bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomics of the midgut microbiome of Rhipicephalus microplus from China
Authors: Zhang Xue-Ling , Deng Yuan-Ping , Yang Tian , Li Le-Yan , Cheng Tian-Yin , Liu Guo-Hua , Duan De-Yong
Published: February 2022

Background

Ticks, which are ectoparasites of animals, may carry multiple pathogens. The cattle tick Rhipicephalus microplus is an important bovine parasite in China. However, the midgut microbiome of R. microplus from China has not been characterized via metagenomic methods.

Methods

Rhipicephalus microplus were collected from cattle in the city of Changsha in Hunan province, China. The DNA of the midgut contents was extracted from fully engorged adult female R. microplus. A DNA library was constructed and sequenced using an Illumina HiSeq sequencing platform. SOAPdenovo software was used to assemble and analyze the clean data. The latent class analysis algorithm applied to system classification by MEGAN software was used to annotate the information on the species’ sequences. DIAMOND software was used to compare unigenes with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and functional annotation was carried out based on the results of the comparison.

Results

The dominant phyla in the five samples were Firmicutes, Proteobacteria, and Actinobacteria. Streptococcus, Mycobacterium, Anaplasma, Enterococcus, Shigella, Lactobacillus, Brachyspira, Pseudomonas, Enterobacter, Bacillus, and Lactococcus were the dominant genera in the five samples. The endosymbiotic bacterium Wolbachia was also detected in all of the samples. Mycobacterium malmesburyense, Streptococcus pneumoniae, Anaplasma phagocytophilum, Enterococcus faecium, Shigella sonnei, Enterococcus faecalis, Lactobacillus casei, Brachyspira hampsonii, Pseudomonas syringae, Enterobacter cloacae, and Lactococcus garvieae were the dominant species in the five samples. In addition to these bacterial species, we also detected some eukaryotes, such as Rhizophagus irregularis, Enterospora canceri, Smittium culicis, Zancudomyces culisetae, Trachipleistophora hominis, and viruses such as orf virus, human endogenous retrovirus type W, enzootic nasal tumor virus of goats, bovine retrovirus CH15, and galidia endogenous retrovirus in all of the samples at the species level. The results of the annotated KEGG pathway predictions for the gene functions of the midgut microflora of R. microplus indicated genes involved in lipid and amino acid metabolism, infectious diseases (e.g., Streptococcuspneumonia infection, human granulocytic anaplasmosis, Shigellasonnei infection, Salmonella enterica infection, and pathogenic Escherichia coli infection), and cancer.

Conclusions

Our study revealed that the midgut microbiome of R. microplus is not only composed of a large number of bacteria, but that a portion also comprises eukaryotes and viruses. The data presented here enhance our understanding of this tick’s midgut microbiome and provide fundamental information for the control of ticks and tick-borne diseases.

Graphical Abstract
The association between serum adropin and carotid atherosclerosis in patients with type 2 diabetes mellitus: a cross‑sectional study
Authors: Wei Wen , Liu Hui , Qiu Xiuping , Zhang Jushun , Huang Jianqing , Chen Hangju , Qiu Shuilin , Lin Ruiyu , Li Shihai , Tu Mei
Published: February 2022

Background

Adropin, a newly‑identified energy homeostasis protein, has been implicated in the maintenance of metabolic homeostasis and insulin sensitivity. This study attempts to measure the association between serum adropin and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).

Methods

This cross‑sectional study was performed in 503 hospitalized patients with T2DM.Serum adropin level was measured by a sandwich enzyme-linked immunosorbent assay. The carotid atherosclerosis was assessed by color Doppler sonography. The association between adropin and carotid atherosclerotic plaque was tested by logistic regression model. The effect of adropin on carotid intimal-medial thickness (CIMT) was estimated using linear regression model.

Results

Overall, 280 (55.7%) patients had carotid atherosclerotic plaque. The risk of carotid atherosclerotic plaque decreased with the increment of serum adropin level (adjusted odds ratio [aOR], 0.90; 95%CI: 0.81–0.99) in patients with T2DM. Serum adropin (Standardized β = − 0.006, p = 0.028) was also independently protective factor for CIMT in patients with T2DM.

Conclusion

In patients with T2DM, high serum adropin level was correlated with a decreased risk of carotid atherosclerosis in T2DM patients. Low circulating level of adropin may promote carotid atherosclerosis.
A protocol for prospective observational study to determine if non-anaemic iron deficiency worsens postoperative outcome in adult patients undergoing elective cardiac surgery: the IDOCS study
Authors: Miles Lachlan F. , Soo Vanessa Pac , Braat Sabine , Heritier Stephane , Burbury Kate L. , Story David A.
Published: February 2022

Background

Pre-operative anaemia has been associated independently with worse outcomes after cardiac surgery in adults and is often caused by absolute or functional iron deficiency. Iron deficiency is a continuum ending with anaemia, and therefore it is plausible that pre-operative early or ‘non-anaemic’ iron deficiency may also be associated with worse outcomes in patients undergoing cardiac surgery.

Methods

We have designed a prospective, observational study to determine if there is an association between non-anaemic iron deficiency and worse outcomes after cardiac surgery in adults. Patients without anaemia undergoing elective cardiac surgery will be allocated to an iron-deficient and an iron-replete group based on standard pre-operative blood tests (ferritin, transferrin saturation and C-reactive protein). The primary outcome is days alive and at home on postoperative day 30. The key secondary outcomes are days alive and at home on postoperative day 90 and readmission to acute care. Other secondary outcomes include health-related quality of life questionnaires, quality of postoperative recovery, postoperative complications, changes in haemoglobin concentration, and requirement for allogeneic blood products. The planned study sample size is 240 patients per group, which has 83% power to detect a median difference of 1.25 days in the primary outcome. The study commenced in March 2018, and recently completed recruitment, with data audit and cleaning ongoing.

Discussion

This study will be conducted using a rigorous, prospective observational design; it will provide peak bodies and clinicians with high-quality evidence concerning the associations between non-anaemic iron deficiency and patient-centred outcomes after elective cardiac surgery. Our primary and key secondary outcomes are known to have great importance to clinicians and patients alike and align with the recommendations of the StEP-COMPAC group for outcomes in prospective peri-operative research. The definition used for iron deficiency accounts for both absolute and functional iron deficiency and make use of standard pre-operative blood tests to make this determination, easing the transition of results into clinical practice. The study will be conducted in two relatively high-volume centres in a single high-income country. This limits the generalisability of study results to similar centres.

Trial registration

Australian and New Zealand Clinical Trials Registry (ACTRN12618000185268). Registered 5 February 2018.
French general practitioners’ and patients’ acceptability of a public commitment charter and patient information leaflets targeting unnecessary antibiotic use: a qualitative study
Authors: Essilini Anaïs , Le Dref Gaëlle , Bocquier Aurélie , Kivits Joëlle , Welter Adeline , Pulcini Céline , Thilly Nathalie ,   the AntibioCharte scientific committee
Published: February 2022

Background

The ‘AntibioCharte’ randomised controlled study aimed at assessing the impact of a multifaceted antibiotic stewardship intervention targeting French general practitioners with higher-than-average antibiotic use. The intervention included a public commitment charter signed by the general practitioner, a non-prescription pad, and a patient information leaflet.

Objectives

We conducted a qualitative study to evaluate general practitioners’ fidelity in the intervention and its acceptability by patients and general practitioners.

Methods

This investigation was performed in northeastern France from July 2019 to May 2020, among the AntibioCharte intervention group after a 1-year implementation period. General practitioners’ fidelity in the charter was assessed by direct observations; general practitioners’ fidelity in the other tools, and acceptability of both general practitioners and patients were assessed through semi-structured face-to-face individual interviews.

Results

Twenty-seven general practitioners and 14 patients participated. General practitioners’ fidelity varied according to the tool: the charter was clearly displayed in most waiting rooms; the non-prescription pad was used throughout the intervention period by most general practitioners while the leaflet was used by fewer general practitioners. Both general practitioners and patients found the charter’s content and form relevant, but few general practitioners felt themselves publicly engaged. The waiting room may not be appropriate to display the charter as some general practitioners forgot it and patients did not always read the displayed documents. General practitioners appreciated the pad and found that it could help them change their practices. It was perceived as a good tool to educate patients and manage their expectations for antibiotics. Patients appreciated the pad too, especially information on the infections’ symptoms and their duration. Still, some patients feared that it could encourage doctors not to prescribe antibiotics. Unlike general practitioners, who considered the leaflet redundant with the information given during the consultation, patients found it useful to raise awareness on antibiotics’ specificities and risks, and remind them of good practices.

Conclusions

The AntibioCharte intervention was overall well accepted by general practitioners and patients. The non-prescription pad was the best perceived tool.

Trial registration numberClinicalTrials.gov: NCT04562571.
Contributions of the microbiome to intestinal inflammation in a gut-on-a-chip
Authors: Jeon Min Seo , Choi Yoon Young , Mo Sung Jun , Ha Jang Ho , Lee Young Seo , Lee Hee Uk , Park Soo Dong , Shim Jae-Jung , Lee Jung-Lyoul , Chung Bong Geun
Published: February 2022

The intestinal microbiome affects a number of biological functions of the organism. Although the animal model is a powerful tool to study the relationship between the host and microbe, a physiologically relevant in vitro human intestinal system has still unmet needs. Thus, the establishment of an in vitro living cell-based system of the intestine that can mimic the mechanical, structural, absorptive, transport and pathophysiological properties of the human intestinal environment along with its commensal bacterial strains can promote pharmaceutical development and potentially replace animal testing. In this paper, we present a microfluidic-based gut model which allows co-culture of human and microbial cells to mimic the gastrointestinal structure. The gut microenvironment is recreated by flowing fluid at a low rate (21 μL/h) over the microchannels. Under these conditions, we demonstrated the capability of gut-on-a-chip to recapitulate in vivo relevance epithelial cell differentiation including highly polarized epithelium, mucus secretion, and tight membrane integrity. Additionally, we observed that the co-culture of damaged epithelial layer with the probiotics resulted in a substantial responded recovery of barrier function without bacterial overgrowth in a gut-on-a-chip. Therefore, this gut-on-a-chip could promote explorations interaction with host between microbe and provide the insights into questions of fundamental research linking the intestinal microbiome to human health and disease.
Effects of Hyperbaric Oxygen Therapy on Mitochondrial Respiration and Physical Performance in Middle-Aged Athletes: A Blinded, Randomized Controlled Trial
Authors: Hadanny Amir , Hachmo Yafit , Rozali Daniella , Catalogna Merav , Yaakobi Eldad , Sova Marina , Gattegno Hadar , Abu Hamed Ramzia , Lang Erez , Polak Nir , Friedman Mony , Finci Shachar , Zemel Yonatan , Bechor Yair , Gal Noga , Efrati Shai
Published: February 2022

Introduction

Hyperbaric oxygen therapy (HBOT) has been used to increase endurance performance but has yet to be evaluated in placebo-controlled clinical trials. The current study aimed to evaluate the effect of an intermittent HBOT protocol on maximal physical performance and mitochondrial function in middle-aged master athletes.

Methods

A double-blind, randomized, placebo-controlled study on 37 healthy middle-aged (40–50) master athletes was performed between 2018 and 2020. The subjects were exposed to 40 repeated sessions of either HBOT [two absolute atmospheres (ATA), breathing 100% oxygen for 1 h] or SHAM (1.02ATA, breathing air for 1 h).

Results

Out of 37 athletes, 16 HBOT and 15 SHAM allocated athletes were included in the final analysis. Following HBOT, there was a significant increase in the maximal oxygen consumption (VO2Max) (p = 0.010, effect size(es) = 0.989) and in the oxygen consumption measured at the anaerobic threshold (VO2AT)(es = 0.837) compared to the SHAM group. Following HBOT, there were significant increases in both maximal oxygen phosphorylation capacity (es = 1.085, p = 0.04), maximal uncoupled capacity (es = 0.956, p = 0.02) and mitochondrial mass marker MTG (p = 0.0002) compared to the SHAM sessions.

Conclusion

HBOT enhances physical performance in healthy middle-age master athletes, including VO2max, power and VO2AT. The mechanisms may be related to significant improvements in mitochondrial respiration and increased mitochondrial mass.

Trial Registration ClinicalTrials.gov Identifier: https://clinicaltrials.gov/ct2/show/NCT03524989 (May 15, 2018).
The feasibility, safety, and efficacy of upper limb garment-integrated blood flow restriction training in healthy adults
Authors: Dhokia Bhavit , Mabin Elspeth Olivia , Bradley Warren Jeremy , Neal Bradley Stephen
Published: February 2022

Background

Blood flow restriction training (BFR) has been demonstrated to increase muscle hypertrophy and strength, but has logistical and cost barriers. Garment-integrated BFR has the potential to reduce these barriers by lowering equipment demands and cost. The primary aim of the study was to explore the feasibility of garment-integrated BFR in the upper limb of healthy adults, with a secondary aim of exploring safety and efficacy.

Methods

Physically active and otherwise healthy participants with no previous experience with BFR were sought. Eligible participants completed a five-week garment-integrated BFR programme that involved completing two sessions per week. Feasibility was determined by a priori defined thresholds for recruitment, adherence to the garment-integrated BFR programme, and data collection. Safety was determined by recording adverse events and by monitoring for total arterial occlusion pressure using a fingertip pulse oximeter. Efficacy was determined by measuring push-ups to volitional failure, arm girth, and number of prescribed repetitions completed. Feasibility and safety outcomes were reported descriptively or as a proportion with associated 95% confidence intervals (95% CI). Mean change, 95% CIs, and associated effect sizes were calculated for efficacy outcomes.

Results

Twenty-eight participants were included (15 men, 13 women; mean age 31.6 years [±9.1]) and 27 successfully completed the study. Participants were successfully recruited within three months and 278/280 sessions were successfully completed (adherence=99.3%, 95% CI 97.4%, 99.9%). Minimal adverse events were reported; one incident of localised bruising (0.36%, 95% CI 0.06%, 2.0%) and three incidences of excessive pain during or post-exercise from two separate participants (1.07%, 95% CI 0.03%, 3.1%). 82/2240 pulse oximeter readings were not recorded (3.7%, 95% CI 2.9%, 4.5%). Mean push-ups to volitional failure increased by 40% (mean change=8.0, 95% CI 6, 10, d=1.40). Mean arm girth and number of prescribed repetitions completed were unchanged.

Conclusions

Garment-integrated BFR is feasible and has no signal of important harm in the upper limb of healthy adults, and could proceed to a future trial with stop/go criteria for randomisation. Further work is required to investigate the efficacy of garment-integrated BFR and determine its equivalence or superiority compared to existing BFR methods.
Age groups of De’ang people from a comparative perspective: a case study of De’ang people in Yunnan Province, China
Authors: Shu Yu
Published: February 2022

Based on comparison between age sets in Africa and the social age structure of the Dai people in China, this paper examines the forms, functions and evolution of the age groups of the De’ang people in Yunnan Province, China. The age groups of De’ang people are unique in that only two distinct age grades (the youth and the elderly) are organized, both of which have different social functions. This pattern provides an important reference for further discussion on the relationships between age sets and age grades, as well as forms and types of age-class systems.
Reconciling differences pertaining to the origin of SARS-CoV-2
Authors: Muhammad Yasin Ali
Published: February 2022

Background

At the time of this writing, SARS-CoV-2 has reportedly claimed the lives of millions of people worldwide. However, there is still disagreement concerning the origin of SARS-CoV-2, its true nature, and the extent of its pathogenicity. Thus, the purpose of this manuscript is to highlight and critically analyze these differences so that research efforts can be geared toward addressing these concerns.

Main Body

For this purpose, the author studied the perspectives of both conventional and non-conventional scientists, physicians, and researchers in an attempt to understand the points of contention and the reasons for the vast gulf in perspective.

Conclusion

After reviewing the varying but divergent perspective pertaining to the origin of SARS-CoV-2 and the premises used to justify them, it has become clear that if the scientific community is to put a halt to the spread of misinformation pertaining to the origin of SARS-CoV-2 and COVID-19, the predominant scientific community (particularly the microbiologist/immunologist) must carry out the requisite scientific procedures and encourage governmental/academic transparency.
Hand sanitizers as a preventive measure in COVID-19 pandemic, its characteristics, and harmful effects: a review
Authors: Prajapati Parixit , Desai Heli , Chandarana Chandni
Published: February 2022

Background

In the global health emergency caused by COVID-19, multiple experts have mandated the use of hand sanitizers as a safety measure from COVID-19. The sale of hand sanitizers has increased many folds. Therefore, when there is such large use of hand sanitizers, it becomes extremely important to study and understand hand sanitizers in a comprehensive manner.

Main body of the abstract

This article starts with the importance of sanitizers as a defence mechanism that is employed by the hand to fight against the coronavirus. This article provides information about history, types, composition, various dosage forms, and marketed formulations of hand sanitizers. The article sheds a detailed light on industrial production techniques for hand sanitizers and also outlines new innovative techniques that were employed by the industry to mass produce hand sanitizers in the wake of the pandemic. The article further dives into a comparison between hand sanitizers and soaps so as to give pros and cons of the use of soap against the use of hand sanitizers. One of the aims of the article is to study the side effects of sanitizers so as to develop a cautious approach while using hand sanitizers and therefore a comprehensive list of side effects of the use of hand sanitizers is given.

Conclusion

The review article finds that hand sanitizers are extremely efficient in fight the virus but along with it, it brings along arrange of risks which are outlined in the article.
COVID-19 and vaccination induced changes in hospital activity in Malta, Q1 2020 to Q1 2021: a population-based study
Authors: Cuschieri Sarah , Borg David , Agius Steve , Scherb Hagen , Grech Victor
Published: February 2022

Background

COVID-19 has severely impacted global healthcare services. Malta has only one acute state hospital, Mater Dei Hospital (MDH), and at the time of writing is the most vaccinated country in Europe. Malta thus provides an ideal setting to assess the impact of COVID-19 on healthcare services at population level, including the impact of vaccination on hospital admissions.

Methods

Hospital data was obtained as anonymised totals from MDH’s Clinical Performance Unit and the European Centre for Disease Prevention and Control. COVID-19-related data was obtained from the Ministry of Health dashboard. Comparative assessments were performed to explore associations between the COVID-19 situation, vaccination, and hospital activity. Poisson regression was used to model the counts of monthly accident and emergency (A&E), outpatient clinics attendances and hospital admissions.

Results

A&E, hospital admissions, and outpatient clinics attendances declined (31.88%; 23.89%; 29.57%; p < 0.01 respectively) with onset of COVID-19 till April 2021 when compared to pre-COVID years (2017–2019). Admissions due to COVID-19 initially increased in parallel to the population’s COVID positivity. Vaccination rollout led to a decline in COVID-19 admissions.

Conclusions

The drastic drop in admissions and outpatient attendees was expected but not for A&E attendees as acutely ill patients should still have attended. This is of public health concern since delayed or deferred medical management increases population morbidity, mortality and increases the eventual burden on the healthcare system. Mass vaccination saw the return to normality with an increase in A&E burden.
Accelerating CFD simulation with high order finite difference method on curvilinear coordinates for modern GPU clusters
Authors: Ye Chuang-Chao , Zhang Peng-Jun-Yi , Wan Zhen-Hua , Yan Rui , Sun De-Jun
Published: February 2022

A high fidelity flow simulation for complex geometries for high Reynolds number (Re) flow is still very challenging, requiring a more powerful HPC system. However, the development of HPC with traditional CPU architecture suffers bottlenecks due to its high power consumption and technical difficulties. Heterogeneous architecture computation is raised to be a promising solution to the challenges of HPC development. GPU accelerating technology has been utilized in low order scheme CFD solvers on the structured grid and high order scheme solvers on unstructured meshes. The high-order finite difference methods on structured grids possess many advantages, e.g., high efficiency, robustness, and low storage. However, the strong dependence among points for a high-order finite difference scheme still limits its application on the GPU platform. In the present work, we propose a set of hardware-aware technology to optimize data transfer efficiency between CPU and GPU, as well as communication efficiency among GPUs. An in-house multi-block structured CFD solver with high order finite difference methods on curvilinear coordinates is ported onto the GPU platform and obtains satisfying performance with a speedup maximum of around 2000x over a single CPU core. This work provides an efficient solution to apply GPU computing in CFD simulation with specific high order finite difference methods on current GPU heterogeneous computers. The test shows that significant accelerating effects can be achieved for different GPUs.
Varus stress MRI in diagnosis of medial meniscal posterior root tear
Authors: Qardash Ashgan Ali Abdo , Hassan Afaf A. , El kady Hesham A. , Mohammed Hosam El-Deen G. , Abdel-Tawab Mohamed , Mohammed Nisreen A. A.
Published: February 2022

Background

Early and accurate diagnosis of medial meniscal posterior root tear (MMPRT) via magnetic resonance imaging (MRI) is crucial to prevent the development of medial meniscus extrusion (MME) and subsequent osteoarthritic changes. The study aims to assess the role of MRI in diagnosing the medial meniscal posterior root tear (MMPRT) as well as to investigate the additive value of a new MRI technique (varus stress position technique) in measuring the accurate degree of a truly extruded meniscus, during normal daily activities like standing or walking. This prospective study included 70 patients who had an episode of posteromedial knee pain. All patients underwent conventional MRI, whereas only 35 of them underwent MRI with varus stress loading position.

Results

The study included 70 patients, of which 56 were female (80.0%), with a mean age of 49.1 ± 8.5 years. According to duration onset of MMPRT, 39 patients were in the chronic stage (4–12 months), 16 patients were in the acute stage (early < 1 month), and 15 patients were in the subacute stage (1–3 months). It was found that varus stress position could detect 100% of the patients (35/35) with positive medial meniscus extrusion (MME) (≥ 3 mm), whereas the MRI with the traditional position could detect only 62.9% of the cases (22/35) (P < 0.000). Regarding the chronicity of MMPRT, a significant increase was observed in the amount of MME in post-varus MRI compared with that in pre-varus MRI for each stage (acute, subacute, and chronic) (P < 0.000).

Conclusion

MRI is considered a superior imaging modality in diagnosing MMPRT through several characteristic MRI findings. The varus stress position showed a valuable role in assessing the presence and degree of severity of true extruded meniscus using positional varus stress load.
A self-guided and monitored digital problem-solving intervention for patients with symptoms of depression or anxiety on the waiting list for treatment in routine psychiatric care: feasibility study
Authors: Hentati Amira , Forsell Erik , Ljótsson Brjánn , Lindefors Nils , Kraepelien Martin
Published: February 2022

Background

There is often a waiting period for people who seek psychiatric treatment for depression or anxiety. As this delay risks worsening symptoms, an alternative could be to provide an intervention that requires minimal resources during the waiting period.

Aims

The aim was to investigate if a digital problem-solving intervention delivered in a self-guided format with automated features is feasible to provide for patients on the waiting list in routine psychiatric care.

Method

A total of 12 patients with symptoms of depression or anxiety on the waiting list for treatment in routine psychiatric care were given access to a self-guided and monitored digital problem-solving intervention over 4 weeks. Primary outcome measures were treatment credibility and usability. Secondary outcome measures were behavioural engagement, symptoms of depression and anxiety, and negative effects.

Results

A majority of participants rated the intervention as both credible and usable. The intervention was used at least once by nine out of 12 individuals, with an average of 11 logins. The participants did, on average, initiate 2.8 problem-solving attempts and 10.1 solutions. A few participants reached a clinically relevant symptom improvement of depression and anxiety. No serious negative effects were reported.

Conclusions

The credibility and usability of the intervention was perceived as good, and the behavioural engagement with the intervention was deemed sufficient compared with similar self-guided interventions. A self-guided and monitored digital problem-solving intervention may be a beneficial option for patients waiting for or receiving treatment in routine psychiatric care, and should be further evaluated.
Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F
Authors: Damodaran Senthil , Zhao Fengmin , Deming Dustin A. , Mitchell Edith P. , Wright John J. , Gray Robert J. , Wang Victoria , McShane Lisa M. , Rubinstein Larry V. , Patton David R. , Williams P. Mickey , Hamilton Stanley R. , Suga Jennifer M. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay N. , O'Dwyer Peter J. , Chen Alice P. , Flaherty Keith T.
Published: February 2022

PURPOSE

Activating mutations in PIK3CA are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform–specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations (with or without PTEN loss).

PATIENTS AND METHODS

Patients received copanlisib (60 mg intravenous) once weekly on days 1, 8, and 15 in 28-day cycles until progression or toxicity. Patients with KRAS mutations, human epidermal growth factor receptor 2–positive breast cancers, and lymphomas were excluded. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival, 6-month progression-free survival, and overall survival.

RESULTS

Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the Protocol. Multiple histologies were enrolled, with gynecologic (n = 6) and gastrointestinal (n = 6) being the most common. Sixty-eight percent of patients had ≥ 3 lines of prior therapy. The ORR was 16% (4 of 25, 90% CI, 6 to 33) with P = .0341 against a null rate of 5%. The most common reason for protocol discontinuation was disease progression (n = 17, 68%). Grade 3/4 toxicities observed were consistent with reported toxicities for PI3K pathway inhibition. Sixteen patients (53%) had grade 3 toxicities, and one patient (3%) had grade 4 toxicity (CTCAE v5.0). Most common toxicities include hyperglycemia (n = 19), fatigue (n = 12), diarrhea (n = 11), hypertension (n = 10), and nausea (n = 10).

CONCLUSION

The study met its primary end point with an ORR of 16% ( P = .0341) with copanlisib showing clinical activity in select tumors with PIK3CA mutation in the refractory setting.
Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes
Authors: van Ruiten Charlotte C , Veltman Dick J , Schrantee Anouk , van Bloemendaal Liselotte , Barkhof Frederik , Kramer Mark H H , Nieuwdorp Max , IJzerman Richard G
Published: February 2022

Context

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) cause less weight loss than expected based on urinary calorie excretion. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, leading to increased appetite and food intake. Glucagon-like peptide-1 receptor agonists are associated with reduced appetite and body weight, mediated by direct and indirect central nervous system (CNS) effects.

Objective

We investigated the separate and combined effects of dapagliflozin and exenatide on the CNS in participants with obesity and type 2 diabetes.

Methods

This was a 16-week, double-blind, randomized, placebo-controlled trial. Obese participants with type 2 diabetes (n = 64, age 63.5 ± 0.9 years, BMI 31.7 ± 0.6 kg/m2) were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide-matched placebo, exenatide twice daily 10 µg with dapagliflozin-matched placebo, dapagliflozin and exenatide, or double placebo. Using functional MRI, the effects of treatments on CNS responses to viewing food pictures were assessed after 10 days and 16 weeks of treatment.

Results

After 10 days, dapagliflozin increased, whereas exenatide decreased CNS activation in the left putamen. Combination therapy had no effect on responses to food pictures. After 16 weeks, no changes in CNS activation were observed with dapagliflozin, but CNS activation was reduced with dapagliflozin-exenatide in right amygdala.

Conclusion

The early increase in CNS activation with dapagliflozin may contribute to the discrepancy between observed and expected weight loss. In combination therapy, exenatide blunted the increased CNS activation observed with dapagliflozin. These findings provide further insights into the weight-lowering mechanisms of SGLT2i and GLP-1 receptor agonists.
Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study
Authors: Chen Delong , Zhang Yuxuan , Yidilisi Abuduwufuer , Xu Yi , Dong Qichao , Jiang Jun
Published: February 2022

Context

Observational studies have suggested associations between adipokines and cardiovascular disease (CVD), but the roles of certain adipokines remain controversial, and these associations have not yet been ascertained causally.

Objective

To investigate whether circulating adipokines causally affect the risk of CVD using 2-sample Mendelian randomization (MR).

Methods

Independent genetic variants strongly associated with adiponectin, resistin, chemerin, and retinol binding protein 4 (RBP4) were selected from public genome-wide association studies. Summary-level statistics for CVD, including coronary artery disease (CAD), myocardial infarction, atrial fibrillation (AF), heart failure (HF), and stroke and its subtypes were collected. The inverse-variance weighted and Wald ratio methods were used for the MR estimates. The MR pleiotropy residual sum and outlier, weighted median, MR-Egger, leave-one-out analysis, MR Steiger, and colocalization analyses were used in the sensitivity analysis.

Results

Genetically predicted resistin levels were positively associated with AF risk (odds ratio [OR] 1.09; 95% confidence interval [CI], 1.04-1.13; P = 4.1 × 10-5), which was attenuated to null after adjusting for blood pressure. We observed suggestive associations between higher genetically predicted chemerin levels and an increased risk of CAD (OR 1.27; 95% CI, 1.01-1.60; P = 0.040), higher genetically predicted RBP4 levels and an increased risk of HF (OR 1.14; 95% CI, 1.02-1.27; P = 0.024). There was no causal association between genetically predicted adiponectin levels and CVD risk.

Conclusions

Our findings reveal the causal association between resistin and AF, probably acting through blood pressure, and suggest potential causal associations between chemerin and CAD, RBP4, and HF.
Contribution of Clinical and Genetic Approaches for Diagnosing 209 Index Cases With 46,XY Differences of Sex Development
Authors: Gomes Nathalia Lisboa , Batista Rafael Loch , Nishi Mirian Y , Lerário Antônio Marcondes , Silva Thatiana E , de Moraes Narcizo Amanda , Benedetti Anna Flávia Figueredo , de Assis Funari Mariana Ferreira , Faria Junior José Antônio , Moraes Daniela Rodrigues , Quintão Lia Mesquita Lousada , Montenegro Luciana Ribeiro , Ferrari Maria Teresa Martins , Jorge Alexander A , Arnhold Ivo J P , Costa Elaine Maria Frade , Domenice Sorahia , Mendonca Berenice Bilharinho
Published: February 2022

Context

Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY differences of sex development (DSD).

Objective

To analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients.

Design/patients

209 nonsyndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into 3 subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS.

Results

Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except 1 case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively.

Conclusions

The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD.
Placental sFlt-1 Gene Delivery in Early Primate Pregnancy Suppresses Uterine Spiral Artery Remodeling
Authors: Aberdeen Graham W , Babischkin Jeffery S , Lindner Jonathan R , Pepe Gerald J , Albrecht Eugene D
Published: February 2022

Uterine spiral artery remodeling (SAR) is essential for promoting placental perfusion and fetal development. A defect in SAR results in placental ischemia and increase in placental expression and serum levels of the soluble fms-like tyrosine kinase-1 (sFlt-1) receptor that binds to and suppresses vascular endothelial growth factor (VEGF) bioavailability, thereby leading to maternal vascular dysfunction. We have established a nonhuman primate model of impaired SAR and maternal vascular dysfunction by prematurely elevating estradiol levels in early baboon pregnancy. However, it is unknown whether this primate model of defective SAR involves an increase in placental expression of sFlt-1, which may suppress VEGF bioavailability and thus SAR in the first trimester. Therefore, to establish the role of sFlt-1 in early pregnancy, SAR was quantified in baboons treated on days 25 through 59 of gestation (term = 184 days) with estradiol or with the sFlt-1 gene targeted selectively to the placental basal plate by ultrasound-mediated/microbubble-facilitated gene delivery technology. Placental basal plate sFlt-1 protein expression was 2-fold higher (P < 0.038) and the level of SAR for vessels > 25 µm in diameter was 72% and 63% lower (P < 0.01), respectively, in estradiol-treated and sFlt-1 gene-treated baboons than in untreated animals. In summary, prematurely elevating estradiol levels or sFlt-1 gene delivery increased placental basal plate sFlt-1 protein expression and suppressed SAR in early baboon pregnancy. This study makes the novel discovery that in elevated levels sFlt-1 has a role both in suppressing SAR in early primate pregnancy and maternal vascular endothelial function in late gestation.
Olig2 defines a subset of neural stem cells that produce specific olfactory bulb interneuron subtypes in the subventricular zone of adult mice
Authors: del Águila Ángela , Adam Mike , Ullom Kristy , Shaw Nicholas , Qin Shenyue , Ehrman Jacqueline , Nardini Diana , Salomone Joseph , Gebelein Brian , Lu Q. Richard , Potter Steven S. , Waclaw Ronald , Campbell Kenneth , Nakafuku Masato
Published: February 2022

Distinct neural stem cells (NSCs) reside in different regions of the subventricular zone (SVZ) and generate multiple olfactory bulb (OB) interneuron subtypes in the adult brain. However, the molecular mechanisms underlying such NSC heterogeneity remain largely unknown. Here, we show that the basic helix-loop-helix transcription factor Olig2 defines a subset of NSCs in the early postnatal and adult SVZ. Olig2-expressing NSCs exist broadly but are most enriched in the ventral SVZ along the dorsoventral axis complementary to dorsally enriched Gsx2-expressing NSCs. Comparisons of Olig2-expressing NSCs from early embryonic to adult stages using single cell transcriptomics reveal stepwise developmental changes in their cell cycle and metabolic properties. Genetic studies further show that cross-repression contributes to the mutually exclusive expression of Olig2 and Gsx2 in NSCs/progenitors during embryogenesis, but that their expression is regulated independently from each other in adult NSCs. Finally, lineage-tracing and conditional inactivation studies demonstrate that Olig2 plays an important role in the specification of OB interneuron subtypes. Altogether, our study demonstrates that Olig2 defines a unique subset of adult NSCs enriched in the ventral aspect of the adult SVZ.
Isaiah Andrews, 2021 John Bates Clark Medalist
Authors: Mikusheva Anna , Shapiro Jesse M.
Published: February 2022

Isaiah Andrews is an exceptionally warm and caring person, a remarkable teacher, a collaborator and mentor, an exemplary contributor to his department and profession, and a brilliant econometrician. In this article, we review Isaiah’s contributions to econometric theory in the context of Isaiah’s receipt of the 2021 John Bates Clark Medal.
Dental health status of community-dwelling adults aged 50 years and over in Ireland. A cross-sectional analysis of the Wave 3 TILDA cohort.
Authors: Naseer Amara , McLoughlin Jacinta , Donoghue Orna A. , Kenny Rose Anne , O'Connell Brian
Published: February 2022

Background: Little is known about the current oral health status of adults in Ireland. The aim of this study was to assess the dental health of community-dwelling adults aged 50 years and over in Ireland and to compare the current status to previous national surveys. 

Methods: The Irish Longitudinal Study on Ageing (TILDA) Wave 3 assessed the dental health of a subset of participants. Respondents attending for health assessments were offered a dental examination. The World Health Organization examination criteria were used.

Results:Of the 3111 people who were offered the dental assessment, 2525 were examined. Adults below 50 years of age and respondents whose dental health data were unavailable at the time of analysis were omitted, giving a final sample of 2504.  Among the dental assessment sample, 9.9% (249) were edentate. Of those aged 65 years and older, 15.6% were edentate while for the same age group 40.9% were edentate in the 2000-02 national survey. The mean number of teeth present in those aged 65 years or older was 14.9 for males and 14.2 for females, whereas in 2000-02 it was 9.9 and 7.4, respectively.  56.8% of the dentate sample had 10 or more tooth contacts. The mean DMFT of those aged 50 years or more was 18.5 and the Root Caries Index was 6.3. Between 2000-02 and 2014-5 (this study) in adults aged 65 years and over, the mean DMFT decreased from 25.9 to 20.1 and the Root Caries Index decreased from 11.6 to 9.1.

Conclusion: The results indicate the dental health of community-dwelling adults aged 50 years and over in Ireland improved since the previous survey of 2000-02. These improvements mean a change in the treatment needs of this age group and will require policy and service adjustments to meet these needs
Józef Półturzycki – niezwykła postać, wspaniały nauczyciel
Authors: Gromadzka Monika
Published: February 2022

Niniejszy artykuł jest krótkim opisem biografii naukowej jednego z najznakomitszych andragogów polskich, Prof. dra hab. Józefa Półturzyckiego. Okres jego życia zawodowego został podzielony na pięć etapów. Opis każdego z nich zawiera: przegląd podstawowych aktywności badawczych, ważne wydarzenia związane ze ścieżką zawodową, główne tematy podejmowane w publikacjach oraz działalność organizacyjną.
Edukacja (dorosłych) w dziedzinie bezpieczeństwa
Authors: Klimek Krzysztof
Published: February 2022

Bezpieczeństwo we współczesnym świecie stało się wartością bez- cenną, którą żywo zainteresowany jest niemal każdy, a pragnienie bezpiecznego życia zawsze było jedną z najważniejszych potrzeb ludzi. Niezwykle ważną rolę w kształtowaniu bezpieczeństwa odgrywa edukacja i dlatego zasadniczym jej celem w tym względzie jest przygotowanie człowieka do odpowiedniego działania w niebezpiecznych sytuacjach. Kształcenie dorosłych w zakresie edukacji dla bez- pieczeństwa wpisuje się zatem w idee edukacji ustawicznej, odnosząc się tym samym do odpowiedzialności (niemal obowiązku) każdego obywatela w zapewnieniu bezpieczeństwa samemu sobie i swoim bliskim. Stąd też podjęte rozważania w niniejszym artykule dotyczą właśnie problemów edukacji dorosłych w dziedzinie (na rzecz) bezpieczeństwa. Podstawę wyjściową zaś do ich wyjaśnienia stanowi wiedza o bezpieczeństwie i jego roli w życiu człowieka oraz o istocie prowadzonej edukacji dla bezpieczeństwa, rozpatrywanej w kontekście idei kształcenia całożyciowego.
Sprawozdanie z Międzynarodowej Konferencji pt. 100 lat uniwersytetów ludowych w wolnej Polsce (1921–2021), 4–5 października 2021 r., Mierzyn – Szczecin
Authors: Bzymek Agnieszka
Published: February 2022

W dniach 4–5 października 2021 r. miała miejsce Międzynarodowa Konferencja pt. 100 lat uniwersytetów ludowych w wolnej Polsce (1921–2021). Konferencja wyjątkowa. Wyjątkowość ta wyrażała się zarówno w doniosłości samego wydarzenia, jak i obecności wybitnych postaci, tematyce i treściach, niezwykłej atmosferze, jaka możliwa jest w obszarze spotkania badaczy oraz praktyków. Współorganizatorami konferencji byli: Zachodniopomorski Uniwersytet Ludowy w Mierzynie, Wydział Nauk Humanistycznych i Społecznych Akademii Marynarki Wojennej w Gdyni, Wydział Nauk Społecznych Uniwersytetu Szczecińskiego oraz Ogólnopolska Sieć Uniwersytetów Ludowych. Patronat Narodowy Prezydenta Rzeczypospolitej Polskiej Andrzeja Dudy w Stulecie Odzyskania Niepodległości wyraził się w odczytanym liście Prezydenta RP skierowanym do uczestników konferencji. Z kolei patronaty honorowe pełnili: Prof. dr hab. Piotr Gliński – Wiceprezes Rady Ministrów, Minister Kultury, Dziedzictwa Narodowego i Sportu, Wojciech Kaczmarczyk – Dyrektor Narodowego Instytutu Wolności. Patronat naukowy objęło Akademickie Towarzystwo Andragogiczne.
A family case report of Neurofibromatosis
Authors: Wolder Daniel , Swat Adrian
Published: February 2022

Neurofibromatosis is a genetic disease inherited in an autosomal, dominant manner. The course of von Recklinghausen’s disease varies from patient to patient. Most cases are mild and uncomplicated. The diagnosis of NF1 is based on the criteria of the National Institutes of Health (NIH). Type 2 neurofibromatosis is inherited, in most cases autosomal dominantly. The abnormal allele can be inherited from either parent, with the risk of passing the gene on to the offspring from the parent, being 50%. This article describes the familial form of neurofibromatosis. In the case in question, all three sisters were found to be mutated in the NF1 gene by genetic testing. In the same family, the clinical manifestation of the disease may be different for sisters and children. Due to compliance with medical recommendations, the disease does not significantly affect the quality of life of the families affected.
Logical Pluralism and Interpretations of Logical Systems
Authors: Tajer Diego , Fiore Camillo
Published: February 2022

Logical pluralism is a general idea that there is more than one correct logic. Carnielli and Rodrigues [2019a] defend an epistemic interpretation of the paraconsistent logic N4, according to which an argument is valid in this logic just in case it necessarily preserves evidence. The authors appeal to this epistemic interpretation to briefly motivate a kind of logical pluralism: “different accounts of logical consequence may preserve different properties of propositions”. The aim of this paper is to study the prospect of a logical pluralism based on different interpretations of logical systems. First, we give our analysis of what it means to interpret a logic – and make some hopefully useful distinctions along the way. Second, we present what we call an interpretational logical pluralism: there is more than one correct logic and a logic is correct only if it has some adequate interpretation. We consider four variants of this idea, bring up some possible objections, and try to find plausible solutions on behalf of the pluralist. We will argue that interpretations of logical systems provide a promising – albeit not unproblematic – route to logical pluralism.