bluuebunny/crossref_metadata_2025 huggingface dataset:
Palatability profile in spontaneously hypertensive rats
Authors: Pereira Emilson Donizete , De Luca Laurival A , Menani José Vanderlei , Andrade Carina Aparecida Fabrício
Published: April 2023

The spontaneously hypertensive rats (SHRs) have enhanced palatability for NaCl taste as measured by the increased number of hedonic versus aversive responses to intraoral infusion (1 mL/1 min) of 0.3 M NaCl, in a taste reactivity test in euhydrated condition or after 24 h of water deprivation + 2 h of partial rehydration (WD-PR). SHRs also ingested more sucrose than normotensive rats, without differences in quinine hydrochloride intake. Here, we investigated the palatability of SHRs (n = 8–10) and normotensive Holtzman rats (n = 8–10) to sucrose and quinine sulphate infused intraorally in the same conditions that NaCl palatability was increased in SHRs. SHRs had similar number of hedonic responses to 2% sucrose in euhydrated condition (95 ± 19) or after WD-PR (142 ± 25), responses increased when compared with normotensive rats in euhydrated condition (13 ± 3) or after WD-PR (21 ± 6). SHRs also showed increased number of aversive responses to 1.4 mM quinine sulphate compared with normotensive rats, whether in euhydrated condition (86 ± 6, vs. normotensive: 54 ± 7) or after WD-PR (89 ± 9, vs. normotensive: 40 ± 9). The results suggest that similar to NaCl taste, sweet taste responses are increased in SHRs and resistant to challenges in bodily fluid balance. They also showed a more intense aversive response in SHRs to bitter taste compared with normotensives. This suggests that the enhanced response of SHRs to taste rewards does not correspond to a decreased response to a typical aversive taste.
The ERA Registry Annual Report 2020: a summary
Authors: Astley Megan E , Boenink Rianne , Abd ElHafeez Samar , Trujillo-Alemán Sara , Arribas Federico , Åsberg Anders , Beckerman Pazit , Bell Samira , Bouzas-Caamaño María Encarnación , Farnés Jordi Comas , Galvão Ana Amélia , Gjorgjievski Nikola , Kelmendi Vjollca Godanci , Guidotti Rebecca , Helve Jaakko , Idrizi Alma , Indriðason Ólafur S , Ioannou Kyriakos , Kerschbaum Julia , Komissarov Kirill , Castro de la Nuez Pablo , Lassalle Mathilde , Nordio Maurizio , Arévalo Olga Lucía Rodríguez , Santiuste Carmen , Seyahi Nurhan , Roblero María Fernanda Slon , Steenkamp Retha , ten Dam Marc A G J , Zakharova Elena V , Ziginskiene Edita , Bonthuis Marjolein , Stel Vianda S , Ortiz Alberto , Jager Kitty J , Kramer Anneke
Published: April 2023

Background

The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with ESKD. This paper is a summary of the ERA Registry Annual Report 2020, also including comparisons among primary renal disease (PRD) groups.

Methods

Data were collected from 52 national and regional registries from 34 European countries and countries bordering the Mediterranean Sea: 35 registries from 18 countries providing individual level data and 17 registries from 17 countries providing aggregated data. Using this data, KRT incidence and prevalence, kidney transplantation rates, expected remaining lifetimes and survival probabilities were calculated.

Results

A general population of 654.9 million people was covered by the ERA Registry in 2020. The overall incidence of KRT was 128 per million population (p.m.p.). In incident KRT patients, 54% were older than 65 years, 63% were men and the most common PRD was diabetes mellitus (21%). Regarding initial treatment modality in incident patients, 85% received haemodialysis (HD), 11% received peritoneal dialysis (PD) and 4% received a pre-emptive kidney transplant. On 31 December 2020, the prevalence of KRT was 931 p.m.p. In prevalent patients, 45% were older than 65 years, 60% were men and glomerulonephritis was the most common PRD (18%). Of these patients, 58% were on HD, 5% on PD and 37% were living with a kidney transplant. The overall kidney transplantation rate in 2020 was 28 p.m.p., with a majority of kidney grafts from deceased donors (71%). The unadjusted 5-year survival, based on incident dialysis patient from 2011–15, was 41.8%. For patients having received a deceased donor transplant, the unadjusted 5-year survival probability was 86.2% and for patients having received a living donor transplant it was 94.4%. When comparing data by PRD group, differences were found regarding the distribution of age groups, sex and treatment modality received.
Pharmacological strategies to manage hyperkalaemia: out with the old, in with the new? Not so fast…
Authors: Carrero Juan Jesus , Sood Manish M , Gonzalez-Ortiz Ailema , Clase Catherine M
Published: April 2023

Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events.
The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison
Authors: Evans Marie , Dai Lu , Avesani Carla Maria , Kublickiene Karolina , Stenvinkel Peter
Published: April 2023

The profile of gut microbiota can vary according to host genetic and dietary characteristics, and be influenced by disease state and environmental stressors. The uremic dysbiosis results in a loss of biodiversity and overgrowth of microorganisms that may cause elevation of metabolic solutes such as trimethylamine N-oxide (TMAO), inducing pathogenic effects on its host. In patients with chronic kidney disease (CKD), TMAO levels are elevated because of a decreased clearance and an increased production from the uremic gut dysbiosis with a disrupted intestinal barrier and elevated enzymatic hepatic activity. Dietary precursors of TMAO are abundant in animal-derived foods such as red meat, egg yolk and other full-fat dietary products. TMAO is also found naturally in fish and certain types of seafood, with the TMAO content highly variable according to the depth of the sea where the fish is caught, as well as processing and storage. Although evidence points towards TMAO as being an important link to vascular damage and adverse cardiovascular outcomes, the evidence in CKD patients has not been consistent. In this review we discuss the potential dietary sources of TMAO and its actions on the intestinal microbiome as an explanation for the divergent results. We further highlight the potential of a healthy diet as one feasible therapeutic opportunity to prevent gut dysbiosis and reduce uremic toxin levels in patients with CKD.
εγ-Thalassemia, a New Hemoglobinopathy Category
Authors: Oliveira Jennifer L , Thompson Christineil H , Saravanaperumal Siva Arumugam , Koganti Tejaswi , Jenkinson Garrett , Hein Molly S , Kohorst Mira A , Hasadsri Linda , Nguyen Phuong L , Matern Dietrich , Kipp Benjamin R , Klee Eric W , Wieben Eric D , Hoyer James D , Rangan Aruna
Published: April 2023

Background

Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely disparate phenotypes, including variable degrees of microcytic anemia and Hb F levels. When present, increased Hb A2 is used as a surrogate marker for β-thalassemia. Notably, ϵγδβ-thalassemias lack the essential regulatory locus control region (LCR) and cause severe transient perinatal anemia but normal newborn screen (NBS) results and Hb A2 levels. Herein, we report a novel deletion of the ϵ, Aγ, Gγ, and ψβ loci with intact LCR, δ-, and β-regions in 2 women and newborn twins.

Methods

Capillary electrophoresis (CE), high-performance liquid chromatography (HPLC), DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), gap-polymerase chain reaction (gap-PCR), and long-read sequencing (LRS) were performed.

Results

NBS showed an Hb A > Hb F pattern for both twins. At 20 months, Hb A2 was increased similarly to that in the mother and an unrelated woman. Unexplained microcytosis was absent and the twins lacked severe neonatal anemia. MLPA, LRS, and gap-PCR confirmed a 32 599 base pair deletion of ϵ (HBE1) through ψβ (HBBP1) loci.

Conclusions

This deletion represents a hemoglobinopathy category with a distinct phenotype that has not been previously described, an ϵγ-thalassemia. Both the NBS Hb A > F pattern and the subsequent increased Hb A2 without microcytosis are unusual. A similar deletion should be considered when this pattern is encountered and appropriate test methods selected for detection. Knowledge of the clinical impact of this new category will improve genetic counselling, with distinction from the severe transient anemia associated with ϵγδβ-thalassemia.
How To Bind A TPM’s Attestation Keys With Its Endorsement Key
Authors: Chen Liqun , El Kassem Nada , Newton Christopher J P
Published: April 2023

A trusted platform module is identified by its endorsement key, while it uses an attestation key to provide attestation services, for example, signing a set of platform configuration registers, providing a timestamp or certifying another of its keys. This paper addresses the problem of how a certificate authority binds the endorsement and attestation keys together. This is necessary for the authority to be able to reliably certify the attestation key. This key binding also enables the authority to revoke the attestation key should the endorsement key be compromised. We study all of the existing solutions and show that they either do not solve the problem or cannot be implemented with a real trusted platform module (or both). We propose a new solution which addresses this problem. We develop a security model for our solution and provide a rigorous security proof under this model. We have also implemented the solution using a real trusted platform module, and our implementation results show that this solution is feasible and efficient.
Decreasing Proof Size of BLS Scheme
Authors: Fang Dong , Huang Guifang , Wang Mengfan , Hu Lei
Published: April 2023

Bootle et al. in CRYPTO 2019 proposed a zero knowledge proof for an $\mathrm{ISIS}_{m,n,q,\beta }$ instance $A\vec{s} = \vec{u} \bmod q$ with $\|\vec{s}\|_{\infty }\leq \beta $ (BLS scheme). It was implemented by transforming the instance into the form $A^{\prime }\vec{s}^{\prime } =\vec{u}\bmod q$, where the coefficients of $\vec{s}^{\prime}$ are in $\{0,1,2\}$, and proved the latter in an exact way. With the concrete parameters $m=1024,n=2048,\beta =1,q\approx 2^{32}$, their proof is of length 384.03KB. In this paper, we decrease the proof size of BLS scheme by two techniques. The first one takes effect on some special parameters. For these parameters, using the binary basic set instead of the ternary one results in a shorter proof. The second one deals with the repetition of the lower half in BLS scheme. Observing that what the lower half proves is of form $\mathbf{B}\vec{\mathbf{r}}=\vec{\mathbf{t}}$ with a short vector $\vec{\mathbf{r}}$ of polynomials, a variant of parallel repetition can be used to shorten the proof size. Combining these two techniques together, the proof size of the above-mentioned instance can be reduced to 220.01KB, only 57.3$\%$ of BLS scheme.
Graph model selection by edge probability prequential inference
Authors: Duvivier Louis , Cazabet Rémy , Robardet Céline
Published: April 2023

Graphs are widely used for describing systems made of many interacting components and for understanding the structure of their interactions. Various statistical models exist, which describe this structure as the result of a combination of constraints and randomness. In this article, we introduce edge probability prequential inference, a new approach to perform model selection, which relies on probability distributions on edge ensembles. From a theoretical point of view, we show that this methodology provides a more consistent ground for statistical inference with respect to existing techniques, due to the fact that it relies on multiple realizations of the random variable. It also provides better guarantees against overfitting, by making it possible to lower the number of parameters of the model below the number of observations. Experimentally, we illustrate the benefits of this methodology in two situations: to infer the partition of a stochastic blockmodel and to identify the most relevant model for a given graph between the stochastic blockmodel and the configuration model.
Integrated approach using insecticides in combination with reflective plastic mulch for the management of pepper weevil, Anthonomus eugenii (Coleoptera: Curculionidae)
Authors: Adeleye Victoria O , Seal Dakshina R , Liburd Oscar O E , Martini Xavier , Meru Geoffrey
Published: April 2023

Pepper weevil, Anthonomus eugenii Cano, is a serious pest of peppers (Capsicum annuum) in the United States and worldwide. This study evaluated the combined effect of insecticides (thiamethoxam and oxamyl) and reflective mulches (reflective silver on white and reflective silver on black) on pepper weevil suppression and yield increase. This study was conducted under field conditions in Homestead, FL, during the fall 2020, spring 2021, and 2022 growing seasons. The study consists of 2 mulch treatments as the main plots (reflective “silver on white,” “white on black”) and a bare ground with “no mulch” treatment in fall 2020 and spring 2021, and in spring 2022 with an additional treatment of reflective “silver on black” mulch. We hypothesized that jalapeño pepper grown on either reflective “silver on black” or “silver on white” plastic mulches would have fewer pepper weevil adults, fewer pepper weevil infested fruits, and higher yield than those grown on “white on black” plastic mulch or bare soil. Overall, the number of pepper weevil adults on plants and infested fruits was lower in the fall season compared to the spring season. In the fall 2020 season, the number of adults was not significantly different regardless of insecticide treatment and mulch type. However, infested fruits were higher on the untreated control plots than the treated plots in Fall 2020. Marketable yield was not significantly different among insecticide treatment on the “white on black” and reflective “silver on white” mulches. However, thiamethoxam treated plots had significantly higher yield than on the rest of the treatment on the bare soil with “no mulch.” The number of adults was higher in the untreated control plot than the treated plots in spring 2021. The number of infested fallen fruits was not significantly different. However, marketable yield was significantly different among treatments on the “white on black” and reflective “silver on white” mulches in 2021. The treated plots on the reflective “silver on white” mulch produced significantly higher yield than the untreated control plots in 2022. The result of this study suggests that growing jalapeño peppers on reflective plastic mulch (“silver on white”) in integration with thiamethoxam or oxamyl has the potential in reducing pepper weevil adult population and increasing yield of jalapeño pepper.
Biotic and abiotic factors that affect parasitism in Trichogramma pintoi (Hymenoptera: Trichogrammatidae) as a biocontrol agent against Heortia vitessoides (Lepidoptera: Pyralidae)
Authors: Yan Zhen , Yue Jian-Jun , Zhang Yong-Yu
Published: April 2023

The parasitoid wasp, Trichogramma pintoi, is a promising candidate for inundative release against Heortia vitessoides. Parasitoid females can regulate the sex of their offspring in response to environmental and biological factors. In pest control programs utilizing these parasitoids, male overproduction is not conducive to success. To optimize the production of T. pintoi as an egg parasitoid of H. vitessoides, factors affecting the rates of parasitism and eclosion and the percentage of females among T. pintoi offspring, such as temperature, photoperiod, host age, host density, maternal age, maternal density, and food, were investigated. The proportion of T. pintoi female offspring was significantly affected by temperature, photoperiod, host density, maternal age, and maternal density. The female offspring percentage decreased in response to host density (160 eggs), maternal age (≥ 4 days old), maternal density (≥ 4 females), photoperiods (24:0 and 18:6 L:D), and extremely low temperature (15 °C). However, host age and female diet did not affect the proportion of female offspring. According to the present work, female parasitoid production can be maximized under laboratory conditions of 25 °C, 75% relative humidity, and a photoperiod of 0:24 h (L:D) via exposure of forty 1-day-old H. vitessoides eggs for 24 h or eighty 1-day-old H. vitessoides eggs to a newly emerged, mated female fed a 10% sucrose solution until the female dies. These findings will guide mass production efforts for this parasitoid.
Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men
Authors: Kujala Iida , Nammas Wail , Maaniitty Teemu , Stenström Iida , Klén Riku , Bax Jeroen J , Knuuti Juhani , Saraste Antti
Published: April 2023

Aims

Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischaemia. We evaluated sex differences in disease profile and outcomes after combined computed tomography angiography (CTA) and positron emission tomography (PET) perfusion imaging in patients with suspected obstructive CAD.

Methods and results

We retrospectively evaluated 1948 patients (59% women) referred for coronary CTA due to suspected CAD during the years 2008–2016. Patients with a suspected obstructive lesion on coronary CTA (n = 657) underwent 15O-water PET to assess stress myocardial blood flow (MBF). During a mean follow-up of 6.8 years, 182 adverse events (all-cause death, myocardial infarction, or unstable angina) occurred. Women had more often normal coronary arteries (42% vs. 22%, P < 0.001) and less often abnormal stress MBF (9% vs. 28%, P < 0.001) than men. The annual adverse event rate was lower in women vs. men (1.2% vs. 1.7%, P = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0- and 5.6-fold adverse event rates in women and men, respectively. There was no interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse events.

Conclusion

Among patients evaluated for chronic chest pain, women have a lower prevalence of ischaemic CAD and a lower rate of adverse events. Combined coronary CTA and PET myocardial perfusion imaging predict outcomes equally in women and men.
Case Report: tacrolimus toxicity in the setting of concurrent Paxlovid use in a heart-transplant recipient
Authors: Modi Sujal , Kahwash Rami , Kissling Kevin
Published: April 2023

Background

Tacrolimus toxicity in patient’s status post-orthotropic heart transplantation is not commonly reported. Given its narrow therapeutic window and drug–drug interactions, it must be closely monitored by providers who are experienced in transplant management. There are no case series of patients with tacrolimus toxicity in the setting of treatment for Sars-2-CoV-19 (COVID 19) for heart-transplant recipients. We present a case of tacrolimus toxicity in the setting of concurrent ritonavir–nirmatrelvir (Paxlovid) use.

Case summary

The patient was a 74-year-old male with a prior significant history of heart transplantation and on maintenance immunosuppression with tacrolimus. He contracted COVID-19 and was prescribed antiviral therapy with Paxlovid by an outside provider prior to admission. The patient complained of severe headaches, dehydration, and tremors. After eliminating acute intracranial processes with imaging, laboratory investigation revealed a severely elevated tacrolimus level with acute renal injury. The patient was taken off tacrolimus and treated conservatively with intravenous hydration. The symptoms improved, particularly the headaches. He was discharged with instructions to resume his home dosing of tacrolimus and return to clinic in 1 week with a repeat trough level. The subsequent trough level was no longer supra-therapeutic.

Discussion

Tacrolimus has a potent drug-drug interaction with Paxlovid (ritonavir-nirmatrelvir) and can be supra-therapeutic. Toxicity is associated with multiple adverse effects, including but not limited to, acute renal injury, neurotoxicity, and infections due to over-immunosuppression. As Paxlovid is effective in treating Sars-2-CoV-19 in heart-transplant recipients, knowledge and understanding of drug-drug interactions is crucial in preventing and mitigating toxicity.
Impact of the extent of recurrent laryngeal nerve lymphadenectomy on thoracic esophageal squamous cell carcinoma: a real-world multicentre study
Authors: Xu Sukai , Chen Donglai , Liu Zhichao , Song Peidong , Zheng Yujia , Xue Xiang , Sang Yonghua , Li Zhigang , Chen Yongbing
Published: April 2023

OBJECTIVES

To determine the impact of recurrent laryngeal nerve (RLN) lymph node (LN) dissection on survival and postoperative complications in patients with oesophageal squamous cell carcinoma (ESCC).

METHODS

Patients with cT1-4N0-3M0 thoracic ESCC who underwent oesophagectomy and two-field lymphadenectomy from three institutions were included. The entire cohort was divided into three groups that underwent the total two-field lymphadenectomy (T-2FL), standard two-field lymphadenectomy (S-2FL) or unilateral RLN-LN dissection plus S-2FL (U-2FL) based on the extent of RLN-LN dissection. Subgroup analyses were also performed and were stratified by treatment modality.

RESULTS

Both the U-2FL and T-2FL groups had significantly superior outcomes compared with the S-2FL group (overall survival: U-2FL versus S-2FL: P = 0.002; T-2FL versus S-2FL: P < 0.001; recurrence-free survival: U-2FL versus S-2FL: P = 0.01; T-2FL versus S-2FL: P < 0.001). Moreover, no significant differences were observed between U-2FL and T-2FL regarding overall survival (P > 0.05) and recurrence-free survival (P > 0.05), irrespective of administration of neoadjuvant therapy plus oesophagectomy or upfront oesophagectomy. Additionally, the extent of RLN-LN dissection was not an independent predictor of stage migration (P = 0.14) but was for postoperative nodal upstaging (P = 0.02). Notably, S-2FL brought significantly lowered risk in postoperative complications, especially for RLN palsy, when compared with T-2FL (P = 0.002) but not U-2FL (P = 0.72).

CONCLUSIONS

Adequacy of RLN-LN dissection is an important prognosticator for improved overall survival and recurrence-free survival in patients with thoracic ESCC. U-2FL may serve as an alternative to T-2FL in selected populations.
Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium–glucose cotransporter 2 inhibitors
Authors: Packer Milton
Published: April 2023

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major heart failure events, an action that is statistically linked to enhanced erythropoiesis, suggesting that stimulation of erythropoietin and cardioprotection are related to a shared mechanism. Four hypotheses have been proposed to explain how these drugs increase erythropoietin production: (i) renal cortical reoxygenation with rejuvenation of erythropoietin-producing cells; (ii) counterregulatory distal sodium reabsorption leading to increased tubular workload and oxygen consumption, and thus, to localized hypoxia; (iii) increased iron mobilization as a stimulus of hypoxia-inducible factor-2α (HIF-2α)-mediated erythropoietin synthesis; and (iv) direct HIF-2α activation and enhanced erythropoietin gene transcription due to increased sirtuin-1 (SIRT1) signaling. The first two hypotheses assume that the source of increased erythropoietin is the interstitial fibroblast-like cells in the deep renal cortex. However, SGLT2 inhibitors do not alter regional tissue oxygen tension in the non-diabetic kidney, and renal erythropoietin synthesis is markedly impaired in patients with anemia due to chronic kidney disease, and yet, SGLT2 inhibitors produce an unattenuated erythrocytic response in these patients. This observation raises the possibility that the liver contributes to the production of erythropoietin during SGLT2 inhibition. Hypoxia-inducible factor-2α and erythropoietin are coexpressed not only in the kidney but also in hepatocytes; the liver is a major site of production when erythropoietin stimulation is maintained for prolonged periods. The ability of SGLT2 inhibitors to improve iron mobilization by derepressing hepcidin and ferritin would be expected to increase cytosolic ferrous iron, which might stimulate HIF-2α expression in both the kidney and liver through the action of iron regulatory protein 1. Alternatively, the established ability of SGLT2 inhibitors to enhance SIRT1 might be the mechanism of enhanced erythropoietin production with these drugs. In hepatic cell lines, SIRT1 can directly activate HIF-2α by deacetylation, and additionally, through an effect of SIRT in the liver, peroxisome proliferator-activated receptor-γ coactivator-1α binds to hepatic nuclear factor 4 to promote transcription of the erythropoietin gene and synthesis of erythropoietin. Since SIRT1 up-regulation exerts direct cytoprotective effects on the heart and stimulates erythropoietin, it is well-positioned to represent the shared mechanism that links erythropoiesis to cardioprotection during SGLT2 inhibition.
Using gamification to improve engagement and learning outcomes in medical microbiology: the case study of ‘BacteriaGame’
Authors: Pineros Nicolas , Tenaillon Katie , Marin Julie , Berry Vincent , Jaureguy Françoise , Ghelfenstein-Ferreira Théo , Carbonnelle Etienne , Lescat Mathilde
Published: April 2023

The fight against antibiotic resistance has become a true global public health challenge of gargantuan proportions. Amongst the myriad of approaches being explored to tackle this predicament, one strategy involves enhancing prescriber knowledge and in particular their basic knowledge of medical bacteriology. Yet, as we well know in medical microbiology teachings, traditional lectures can be arduous, attempting to cram in a vast array of information in a limited time. An alternative solution to improve student engagement and enhance learning outcomes is to utilize educational games in complementary approach. Such games are an effective means of inspiring students to learn, encouraging self-assessment, and injecting diversity into the teaching process. To this end, we have developed and evaluated an educational card game, the ‘BacteriaGame,’ aimed at our medical students in medical bacteriology. Designed for students at the basic level, it serves as activity at the end of their apprenticeship to their bacteriology education. Additionally, it can also be used as a review tool by more advanced students, with teachers able to impart additional knowledge as the game progresses. We also use it in continuous training of medical laboratory staff. In this study, we evaluated the game at various stages of medical education, collecting feedback and analysing its impact on knowledge acquisition, comparing it to traditional lectures. Feedback from the majority of students revealed that the rules were clear, the game was enjoyable, and neither too lengthy nor too challenging. The integration of ‘BacteriaGame’ into their future training piqued their interest. In terms of learning outcomes, we discovered a significant increase in knowledge acquisition among those who used the game (P < .05). ‘BacteriaGame’ is now published by the French Society of Microbiology (SFM) and distributed in all medical and pharmacy schools thanks to a funding of the French Health Ministry. An English edition of the game is also available for international use as a physical copy to be purchased from the SFM. This will allow a large-scale distribution to colleagues who would like to use this game in their teaching.
The Acinetobacter baumannii website (Ab-web): a multidisciplinary knowledge hub, communication platform, and workspace
Authors: Karah Nabil , Mateo-Estrada Valeria , Castillo-Ramírez Santiago , Higgins Paul G , Havenga Benjamin , Khan Wesaal , Domingues Sara , Da Silva Gabriela Jorge , Poirel Laurent , Nordmann Patrice , Ambrosi Cecilia , Ma Chaoying , McClean Siobhán , Quiroga María Paula , Alvarez Verónica E , Centron Daniela , Zarrilli Raffaele , Kenyon Johanna J , Russo Thomas A , Evans Benjamin A , Opazo-Capurro Andres , Rafei Rayane , Hamze Monzer , Daoud Ziad , Ahmad Irfan , Rather Philip N , Hall Ruth M , Wilharm Gottfried , Uhlin Bernt Eric
Published: April 2023

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Ab-web is a species-centric knowledge hub, initially with 10 articles organized into two main sections, ‘Overview’ and ‘Topics’, and three themes, ‘epidemiology’, ‘antibiotic resistance’, and ‘virulence’. The ‘workspace’ section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas.
Source estimation of the tsunami later phases associated with the 2022 Hunga Tonga volcanic eruption
Authors: Mizutani Ayumu , Yomogida Kiyoshi
Published: April 2023

On 15 January 2022, a large eruption of the Hunga Tonga-Hunga Ha’apai volcano in Tonga triggered globally observed tsunami waves. While the first arrival in the observed wave trains is now widely known to be related to the atmospheric Lamb wave generated by the eruption, large later phases, whose amplitudes were comparable to the first ones, were also recorded. In this study, we estimated the source of the later phases based on the Vespa analysis and proposed a new numerical scheme to reproduce them. The Vespa analysis estimates the arrival time and incident angle of each signal by a slant-stack process using its theoretical traveltime. The Vespa analysis revealed that small atmospheric waves excited the large later tsunamis. For the numerical experiments, we used two types of synthetic methods: finite difference method and normal mode theory. We found that both a good atmospheric wave model and bathymetric effect were important to generate the atmospheric-induced tsunamis corresponding to the later phases. A hybrid method calculating tsunamis by the finite difference method with the atmospheric waves by the normal mode theory as the input successfully reproduced the observed records, particularly in amplitude over the entire records.
Range contractions, fragmentation, species extirpations, and extinctions of commercially valuable molluscs in the Mediterranean Sea—a climate warming hotspot
Authors: Gallagher K M , Albano P G
Published: April 2023

The Mediterranean Sea is a global hotspot of climate warming and biodiversity loss where molluscs have provided valuable ecosystem services, such as provisioning and cultural value, since pre-historic times. A high rate of warming and range shift limitations due to the semi-enclosed nature of the basin raise concerns about molluscan population persistence in future climate scenarios. We modelled the future distribution of 13 Mediterranean species of molluscs subject to industrial fisheries exploitation on both the Mediterranean and Atlantic European coasts. We tested the hypothesis that range contractions, fragmentation, and species extirpations will become increasingly severe in the Mediterranean by modelling mid-century and end-century species distributions for four IPCC climate change scenarios. Already under mild emissions scenarios, substantial range contractions and fragmentation are projected in the Mediterranean, suggesting global extinctions by end-century for most endemic species. Colder deep waters do not act as refugia, contrary to expectations. Species also occurring along the Atlantic European coasts may benefit from warming through range expansions to higher latitudes or deeper waters. Most of the modeled species are already over-exploited, but their eradication from the Mediterranean will imply substantial financial losses and a profound cultural change in coastal communities.
Necessity of HuR/ELAVL1 for the activation-induced cytidine deaminase-dependent decrease in topoisomerase 1 in antibody diversification
Authors: Amin Wajid , Nishio Shoki , Honjo Tasuku , Kobayashi Maki
Published: April 2023

Activation-induced cytidine deaminase (AID)-dependent DNA cleavage is the initial event of antibody gene-diversification processes such as class switch recombination (CSR) and somatic hypermutation (SHM). We previously reported the requirement of an AID-dependent decrease of topoisomerase 1 (Top1) for efficient DNA cleavage, but the underlying molecular mechanism has remained elusive. This study focuses on HuR/ELAVL1, a protein that binds to AU-rich elements in RNA. HuR-knockout (KO) CH12 cells derived from murine B lymphoma cells were found to have lower CSR and hypermutation efficiencies due to decreased AID-dependent DNA cleavage levels. The HuR-KO CH12 cells do not show impairment in cell cycles and Myc expression, which have been reported in HuR-reduced spleen B cells. Furthermore, drugs that scavenge reactive oxygen species (ROS) do not rescue the lower CSR in HuR-KO CH12 cells, meaning that ROS or decreased c-Myc protein amount is not the reason for the deficiencies of CSR and hypermutation in HuR-KO CH12 cells. We show that HuR binds to Top1 mRNA and that complete deletion of HuR abolishes AID-dependent repression of Top1 protein synthesis in CH12 cells. Additionally, reduction of CSR to IgG3 in HuR-KO cells is rescued by knockdown of Top1, indicating that elimination of the AID-dependent Top1 decrease is the cause of the inefficiency of DNA cleavage, CSR and hypermutation in HuR-KO cells. These results show that HuR is required for initiation of antibody diversification and acquired immunity through the regulation of AID-dependent DNA cleavage by repressing Top1 protein synthesis.
Global Virtual Team Working during the Covid-19 Pandemic
Authors: Barry Phelim , Kane Bridget
Published: April 2023

Virtual work introduces distinct challenges when compared to face-to-face or on-site work. Communication and collaboration are key factors in team development and in team performance. When teamwork is of a global nature, imposed because of a pandemic, then additional variables are introduced into the equation. The challenges that global virtual teams (GVTs) encounter when communicating and developing in the context of the Covid-19 pandemic impacts how work is structured and teams develop. This qualitative study was conducted just over 1 year after the start of the Covid-19 pandemic when working from home became mandatory and particular challenges for GVTs became apparent. Data are gathered through an online anonymous survey and followed by semi-structured video-mediated interviews with staff in a large multinational software development company. Findings show that GVTs encounter a number of distinct challenges than face-to-face teams. However, individuals are actively adapting to the situation in which they find themselves and are learning to deal with the challenges by being proactive. Even though the tools used previously may not be entirely suitable for virtual work, GVTs learn to change how tools are used to be more productive and collaborative. Challenges continue to exist in areas, such as knowledge gathering and knowledge sharing. Communication failures can lead to delays and confusion. The findings also indicate that even though GVTs are not communicating as much informally or socially with their colleagues because of remote working in the pandemic, being remote is not having a negative effect on the ability to get work done. Some aspects of team development can be negatively affected when working in GVTs. Impacts are identified relating to trust and relationship building, as well as being able to identify and resolve conflict. These results prompt further research opportunities as organizations and individuals continue to adapt and embrace global virtual teamwork.
Real-life experience with remdesivir for treatment of COVID-19 among older adults: a multicentre retrospective study
Authors: Margalit Ili , Tiseo Giusy , Ripa Marco , Borghi Vanni , Green Hefziba , Prendki Virginie , Riccardi Niccolò , Perego Giovanni Battista , Grembiale Alessandro , Galli Laura , Tinelli Marco , Castagna Antonella , Mussini Cristina , Falcone Marco , Yahav Dafna
Published: April 2023

Introduction

The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data.

Methods

Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support.

Results

Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70–84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37–0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.

Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46–10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09–1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07–1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities.

Conclusions

Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.
Factors associated with the time and magnitude of the nadir body condition score in early lactation and its subsequent effects on fertility of Holstein cows
Authors: Hernandez-Gotelli Constanza , Manríquez Diego , Azocar Joaquin , De Vries Albert , Pinedo Pablo J
Published: April 2023

The objective of this study was to identify variables associated with the time and magnitude of nadir BCS (nBCS) during early lactation and to characterize the effects of these two measurements on the subsequent pregnancy at first artificial insemination (P/AI1) and pregnancy loss of Holstein cows. A retrospective observational study was completed using data collected from 12,042 lactations in 7,626 Holstein cows calving between April 2019 and January 2022 in a commercial dairy operation located in Colorado, USA. Scores generated by an automated BCS camera system at dry-off (BCSdry), calving (BCS1), nadir (nBCS; defined as the lowest daily BCS from calving to 100 DIM), and 21 d post nadir were selected for the analyses and subsequently categorized into quartiles (Q1 = lower nBCS). Changes in BCS were calculated from dry-off to calving (multiparous cows); from calving to nadir; and from nadir to 21 d post nadir and assigned into quartile categories considering Q1 as the 25% of cows with greater loss (pre nadir) or smaller gain (post nadir) of BCS. Data were examined using logistic regression, ANOVA, and time to event analyses. Initial univariable models were followed by multivariable models that considered parity category, calving season, BCS1, and average milk yield up to 30 DIM (M30) as covariables. Sick cows and high producing cows had increased DIM at nadir, while lower BCSdry, greater M30, and occurrence of disease were associated with lower nBCS. Cows that conceived at AI1 had their nBCS earlier (45.1 ± 0.32 d) than cows that remained open after first AI (46.4 ± 0.35 d). On the contrary, DIM at nBCS did not differ by pregnancy loss status. The logistic regression analyses reported smaller odds of P/AI1 in cows in the lower nBCS categories. Likewise, cows with larger loss in BCS between calving and nadir had smaller odds of P/AI1. Although cows that lost their pregnancy had lower nBCS, this association was not consistent across the analyses. The time to and magnitude of nBCS, together with the ∆BCS from calving to nadir could be useful measures to evaluate the transition and early lactation status of dairy cows.
Dietary supplementation of dimethyl itaconate protects against chronic heat stress-induced growth performance impairment and lipid metabolism disorder in broiler chickens
Authors: Li Longlong , Cui Ziyi , Wang Huihui , Huang Benzeng , Ma Haitian
Published: April 2023

This study aimed to investigate the protective effects of dietary supplementation of dimethyl itaconate (DI) on chronic heat stress (HS)-induced impairment of the growth performance and lipid metabolism in broiler chickens. 21 days old male Ross 308 broiler chickens (a total of 120, about 700 g body weight) were randomly divided into five treatment groups, including control group, HS group, HS + 50 mg/kg DI group, HS + 150 mg/kg DI group, and HS + 200 mg/kg DI group, and each group contains eight cages of twenty-four broilers. The broiler chickens in the control group were raised in the room (21 ± 1 °C) and fed with a finisher diet for 21 days. The broiler chickens of the HS group and the HS + DI groups were raised in the room (32 ± 1 °C for 8 h/day) and fed with a finisher diet containing DI at 0, 50, 150, and 200 mg/kg diet for 21 days. The results showed that HS-induced decreases in the final body weight (P < 0.01), average daily gain (P < 0.01), and average daily feed intake (P < 0.01) were alleviated by dietary supplementation of DI (P < 0.05). In addition, dietary supplementation of DI attenuated the increases in the liver index (P < 0.01) and abdominal fat rate (P < 0.01) caused by HS in broilers (P < 0.05). Treatment with DI ameliorated HS-induced lipid accumulation in the liver and serum of broiler chickens (P < 0.05). The upregulation of mRNA levels of fat synthesis factors (P < 0.01) and downregulation of mRNA levels of lipolysis-related factors (P < 0.01) caused by HS were markedly blunted after treatment with DI in the liver of broilers (P < 0.05). Broilers exposed to HS exhibited lower phosphorylated protein levels of AMP-activated protein kinase α and acetyl-CoA carboxylase α compared to the control group (P < 0.01), which were improved by treatment with DI (P < 0.01). Collectively, these results demonstrated that dietary supplementation of DI protects against chronic HS-induced growth performance impairment and lipid metabolism disorder in broiler chickens. These results not only provide a theoretical basis for DI to alleviate metabolic disorders but also provide a reference value for DI as a feed additive to improve heat stress in poultry caused by high temperature.
Fabrication, design, and optimization of hierarchical composite Kagome honeycomb sandwich structure under uniaxial compression
Authors: Song Shijun , Xiong Chao , Yin Junhui , Yang Zhaoshu , Wang Lu
Published: April 2023

In this study, a hierarchical composite Kagome honeycomb sandwich (HCKHS) structure was manufactured based on the interlocking method, and its uniaxial compression performance was explored. Through experiments, the compressive strength, stiffness, energy absorption, and failure process of HCKHS specimens of seven different sizes were determined and compared. Mechanical analytical models were established, and the variation trend in the specific strength was predicted and compared with those of other advanced sandwich structures. The size effect of the HCKHS specimens was analyzed. The influence of a single variable on the core modulus, failure strength, and failure modes was discussed, and failure mechanism maps were drawn. The structure was optimized based on the maximum specific strength and engineering application, and the optimal size design ratio was obtained. The results showed that the HCKHS specimens exhibited excellent compressive properties with a convenient manufacturing process, making them suitable for lightweight applications in engineering. The optimization ideas presented herein are also applicable to other two-dimensional hierarchical or normal composite honeycomb sandwich structures with diamond, triangular, and hexagonal shapes.
Fully mechanical motion-scaling instrument for microsurgery assistance: design improvement for enhancing the dynamic performance
Authors: Lee Tae-Hoon , Choi Dongeun , Kim Chunwoo
Published: April 2023

Robot assistance can improve the outcome of microsurgery by scaling down the surgeon’s hand motions. However, the high cost of surgical robots has prevented their use in small hospitals or medical facilities in several developing countries. As a novel alternative, a fully mechanical motion-scaling instrument, which can be operated without computers and motors, was proposed based on the pantograph mechanism. However, it had several problems owing to the cumbersome and heavy structures during the prototype test. This study aims solving the problems found in the first design and proving the advantages of the improvement, based on the design and performance criteria. The pantograph structure was simplified, and the gravity compensation method was modified to reduce inertia by using a constant force spring instead of a counter-mass. The improvement was computationally predicted using a mathematical model, and the results were verified through trajectory measurements in a micropositioning task. Finally, the evaluation of dynamic performance is quantitatively presented through iterative positioning tasks.
Getting Pragmatic about Human Rights Pragmatism
Authors: Goldston James A
Published: April 2023

This review essay considers Jack Snyder’s Human Rights for Pragmatists: Social Power in Modern Times and explores the book’s key implications for human rights practitioners and their organizations.