidermal growth factor receptor 2 (HER2) CAR single chain variable fragment (scFv), with CD28 and CD3z co-stimulatory domains linked to the tobacco etch virus (TEV) protease and two single guide RNAs (sgRNA) targeting the interleukin (IL)-12A and IL12B transcription start site (TSS), respectively. The second construct (LdCV) encodes linker for activation of T cells (LAT) fused to nuclease-deactivated Streptococcus Pyogenes Cas9 (dCas9)-VP64-p65-Rta (VPR) via a TEV-cleavable sequence (TCS). Activation of the CAR brings HER2-TEV in close proximity to LdCV releasing dCas9 for nuclear localization. This conditional circuit leads to conditional and reversible induction of the IL-12/p70 heterodimer. RB-312 was compared in vitro to controls (cRB-312), lacking the IL-12 sgRNAs and conventional HER2 CAR (convCAR).

Results

The inducible CRISPRa system activated endogenous IL-12 expression resulting in enhanced secondary interferon (FN)-γ production, cytotoxicity, and CAR-T proliferation in vitro, prolonged in vivo persistence and greater suppression of HER2+ FaDu oropharyngeal cancer cell growth compared to the conventional CAR-T cell product. No systemic IL-12 was detected in the peripheral circulation. Moreover, the combination with programmed death ligand (PD-L1) blockade demonstrated robust synergistic effects.

Conclusions

RB-312, the first clinically relevant product incorporating a CRISPRa system with non-gene editing and reversible upregulation of endogenous gene expression that promotes CAR-T cells persistence and effectiveness against HER2-expressing tumors. The autocrine effects of reversible, nanoscale IL-12 production limits the risk of off-tumor leakage and systemic toxicity.
Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs): study protocol for a neural and molecular mechanistic clinical trial
Authors: Walsh Melissa J. M. , Gibson Kathryn , Hynd Megan , Eisenlohr-Moul Tory A. , Walsh Erin C. , Schiff Lauren , Jarskog Fred , Lalush David , Dichter Gabriel S. , Schiller Crystal E.
Published: February 2023

Background

The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis.

Methods

This study will recruit 100 unmedicated women ages 44–55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith–Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment.

Discussion

This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction.

Trial registration

ClinicalTrials.gov NCT05282277
Distant genetic variants of Anaplasma phagocytophilum from Ixodes ricinus attached to people
Authors: Lesiczka Paulina Maria , Hrazdilova Kristyna , Hönig Václav , Modrý David , Zurek Ludek
Published: February 2023

Background

Although the tick-borne pathogen Anaplasma phagocytophilum is currently described as a single species, studies using genetic markers can distinguish groups of variants associated with different hosts, pathogenicity, zoonotic potential and biotic and geographic niches. The objective of our study was to investigate the genetic diversity of A. phagocytophilum and Ixodes ricinus ticks attached to people.

Methods

In collaboration with a commercial diagnostic company, a total of 52 DNA samples were obtained from ticks that tested positive for A. phagocytophilum by quantitative PCR. The genetic profile of each sample was determined using the groEL and ankA genes. Identification of the tick species was confirmed by partial sequencing of the COI subunit and a portion of the TROSPA gene.

Results

All 52 ticks were identified as I. ricinus. Two protocols of nested PCR amplifying 1293- and 407-bp fragments of groEL of A. phagocytophilum yielded amplicons of the expected size for all 52 samples. Among all sequences, we identified 10 unique genetic variants of groEL belonging to ecotype I and ecotype II. The analysis targeting ankA was successful in 46 of 52 ticks. Among all sequences, we identified 21 unique genetic variants phylogenetically belonging to three clusters.

Conclusions

Our results indicate that ticks attached to people harbor distant genetic variants of A. phagocytophilum, some of which are not recognized as zoonotic. Further studies are needed to determine the risk of human infection by genetic variants other than those designated as zoonotic.

Graphical Abstract
Calculated and measured radiation dose for the low energy xoft axxent eBT X-ray source
Authors: Can Sümeyra , Atilla Özge , Karaçetin Didem
Published: February 2023

Purpose

In this study, it was aimed to evaluate the functionality to deliver different prescription dose except 20 Gy for the Xoft Axxent Ebt (electronic Brachytherapy) system and analyzing the system in terms of radiation dosimetry in water and 0.9% isotonic Sodium Chloride (NaCl) solution.

Materials and methods

In the Xoft Axxent eBT, different prescription dose in single fraction were calculated for different balloon applicator volumes based on source position and irradiation times. EBT-XD Gafchromic film was calibrated at 6MV photon energy. A balloon applicator filled with 0.9% isotonic NaCl solution was used to deliver a radiation dose of 20 Gy, 16 Gy, 10 Gy on the applicator surface. Then the balloon applicator was filled with water and the same measurements were repeated. Finally, the balloon applicator was irradiated by positioning it at different distances in the water phantom to simulate the isodose contour.

Results

At the time the balloon applicator was filled with water and 0,9% NaCl solution, the difference between the planned dose and the absorbed dose was ~ 2% vs. 15% for 30 cc, ~ 5% vs. 14% for 35 cc and ~ 3,5% vs. 10% for 40 cc respectively. Finally, the absorbed dose at a distance of 1 cm from the applicator surface was measured as 9.63 Gy.

Conclusion

In this study, it was showed that different prescription dose could be possible to deliver in the Xoft Axxent eBT system based on the standard plan. In addition, the absorbed dose was higher than the planned dose depending on the effective atomic number of NaCl solution comparing to water due to photoelectric effect in low energy photons. By measuring the dose distributions at different distances from the balloon applicator surface, the absorbed dose in tissue equivalent medium was determined and the isodose contours characteristics was simulated.
Psychometric properties of the arabic version of the positive/negative experiences of parents for school-aged students about online learning during COVID-19 pandemic assessment scale
Authors: Bajamal Eman , Anazi Samaa Al , Esheaba Ola , Hantira Neama
Published: February 2023

Background

The current literature examining the impact of online learning on parents and their children, specifically in the time of COVID-19 are still lacking in Saudi Arabia. Therefore, the aim of the study to evaluate the psychometric properties of the Arabic version of the positive/negative experiences of online learning during COVID-19 Pandemic Assessment Scale.

Methods

A cross-sectional study approved by a university institutional review board was conducted among 184 participants in 2021. The scale was translated from English into Arabic and culturally adapted as needed. The psychometric properties of the instruments, including face and content validity, and internal consistency were evaluated. Exploratory factor analysis (EFA) was conducted to cross-validate the factor structure. The Spearman’s Rho Correlation was used to assess convergent validity.

Results

Cronbach’s alpha were 0.890 and 0.892, respectively, indicating acceptable internal consistency. Item-total correlation coefficients ranged from 0.52 to 0.73 and 0.43 to 0.76, respectively. The EFA indicated a single-factor with a total% variance 52.89 for the positive experience items of the scale and 56.83 for the negative experience items of the scale.

Conclusion

The Arabic version of the the positive/negative experiences of online learning during COVID-19 Pandemic Assessment Scale is reliable and valid measure for assessing parents experiences among Arabic-speaking population.
Macrocell Corrosion Currents in Simulated Concrete Pore Solution and Reinforced Concrete
Authors: Lliso-Ferrando Josep Ramon , Gasch Isabel , Martínez-Ibernón Ana , Valcuende Manuel
Published: February 2023

Chloride-induced rebar corrosion is one of the main causes of damage in reinforced concrete structures (RCS). Chloride attacks lead to depassivation creating pits, which can imply major losses of sections. The current generated at these spots (microcell) is contributed by the current produced between corroded and uncorroded areas (macrocell). The influence of both currents has been deeply investigated based on solution studies, which do not actually represent the behaviour of concrete-embedded elements. The studies about macrocell currents in solution are interesting to analyse this phenomenon quickly and simply. However, they must not be interpreted as the reality of RCS because this requires studies using rebars embedded in concrete. The performed experimental plan verified this fact. In addition, another objective of this study was to analyse the influence of concrete’s electrical resistance and the limiting effect of the cathode/anode surface (Cs/As) ratio on macrocell currents in solution and in concrete. For this study, specimens manufactured using concretes with different properties were used: standard concrete (SC), high-performance concrete (HPC), very high-performance concrete (VHPC) and ultra-high performance-fibre reinforced concrete (UHPFRC). The conclusions show how the Cs/As ratio plays a key role in regulating macrocell current intensity, but what really governs this phenomenon is concrete resistivity because it regulates the participation of a bigger or smaller cathode surface. The influence of this parameter as a limiting factor of macrocell currents is fundamental, especially in high resistivity concretes like VHPC and UHPFRC.
Accidental retropharyngeal dissection extending close to the right common carotid artery during nasotracheal intubation: a case report
Authors: Okamoto Aki , Kawaraguchi Yoshitaka , Fujita Masahide , Goto Yasunobu , Shimokawa Mitsuru
Published: February 2023

Background

Retropharyngeal dissection is a possible complication during nasotracheal intubation. We report a case of a retropharyngeal dissection extending close to the right common carotid artery occurring while inserting a nasotracheal tube.

Case presentation

An 81-year-old woman, scheduled for laparoscopic and endoscopic cooperative surgery for a duodenal tumor under general anesthesia, sustained submucosal dissection of the retropharyngeal space during nasotracheal intubation. Postoperative computed tomography revealed retropharyngeal tissue injury extending close to the right common carotid artery. The patient was treated with prophylactic antibiotic therapy and discharged uneventfully on postoperative day 13.

Conclusions

Submucosal dissection of the retropharyngeal tissue during nasotracheal intubation has a potential risk of major cervical vessel injury. Therefore, when the tip of the tube cannot be visualized within the oropharynx, clinicians must proceed with caution regarding the expected depth of the tube.
Pathogenicity of entomopathogenic nematodes against the new invasive fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae)
Authors: Mohamed Hend O. , Shairra Souad A.
Published: February 2023

Background

Fall armyworm (FAW), Spodopterafrugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is the new invasive pest of different economic crops, threatening the agricultural economy worldwide. Chemical insecticides are the main control management strategy applied by almost farmers. As the adverse effect of these chemicals on the environment and human health, improving alternative environmentally friendly control against this pest is urgently needed. In this response, the pathogenicity bioassays of 2 entomopathogenic nematode species (EPNs), Steinernemacarpocapsae (All) and Heterorhabditisindica (EGAZ2), on different FAW larval instars (2nd to 6th instars) were assessed under laboratory conditions.

Results

The results cleared that FAW larval mortality rate was varied significantly related to nematode species, post-exposure times and developmental instar stages. S.carpocapsae application was more virulent and effective against all tested instars larvae, registering 100% mortality after 48–72 h post-exposure at different nematode concentrations (150–2400 IJs). However, H.indica caused 100% mortality in early instars only after 96 h, but late instars required a longer time extending to 120–188 h at tested concentrations. In this context, 2nd and 3rd instars were highly susceptible to Heterorhabditis species infection. Lower nematode concentrations (150–300 IJs) caused moderate mortality 33.33–50%, respectively, in 5th and 6th full-developed larvae only. All recovery larvae post-infection died in the pupal stage or adult emerged with wing malformation.

Conclusion

The 2 EPN species were virulent against different FAW larval instars at different concentrations and exposure times. Thereby, they are recommended as biocontrol agents against this invasive pest, particularly S.carpocapsae after low-exposure time. This study provides essential information on EPNs, which will further help in the practical application of biological control against fall armyworm.
Foot and mouth disease in Ethiopia: a systematic review and meta-analysis in the last fifteen years (2007–2021)
Authors: Seyoum Wasihun , Tora Ephrem
Published: February 2023

Background

Foot and Mouth disease (FMD) is an acute contagious and highly infectious disease of domesticated and wild cloven-hoofed animals characterized by the appearance of vesicular lesions at the epithelium of the mouth, nares, muzzle, feet and udder, causing repeated outbreaks every year in Ethiopia, thereby causing production loss and the banning of exportation of livestock, products and their by-products. The prevalence of foot and mouth disease in Ethiopia has been reported from different parts of the country, but a pooled quantitative estimate of foot and mouth disease has not been done so far; therefore this meta-analysis sought to determine FMD status in Ethiopia.

Main body

Literature search was conducted by the main search engines and indexing services: Google, Google Scholar, PubMed, and Science Direct. Additionally, university repositories were discovered to retrieve unpublished MSc theses. All studies dealt with the prevalence of FMD. Raw data were extracted in Microsoft Excel and then imported into R Studio. Random effects model was used to pool estimates of outcomes at 95% confidence interval. Heterogeneity level was computed by Higgins’s I2 statistics. Publication bias was checked using funnel plots for standard error augmented by Begg’s and Egger’s tests. In total, 27 reports with 13,510 cattle were included in this study. An estimate of prevalence across reviews for the entire literature collected from the period 2007 to 2021 was 21.39% (16.53–26.56). Sub-analysis for herd size, animal composition, age group and sex of cattle identified as potential significant factors for FMD. FMD prevalence in cattle at early age and adult age was 19.5% and 14.6%, respectively (P < 0.01). Compared to intensive production, FMD occurrence was 4.3 times higher in extensive production (P value = 0.003).

Conclusions

FMD is prevalent in Ethiopian cattle, and the disease is a list A disease which could affect the export of live animals and their products since FMD is a trans-boundary disease. Therefore, it is imperative to have strategic implementation of effective prevention, control, and robust eradication policies.
Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis
Authors: Muntané Gerard , Vázquez-Bourgon Javier , Sada Ester , Martorell Lourdes , Papiol Sergi , Bosch Elena , Navarro Arcadi , Crespo-Facorro Benedicto , Vilella Elisabet
Published: February 2023

Background

Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with a reduction in general physical health. Although genetics is assumed to be a significant contributor to weight gain, its exact role is unknown.

Methods

We assembled a population-based FEP cohort of 381 individuals that was split into a Training (n = 224) set and a Validation (n = 157) set to calculate the polygenic risk score (PRS) in a two-step process. In parallel, we obtained reference genome-wide association studies for body mass index (BMI) and schizophrenia (SCZ) to examine the pleiotropic landscape between the two traits. BMI PRSs were added to linear models that included sociodemographic and clinical variables to predict BMI increase (∆BMI) in the Validation set.

Results

The results confirmed considerable shared genetic susceptibility for the two traits involving 449 near-independent genomic loci. The inclusion of BMI PRSs significantly improved the prediction of ∆BMI at 12 months after the onset of antipsychotic treatment by 49.4% compared to a clinical model. In addition, we demonstrated that the PRS containing pleiotropic information between BMI and SCZ predicted ∆BMI better at 3 (12.2%) and 12 months (53.2%).

Conclusions

We prove for the first time that genetic factors play a key role in determining ∆BMI during the FEP. This finding has important clinical implications for the early identification of individuals most vulnerable to weight gain and highlights the importance of examining genetic pleiotropy in the context of medically important comorbidities for predicting future outcomes.
Diagnostic and Treatment Strategies for AL Amyloidosis in an Era of Therapeutic Innovation
Authors: Dima Danai , Mazzoni Sandra , Anwer Faiz , Khouri Jack , Samaras Christy , Valent Jason , Williams Louis
Published: February 2023

Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for clinicians across practice settings. There is, however, a reason for optimism with the advent of new combination therapy approaches and novel targets offering the promise of improvement in end organ function, survival, and quality of life. This review offers a clinically applicable overview of an approach to diagnosis, risk stratification, and clinical management of AL amyloidosis in an era of rapid therapeutic innovation.
Topological defects in silicene
Authors: Kosarev I. V. , Kistanov A. A. , Babicheva R. I. , Korznikova E. A. , Baimova J. A. , Dmitriev S. V.
Published: February 2023

Using the molecular dynamic simulations a new class of topological defects in silicene is investigated. Si atoms in silicene belong to two triangular sublattices shifted one with respect to the other by h along the direction normal to the sheet. Silicene can have two energetically equivalent structures when the first or second sublattice is above the other. Topological defects appear at the junctions of the domains of these two structures. Domain walls can be rectilinear or curvilinear. Such defects cannot disappear from the structure except as a result of the annihilation of defects with positive and negative topological charges. Structure and energy of the topological defects are calculated. The effect of temperature is shown. Similar defects inevitably exist in other group IVA elemental 2D materials with buckled structure, such as germanene, stanene, and plumbene. As a result of the work, the problem of experimental detection of such defects and the question of how they affect the physicochemical and mechanical properties of materials, in particular, toxicity or sensory properties, is posed.
Waste Works
Authors: Chalfin Brenda
Published: February 2023

In Waste Works, Brenda Chalfin examines Ghana’s planned city of Tema, theorizing about the formative role of waste infrastructure in urban politics and public life. Chalfin argues that at Tema’s midcentury founding, a prime objective of governing authorities was to cultivate self-contained citizens by means of tightly orchestrated domestic infrastructure and centralized control of bodily excrement to both develop and depoliticize the new nation. Comparing infrastructural innovations across the city, Chalfin excavates how Tema residents pursue novel approaches to urban waste and sanitation built on the ruins of the inherited order, profoundly altering the urban public sphere. Once decreed a private matter to be guaranteed by state authorities, excrement becomes a public issue, collectively managed by private persons. Pushing self-care into public space and extending domestic responsibility for public well-being and bodily outputs, popularly devised waste infrastructures are a decisive arena to make claims, build coalitions, and cultivate status. Confounding high-modernist ideals, excremental infrastructures unlock bodily waste’s diverse political potentials.