bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of monoclonal antibodies targeting the conserved fragment of hexon protein to detect different serotypes of human adenovirus
Authors: Wu Linfan , Lin Yuhao , Yin Juzhen , Yang Changbi , Jiang Yushan , Zhai Linlin , Wang Yuelin , Zhu Li , Wu Qinghua , Zhang Bao , Wan Chengsong , Zhao Wei , Yang Yang , Shen Chenguang , Xiao Weiwei
Published: February 2024

Human adenovirus (HAdV) infects the respiratory system, thus posing a threat to health. However, immunodiagnostic reagents for human adenovirus are limited. This study aimed to develop efficient diagnostic reagents based on monoclonal antibodies for diagnosing various human adenovirus infections. Evolutionary and homology analyses of various human adenoviral antigen genes revealed highly conserved antigenic fragments. The prokaryotic expression system was applied to recombinant penton, hexon, and IVa2 conserved fragments of adenovirus, which were injected into BALB/c mice to prepare human adenovirus-specific monoclonal antibodies. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Western blotting were used to determine the immune specificity of the monoclonal antibodies. Indirect ELISA showed that monoclonal antibodies 1F10, 8D3, 4A1, and 9B2 were specifically bound to HAdV-3 and HAdV-55 and revealed high sensitivity and low detection limits for various human adenoviruses. Western blotting showed that 1F10 and 8D3 specifically recognized various human adenovirus types, including HAdV-1, HAdV-2, HAdV-3, HAdV-4, HAdV-5, HAdV-7, HAdV-21, and HAdV-55, and 4A1 specifically recognized HAdV-1, HAdV-2, HAdV-3, HAdV-5, HAdV-7, HAdV-21, and HAdV-55. IFAs showed that 1F10, 8D3, and 4A1 exhibited highly selective localization to A549 cells infected with HAdV-3 and HAdV-55. Finally, two antibody pairs that could detect hexon antigens HAdV-3 and HAdV-55 at low concentrations were developed. The monoclonal antibodies developed in this study show potential for detecting human adenoviruses.

IMPORTANCE

In this study, we selected the three most conserved antigenic fragments of human adenovirus to prepare a murine monoclonal antibody for the first time, and human adenovirus antigenic fragments with heretofore unheard of degrees of conservatism were isolated. The three monoclonal antibodies with the ability to recognize human respiratory adenovirus over a broad spectrum were screened by hybridoma and monoclonal antibody preparation. Human adenovirus infections are serious; however, therapeutic drugs and diagnostic reagents are scarce. Thus, to reduce the serious consequences of human viral infections and adenovirus pneumonitis, early diagnosis of infection is required. The present study provides three monoclonal antibodies capable of recognizing a wide range of human adenoviruses, thereby offering guidance for subsequent research and development.
Analysis on the change of gut microbiota and metabolome in lung transplant patients
Authors: Hou Zhichao , Zhang Tangjuan , Ding Zheng , Qian Ting , Wang Peng , Wu Bo , Pan Xue , Li Xiangnan
Published: February 2024

Previous studies have shown that the gut microbiota and its metabolites are associated with the success of organ transplantation. However, the specific changes in the gut microbiota of lung transplant patients remain unclear. Hence, this study aimed to elucidate the interplay between the gut microbiota, metabolome, and lung transplantation outcomes. Using 16S metagenomics sequencing and untargeted metabolic profiling, we conducted a comprehensive analysis of gut microbial and metabolic alterations in lung transplant recipients relative to non-transplant group. Our findings revealed the predominance of
Enterococcus
and
Streptococcus
genera within the lung transplant cohort, accompanied by the significant reduction in
Bacteroides
,
Epulopiscium
,
Faecalibacterium
, and
Prevotella
abundance. In addition, a significant reduction in ATRA (all-trans retinoic acid) levels and suppression of IgA production were observed in lung transplant recipients, which were found to be closely associated with the
Enterococcus
genus. It was speculated that the association might have implications for the prognosis of lung transplant patients. Notably, the differences in gut microbial composition and metabolomic profiles between successful transplant recipients and those experiencing chronic rejection were not statistically significant. These novel insights shed light on the putative implications of the gut microbiota and metabolome in shaping lung transplantation outcomes, and provide a foundation for future investigations and targeted therapeutic interventions.

IMPORTANCE

This study has profound implications for lung transplantation as it uncovers the important role of gut microbiota and metabolome in shaping transplantation outcomes. The identification of dominant bacterial genera, such as
Enterococcus
and
Streptococcus
, within the lung transplant cohort, along with the significant decrease in
Bacteroides
,
Epulopiscium
,
Faecalibacterium
, and
Prevotella
abundance, reveals potential microbial imbalances associated with lung transplantation. In addition, a significant reduction in ATRA (all-trans retinoic acid) levels and suppression of IgA production were observed in lung transplant recipients, which were found to be closely associated with the
Enterococcus
genus. It was speculated that the association might have implications for the prognosis of lung transplant patients. These findings hold immense clinical significance as they lay the groundwork for future research and targeted therapeutic interventions. Understanding the impact of the gut microbiota and metabolome on lung transplantation outcomes offers promising avenues for improving transplantation patient prognosis.
Jura-Cretaceous synorogenic magmatism and relations to supercontinental rifting in the northwestern U.S. Cordillera
Authors: Gray Keith D. , Johnson K. , Foster David A. , Isakson V.
Published: February 2024

Changes in lithospheric composition and strength associated with rifting of the Rodinian supercontinent (ca. 780–485 Ma) served to localize Mesozoic tectonic activity in the McCall region of west-central Idaho, USA. Although discrimination diagrams support slab failure melting, ca. 150–121 Ma calcic magmatism in the Hazard Creek complex and chemically similar intrusive rocks of northeastern Oregon, USA (e.g., Cornucopia stock), is best explained by progressive loading of oceanic crust. Westward-directed thrusting across the Laurentian continental margin and adjacent island-arc terranes (Olds Ferry/Wallowa; Blue Mountains province) led to partial melting of metabasaltic source rocks at pressures and depths sufficient for garnet stability (>10 kbar, ~35 km). Early pluton emplacement during right-oblique arc–continent collision overlapped in time with subduction zone reorganization, which involved a change in dip direction (westward to eastward) under the accreting Blue Mountains block. Ensuing magmatic activity predated and was concurrent with ca. 116 Ma thrust reactivation of the Wallowa/Olds Ferry boundary, which temporally overlapped with contractional deformation along the terrane–continent accretionary boundary. Later synorogenic magmatism was focused along the accretionary boundary, where rising anatectic melts were caught between the eastward-impinging/northward-migrating (obliquely colliding) terrane block and continental margin backstop (Rodinian rift architecture). Middle Cretaceous dextral transpression viewed in this manner precludes the need for an outboard “hit-and-run” collider (Insular superterrane) and thus, a post-accretion shear zone in western Idaho.
A model-based approach to estimating the prevalence of disease combinations in South Africa
Authors: Johnson Leigh F , Kassanjee Reshma , Folb Naomi , Bennett Sarah , Boulle Andrew , Levitt Naomi S , Curran Robyn , Bobrow Kirsty , Roomaney Rifqah A , Bachmann Max O , Fairall Lara R
Published: February 2024

Background

The development of strategies to better detect and manage patients with multiple long-term conditions requires estimates of the most prevalent condition combinations. However, standard meta-analysis tools are not well suited to synthesising heterogeneous multimorbidity data.

Methods

We developed a statistical model to synthesise data on associations between diseases and nationally representative prevalence estimates and applied the model to South Africa. Published and unpublished data were reviewed, and meta-regression analysis was conducted to assess pairwise associations between 10 conditions: arthritis, asthma, chronic obstructive pulmonary disease (COPD), depression, diabetes, HIV, hypertension, ischaemic heart disease (IHD), stroke and tuberculosis. The national prevalence of each condition in individuals aged 15 and older was then independently estimated, and these estimates were integrated with the ORs from the meta-regressions in a statistical model, to estimate the national prevalence of each condition combination.

Results

The strongest disease associations in South Africa are between COPD and asthma (OR 14.6, 95% CI 10.3 to 19.9), COPD and IHD (OR 9.2, 95% CI 8.3 to 10.2) and IHD and stroke (OR 7.2, 95% CI 5.9 to 8.4). The most prevalent condition combinations in individuals aged 15+ are hypertension and arthritis (7.6%, 95% CI 5.8% to 9.5%), hypertension and diabetes (7.5%, 95% CI 6.4% to 8.6%) and hypertension and HIV (4.8%, 95% CI 3.3% to 6.6%). The average numbers of comorbidities are greatest in the case of COPD (2.3, 95% CI 2.1 to 2.6), stroke (2.1, 95% CI 1.8 to 2.4) and IHD (1.9, 95% CI 1.6 to 2.2).

Conclusion

South Africa has high levels of HIV, hypertension, diabetes and arthritis, by international standards, and these are reflected in the most prevalent condition combinations. However, less prevalent conditions such as COPD, stroke and IHD contribute disproportionately to the multimorbidity burden, with high rates of comorbidity. This modelling approach can be used in other settings to characterise the most important disease combinations and levels of comorbidity.
Health journal coverage of climate change and health: a bibliometric study
Authors: Muhia Joy , Rethlefsen Melissa L , Rossington Ben , Wedmore Florence , Pattnaik Anandita , Smith Richard , Schroter Sara
Published: February 2024

Objectives

To find what proportion of a broad set of health journals have published on climate change and health, how many articles they have published, and when they first published on the subject.

Design

Bibliometric study.

Setting and participants

We conducted electronic searches in Ovid MEDLINE ALL for articles about climate change and human health published from 1860 to 31 December 2022 in 330 health journals. There were no limits by language or publication type. Results were independently screened by two raters for article eligibility.

Results

After screening there were 2932 eligible articles published across 253 of the 330 journals between 1947 and 2022; most (2795/2932; 95%) were published in English. A few journals published articles in the early 90s, but there has been a rapid increase since about 2006. We were unable to categorise the types of publication but estimate that fewer than half are research papers. While articles were published in journals in 39 countries, two-thirds (1929/2932; 66%) were published in a journal published in the UK or the USA. Almost a quarter (77/330; 23%) of the journals published no eligible articles, and almost three-quarters (241/330; 73%) published five articles or fewer. The publication of joint editorials in over 200 journals in 2021 and 2022 boosted the number of journals publishing something on climate change and health. A third of the (112/330; 34%) journals in our sample published at least one of the joint editorials, and almost a third of those (32/112; 29%) were publishing on climate change and health for the first time.

Conclusions

Health journals are rapidly increasing the amount they publish on climate change and health, but despite climate change being the major threat to global health many journals had until recently published little or nothing. A joint editorial published in multiple journals increased coverage, and for many journals it was the first thing they published on climate change and health.
Effectiveness and cost effectiveness of pharmacological thromboprophylaxis for medical inpatients: decision analysis modelling study
Authors: Davis Sarah , Goodacre Steve , Horner Daniel , Pandor Abdullah , Holland Mark , de Wit Kerstin , Hunt Beverley J , Griffin Xavier Luke
Published: February 2024

Objective

To determine the balance of costs, risks, and benefits for different thromboprophylaxis strategies for medical patients during hospital admission.

Design

Decision analysis modelling study.

Setting

NHS hospitals in England.

Population

Eligible adult medical inpatients, excluding patients in critical care and pregnant women.

Interventions

Pharmacological thromboprophylaxis (low molecular weight heparin) for all medical inpatients, thromboprophylaxis for none, and thromboprophylaxis given to higher risk inpatients according to risk assessment models (Padua, Caprini, IMPROVE, Intermountain, Kucher, Geneva, and Rothberg) previously validated in medical cohorts.

Main outcome measures

Lifetime costs and quality adjusted life years (QALYs). Costs were assessed from the perspective of the NHS and Personal Social Services in England. Other outcomes assessed were incidence and treatment of venous thromboembolism, major bleeds including intracranial haemorrhage, chronic thromboembolic complications, and overall survival.

Results

Offering thromboprophylaxis to all medical inpatients had a high probability (>99%) of being the most cost effective strategy (at a threshold of £20 000 (€23 440; $25 270) per QALY) in the probabilistic sensitivity analysis, when applying performance data from the Padua risk assessment model, which was typical of that observed across several risk assessment models in a medical inpatient cohort. Thromboprophylaxis for all medical inpatients was estimated to result in 0.0552 additional QALYs (95% credible interval 0.0209 to 0.1111) while generating cost savings of £28.44 (−£47 to £105) compared with thromboprophylaxis for none. No other risk assessment model was more cost effective than thromboprophylaxis for all medical inpatients when assessed in deterministic analysis. Risk based thromboprophylaxis was found to have a high (76.6%) probability of being the most cost effective strategy only when assuming a risk assessment model with very high sensitivity is available (sensitivity 99.9% and specificity 23.7%vbase case sensitivity 49.3% and specificity 73.0%).

Conclusions

Offering pharmacological thromboprophylaxis to all eligible medical inpatients appears to be the most cost effective strategy. To be cost effective, any risk assessment model would need to have a very high sensitivity resulting in widespread thromboprophylaxis in all patients except those at the very lowest risk, who could potentially avoid prophylactic anticoagulation during their hospital stay.
Understanding effect size: an international online survey among psychiatrists, psychologists, physicians from other medical specialities, dentists and other health professionals
Authors: Heimke Ferdinand , Furukawa Yuki , Siafis Spyridon , Johnston Bradley C. , Engel Rolf R. , Furukawa Toshi A , Leucht Stefan
Published: February 2024

Background and objective

Various ways exist to display the effectiveness of medical treatment options. This study examined various psychiatric, medical and allied professionals’ understanding and perceived usefulness of eight effect size indices for presenting both dichotomous and continuous outcome data.

Methods

We surveyed 1316 participants from 13 countries using an online questionnaire. We presented hypothetical treatment effects of interventions versus placebo concerning chronic pain using eight different effect size measures. For each index, the participants had to judge the magnitude of the shown effect, to indicate how certain they felt about their own answer and how useful they found the given effect size index.

Findings

Overall, 762 (57.9%) participants fully completed the questionnaire. In terms of understanding, the best results emerged when both the control event rate (CER) and the experimental event rate (EER) were presented. The difference in minimal importance difference units (MID unit) was understood worst. Respondents also found CER and EER to be the most useful presentation approach while they rated MID unit as the least useful. Confidence in the risk ratio ranked high, even though it was rather poorly understood.

Conclusions and clinical implications

For dichotomous outcomes, presenting the effects in terms of the CER and EER could lead to the most correct interpretation. Relative measures including the risk ratio must be supplemented with absolute measures such as the CER and EER. Effects on continuous outcomes were better understood through standardised mean differences than mean differences. These can also be supplemented by dichotomised CER and EER.
Assessment of performance and safety of Corneal Chamber hypothermic storage medium and PSS-L corneal rinsing solution in human and porcine corneas
Authors: Giurgola Laura , Rodella Umberto , Gatto Claudio , Rossi Orietta , Honisch Claudia , Ragazzi Eugenio , Ruzza Paolo , Ferrari Stefano , D'Amato Tóthová Jana
Published: February 2024

Purpose

To prove the safety and performance of the hypothermic corneal storage medium "Corneal Chamber" and the rinsing solution "PSS-L" in support of the newConformité Européenne(CE) certification process in accordance with the Medical Device Regulation.

Methods

Fifteen (n=15) human donor corneas and 11 (n=11) porcine corneas were evaluated for the following parameters: endothelial cell density (ECD) and mortality, percentage of hexagonal cells (HEX%), coefficient of cellular area variation (CV%) and corneal transparency at Day 0 and after 14±1 days of storage in Corneal Chamber medium at 2–8°C. Then, the same parameters were assessed after rinsing of corneas in PSS-L for 1 min at room temperature. Evaluation of gentamicin sulfate carryover after corneal storage and PSS-L rinsing was performed by ultra-high performance liquid chromatography analysis on human corneas homogenates.

Results

Human and porcine corneas stored in Corneal Chamber medium showed a good overall quality of the tissue according to the quality parameters evaluated. In particular, mean ECD, HEX% and CV% did not show statistically significant changes at the end of storage and endothelial mortality increased to 3.1±3.3 and 7.8±3.5% in human and porcine corneas, respectively. Tissue rinsing with PSS-L did not affect the quality parameters evaluated before and gentamicin sulfate residues were absent in human corneas.

Conclusions

Corneal preservation in Corneal Chamber medium at 2–8°C for 14 days and the corneal rinse with PSS-L are safe and effective procedures allowing the preservation of the corneal quality parameters as well as the complete elimination of gentamicin sulfate from the tissues before transplantation.Cite Now
Initiative to improve handover notes in a tertiary psychiatric hospital
Authors: Ying Jiangbo , Zhang Melvyn Weibin , Tan Giles Ming Yee , Low Lambert , Fang Tina
Published: February 2024

Clinical handover is an important process in hospital settings, but it is often carried out inadequately, posing potentially serious consequences for the patients. This project aimed to increase the effectiveness of handover notes when patients were transferred between a general psychiatric ward and other wards in a tertiary psychiatric hospital. Effective handover notes in this project were defined to have the following five components: brief psychiatric history, reason for the patient to be transferred, significant risk issues, reason for psychotropic medication change and active medical issues. Baseline measurement obtained from audits revealed that the completion rate of effective handover notes was only 27.27%, which could potentially compromise patient safety and staff work efficiency. To address this problem, a series of plan-do-study-act (PDSA) cycles was implemented to improve the handover process. The interventions included education to junior doctors, reminders to complete effective handover notes and implementation of a handover template. Following each PDSA cycle, data were gathered to assess whether an effect had been achieved and to identify ways to enhance interventions to maximise impact. After the final PDSA cycle, the percentage of effective handover notes among all transfer cases reached 90.50%. Postintervention feedback from inpatient team indicated that effective communication between different teams was ensured, and staff satisfaction and time savings were improved. This study highlights the importance of employing PDSA cycles to assess and refine interventions and the usefulness of structuring the content of key components of handover notes to obtain measurable improvements.
Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up
Authors: Ta Shengjun , Li Jing , Hsi David H , Hu Rui , Lei Changhui , Shan Bo , Li Wenxia , Wang Jing , Wang Bo , Kang Nan , Li Xiaojuan , Liu Jiani , Qi Caixia , Huang Junzhe , Han Yupeng , Ruan Fangqi , Zhang Jun , Liu Liwen
Published: February 2024

Objective

The objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics.

Methods

27 patients (age: 44.3±15.5 years; 67% men, 33% women) with severely symptomatic HOCM who underwent PIMSRA from October 2016 to September 2017 were included. Their clinical status, resting and exercise stress echocardiography, electrocardiography and cardiac MRI (CMRI) after long-term follow-up were assessed.

Results

One patient died of intracerebral haemorrhage 1 year post procedurally. The New York Heart Association class, Canadian Cardiovascular Society class and exercise-induced syncopal attacks improved significantly in 26 patients (all p<0.01). Left ventricular (LV) outflow tract gradients revealed sustained reduction (resting: from 95.0 to 9.0 mm Hg, p<0.001; post exercise: from 130.5 to 21.0 mm Hg, p<0.001). The echocardiographic evaluation revealed decreased septal thickness, LV posterior wall thickness and left atrial (LA) diameter (all p<0.001). CMRI data revealed decrease in LV mass index and LA volume index and increase in LV end-diastolic volume index and stroke volume index between baseline and long-term follow-up (all p<0.05). The global longitudinal strain of LV improved from (−11.9%±3.7%) before the procedure to (−13.1%±3.9%) at the last check (p<0.001). Malignant ventricular arrhythmia and heart failure events were not observed.

Conclusions

PIMSRA can effectively alleviate symptoms in patients with HOCM and improve their hemodynamics in the long term.

Trial registration number

NCT02888132.
First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial
Authors: Ren Shengxiang , Wang Xicheng , Han Bao-Hui , Pan Yueyin , Zhao Jun , Cheng Yufeng , Hu Sheng , Liu Tianshu , Li Yalun , Cheng Ying , Feng Jifeng , Yi Shanyong , Gu Shanzhi , Gao Shegan , Luo Yongzhong , Liu Ying , Liu Caigang , Duan Huijie , Wang Shuni , Yang Xinfeng , Fan Jia , Zhou Caicun
Published: February 2024

Background

The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial.

Methods

Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile.

Results

Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1–49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator.

Conclusion

Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation.

Trial registration number

NCT04346381.
Mechanism of chronic iatrogenic CSF leak following dural puncture-ventral dural leak: case report
Authors: Carroll Ian R , Lansinger Olivia , Do Huy M , Dodd Rob , Mahaney Kelly , Li Daphne
Published: February 2024

Background

Postdural puncture headache has been traditionally viewed as benign, self-limited, and highly responsive to epidural blood patching (EBP) when needed. A growing body of data from patients experiencing unintended dural puncture (UDP) in the setting of attempted labor epidural placement suggests a minority of patients will have more severe and persistent symptoms. However, the mechanisms accounting for the failure of EBP following dural puncture remain obscure. An understanding of these potential mechanisms is critical to guide management decisions in the face of severe and persistent cerebrospinal fluid (CSF) leak.

Case presentation

We report the case of a peripartum patient who developed a severe and persistent CSF leak unresponsive to multiple EBPs following a UDP during epidural catheter placement for labor analgesia. Lumbar MRI revealed a ventral rather than dorsal epidural fluid collection suggesting that the needle had crossed the thecal sac and punctured the ventral dura, creating a puncture site not readily accessible to blood injected in the dorsal epidural space. The location of this persistent ventral dural defect was confirmed with digital subtraction myelography, permitting a transdural surgical exploration and repair of the ventral dura with resolution of the severe intracranial hypotension.

Conclusions

A ventral rather than dorsal dural puncture is one mechanism that may contribute to both severe and persistent spinal CSF leak with resulting intracranial hypotension following a UDP.
Immunogenicity and influence on disease activity of recombinant zoster vaccine in patients with rheumatoid arthritis treated with DMARDs
Authors: Kojima Shotaro , Iwamoto Taro , Kobayashi Yoshihisa , Kato Manami , Takizawa Fumiyoshi , Ida Tomoaki , Suzuki Junya , Toda Yosuke , Miyachi Kazusa , Iwata Arifumi , Furuta Shunsuke , Ikeda Kei , Nakajima Hiroshi
Published: February 2024

Objectives

This study aimed to determine the immunogenicity and the influence on disease activity of an adjuvanted recombinant varicella-zoster virus (VZV) subunit vaccine (RZV) in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs).

Methods

This prospective longitudinal study enrolled 53 patients with RA (aged ≥50 years) treated with DMARDs (conventional synthetic (cs)DMARDs 20, biological (b)DMARDs 23 and targeted synthetic (ts)DMARDs 10) and 10 control individuals. The participants received two intramuscular RZV 2 months apart. VZV-specific CD4+T cell responses (cell-mediated immunity; CMI) and IgG antibody responses (humoral immunity; HI) were assessed at 0 and 3 months after the first RZV administration using flow cytometry and enzyme immunoassay, respectively. Disease activity (Disease Activity Score 28-C reactive protein and Clinical Disease Activity Index), flares and adverse events were monitored for 6 months after the first vaccination.

Results

VZV-specific CMI and HI significantly increased in the three DMARDs-treated patients with RA after RZV administration compared with the corresponding prevaccination values (p<0.001–0.014), and the magnitudes and fold-increases of those responses were not significantly different among the three DMARDs-treated patients with RA. Furthermore, the vaccine response rates of CMI and HI were not significantly different between csDMARDs-treated patients and b-DMARDs or ts-DMARDs-treated patients. Meanwhile, no significant increases in disease activity indices or adverse events were observed in these patients during the 6-month follow-up period after the first vaccination. RZV-induced RA flares occurred in two patients (3.8%) but were mild and controllable.

Conclusion

RZV is robustly immunogenic and has a clinically acceptable safety profile in elderly patients with RA receiving DMARDs.
Improved childhood asthma control after exposure reduction interventions for desert dust and anthropogenic air pollution: the MEDEA randomised controlled trial
Authors: Kouis Panayiotis , Galanakis Emmanouil , Michaelidou Eleni , Kinni Paraskevi , Michanikou Antonis , Pitsios Constantinos , Perez Julietta , Achilleos Souzana , Middleton Nicos , Anagnostopoulou Pinelopi , Dimitriou Helen , Revvas Efstathios , Stamatelatos Gerasimos , Zacharatos Haris , Savvides Chrysanthos , Vasiliadou Emily , Kalivitis Nikos , Chrysanthou Andreas , Tymvios Filippos , Papatheodorou Stefania I , Koutrakis Petros , Yiallouros Panayiotis K
Published: February 2024

Introduction

Elevated particulate matter (PM) concentrations of anthropogenic and/or desert dust origin are associated with increased morbidity among children with asthma.

Objective

The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches randomised controlled trial assessed the impact of exposure reduction recommendations, including indoor air filtration, on childhood asthma control during high desert dust storms (DDS) season in Cyprus and Greece.

Design, participants, interventions and setting

Primary school children with asthma were randomised into three parallel groups: (a) no intervention (controls); (b) outdoor intervention (early alerts notifications, recommendations to stay indoors and limit outdoor physical activity during DDS) and (c) combined intervention (same as (b) combined with indoor air purification with high efficiency particulate air filters in children’s homes and school classrooms. Asthma symptom control was assessed using the childhood Asthma Control Test (c-ACT), spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)) and fractional exhaled nitric oxide (FeNO).

Results

In total, 182 children with asthma (age; mean=9.5, SD=1.63) were evaluated during 2019 and 2021. After three follow-up months, the combined intervention group demonstrated a significant improvement in c-ACT in comparison to controls (β=2.63, 95% CI 0.72 to 4.54, p=0.007), which was more profound among atopic children (β=3.56, 95% CI 0.04 to 7.07, p=0.047). Similarly, FEV1% predicted (β=4.26, 95% CI 0.54 to 7.99, p=0.025), the need for any asthma medication and unscheduled clinician visits, but not FVC% and FeNO, were significantly improved in the combined intervention compared with controls.

Conclusion

Recommendations to reduce exposure and use of indoor air filtration in areas with high PM pollution may improve symptom control and lung function in children with asthma.

Trial registration number

NCT03503812.
Temporal effective stress response of soil elements below the base of an excavation in sensitive clay
Authors: Tornborg Johannes , Karlsson Mats , Dijkstra Jelke
Published: February 2024

Investigations into the temporally evolving stress state below the base of excavations and underground structures are very scarce, in contrast to studies of horizontal earth pressures during the construction stage. Therefore in this work, the measured temporal response in terms of vertical and horizontal effective stresses and displacements below a tunnel slab at the base of an excavation located in a deep sensitive clay deposit is reported. In addition to the measured unloading response over time, the completeness of the site description and complementary measurements enables future benchmarking of numerical models at boundary and element level. Instrument clusters of earth pressure cells and piezometers were installed at three locations in one cross-section. The monitoring data allow the interpretation of effective stress paths and stress ratios, K = [Formula: see text]/[Formula: see text], at soil element level covering the construction and the serviceability stages. The in situ stress ratios enable a unique comparison to prior laboratory studies of K during unloading. The data presented herein on the evolution of K corroborate, although approximately, previous studies at laboratory scale. Furthermore, at system level, the monitoring data reveal the intricate interplay between deformations resulting from excavation and pile driving.
Generic multi-particle transverse momentum correlations as a new tool for studying nuclear structure at the energy frontier
Authors: Dahlbæk Nielsen Emil Gorm , Rømer Frederik K. , Gulbrandsen Kristjan , Zhou You
Published: February 2024

The mean transverse momentum of produced particles, $$[p_\textrm{T} ]$$

[

p
T

]

, and its event-by-event fluctuations give direct access to the initial conditions of ultra-relativistic heavy-ion collisions and help probe the colliding nuclei’s structure. The $$[p_\textrm{T} ]$$

[

p
T

]

fluctuations can be studied via multi-particle $$p_\textrm{T}$$

p
T

correlations; so far, only the lowest four orders have been studied. Higher-order fluctuations can provide stronger constraints on the initial conditions and improved sensitivity to the detailed nuclear structure; however, their direct implementation can be challenging and is still lacking. In this paper, we apply a generic recursive algorithm for the genuine multi-particle $$p_\textrm{T}$$

p
T

correlations, which enables the accurate study of higher-order $$[p_\textrm{T} ]$$

[

p
T

]

fluctuations without heavy computational cost for the first time. With this algorithm, we will examine the power of multi-particle $$p_\textrm{T}$$

p
T

correlations through Monte Carlo model studies with different nuclear structures. The impact on the nuclear structure studies, including the nuclear deformation and triaxial structure, will be discussed. These results demonstrate the usefulness of multi-particle $$p_\textrm{T}$$

p
T

correlations for studying nuclear structure in high-energy nuclei collisions at RHIC and the LHC, which could serve as a complementary tool to existing low-energy nuclear structure studies.
MULTIFRACTAL CHARACTERIZATION OF THE INHOMOGENEOUS STRAIN EVOLUTION OF THE DEHYDRATED COAL: INSIGHT FROM COAL MICROSTRUCTURE
Authors: FENG JUNJUN , XU CHUANHUA , YU FENG , PENG JUN , HUANG QISONG , JIN PENG
Published: February 2024

Underground coal mining in China has gradually moved into deeper seams in recent years, which results in a higher ambient temperature in the mining space and significantly affects the mechanical behavior of coal. In this study, dehydrated coal samples were obtained at different temperatures ranging from 30[Formula: see text] to 70[Formula: see text], and the mechanical behavior of the dehydrated coal was investigated through compressive loading tests. The digital image correlation (DIC) method was used to acquire the strain field of coal, and a multifractal analysis was conducted to characterize the strain evolution of coal. The findings suggest that the increasing temperatures result in higher moisture desorption rates and greater volumetric contraction strain in coal. Furthermore, coal with higher moisture desorption exhibits higher peak stress and peak strains when subjected to compressive loading. The multifractal analysis of the inhomogeneous strain evolution indicates a gradual decrease in the parameter [Formula: see text] under compressive loading, followed by a sudden increase before reaching the failure point due to strain localization. The multifractal mechanism was further investigated, revealing that the inhomogeneous strain field of coal is inherently affected by the microstructure of coal. In addition, a mathematical model was proposed to elucidate the relationship between the inhomogeneous coal strain and the microstructure of coal. The result indicates that the inhomogeneity of the coal strain is directly associated with the multifractal singularity of the coal microstructure. Finally, the feasibility of using the multifractal parameter [Formula: see text] to identify coal strain localization has been demonstrated, indicating its potential value in aiding engineers to determine the SLZ in deep coal mines.
Hardness determination by a semi-automatic testing system
Authors: Jain Preeti , Shinde Sachin Manohar , Panchikattil Susheelkumar , Diwan Mohit
Published: February 2024

The hardness testing is vital for metals for testing and production quality control. Hardness testing is a fine indicator to determine the mechanical characteristics of metals. The various types of hardness testing methods include Rockwell, Vicker, Brinell, and Knoop testing methods. The most prevalent manual method to determine hardness is indentation using dead weight technology. However, the said technology is quite ancient and it has its own limitations, like the kinetic effect applying excessive load at actual, man-to-man variations, variation over the period due to deterioration and friction effects of moving parts like lever, weight block hanger, etc. increases the uncertainty of this method and eventually demands for upgradation of the technology. Further, the methods currently in use are open-loop and manually operated testers. The main drawback of all these testers is that they provide zero feedback, and so the obtained result needs to be compared to the desired result. To overcome the above-stated problem, the paper presents some novel modifications for measuring hardness using existing methods of Rockwell, Vicker, and Brinell testing. Toward this objective, the paper proposes to modify existing testers and develop a semiautomatic hardness testing system. Firstly, for Rockwell testing, the work aims to design a closed-loop system for hardness testing. The proposed system comprises of Arduino as an open microcontroller, a load cell along with servo motor, and its driver to establish the desired closed loop. The need of obtaining a more accurate result, free from human interference gives rise to a closed-loop system for hardness testing. The key aspect of the closed-loop system lies in retaining the basic structure of the metal. Unlike traditional hardness tester, during testing, the weight increases gradually, due to which the basic structure of metal is not deformed. Secondly, the paper proposes a computational methodology that would estimate the Vickers and Brinell hardness value. The proposed system comprises of a camera for gathering hardness indentation images, thereby automating the system. Further, these images are analyzed based on image processing software, and the indentation depth is obtained. The proposed work thus replaces human intervention to calculate the hardness of the material. The results obtained based on the proposed systems provide a proof of concept to address the problems of traditional Rockwell, Vicker, and Brinell testing.
Natural fracture density controls productivity in shale reservoirs
Authors: Kurison Clay , Woldeamanuel Mandefro B.
Published: February 2024

Shale reservoirs host ubiquitous multi-scale natural fractures created by factors such as pore pressure build-up after petroleum generation and palaeo crustal stress changes during tectonic episodes. Natural fractures are among postulated drivers of stimulated shale well productivity and related variability. Quantifying the aforementioned role and optimizing recovery call for litho-structural assessments. In this interdisciplinary study, natural fracture density (fractures per unit length) for North and South American shales (Marcellus, Eagle Ford, Haynesville, Barnett, Fayetteville and Vaca Muerta) was estimated from published observations of outcrops, cores and borehole images. Associated production for the latest horizontal wells, drilled in the most productive locations (sweet spots), was normalized by lateral length and reservoir thickness. It was found to correlate positively with the density of small-scale natural fractures. Durations of transient linear flow, diagnosed from production data, were play-specific, negatively correlated with small-scale natural fracture density and led to realization of picodarcy matrix permeability. Conversely, large-scale (tectonic) fractures limit stimulation efficiency and pose environmental/induced seismicity risks. Therefore, stimulation-driven reactivation of small-scale fractures facilitates drainage and enhances well productivity. Relatedly, reservoir flow regimes and production decline curves are intricately controlled by interplay of natural fracture density and matrix permeability. Variability of these parameters calls for acreage-tailored stimulations.
Innovation Is Overrated: A Provocation
Authors: Blancato Filippo Gualtiero
Published: February 2024

Digital innovation is not working in the interest of the whole of society. It is time to radically rethink its purpose without sacrificing the benefits it entails.
Co-Developing Programs and Their Proof of Correctness
Authors: Chapman Roderick , Dross Claire , Matthews Stuart , Moy Yannick
Published: February 2024

The SPARK programming language and analyzer.
Software Managers' Guide to Operational Excellence
Authors: Matsudaira Kate
Published: February 2024

The secret to being a great engineering leader? Setting up the right checks and balances.
Measuring GitHub Copilot's Impact on Productivity
Authors: Ziegler Albert , Kalliamvakou Eirini , Li X. Alice , Rice Andrew , Rifkin Devon , Simister Shawn , Sittampalam Ganesh , Aftandilian Edward
Published: February 2024

Case study asks Copilot users about its impact on their productivity, and seeks to find their perceptions mirrored in user data.
Leaf Vein Patterning
Authors: Scarpella Enrico
Published: February 2024

Leaves form veins whose patterns vary from a single vein running the length of the leaf to networks of staggering complexity where huge numbers of veins connect to other veins at both ends. For the longest time, vein formation was thought to be controlled only by the polar, cell-to-cell transport of the plant hormone auxin; recent evidence suggests that is not so. Instead, it turns out that vein patterning features are best accounted for by a combination of polar auxin transport, facilitated auxin diffusion through plasmodesma intercellular channels, and auxin signal transduction—though the latter's precise contribution remains unclear. Equally unclear remain the sites of auxin production during leaf development, on which that vein patterning mechanism ought to depend. Finally, whether that vein patterning mechanism can account for the variety of vein arrangements found in nature remains unknown. Addressing those questions will be the exciting challenge of future research.
Deep Learning in Image-Based Plant Phenotyping
Authors: Murphy Katherine M. , Ludwig Ella , Gutierrez Jorge , Gehan Malia A.
Published: February 2024

A major bottleneck in the crop improvement pipeline is our ability to phenotype crops quickly and efficiently. Image-based, high-throughput phenotyping has a number of advantages because it is nondestructive and reduces human labor, but a new challenge arises in extracting meaningful information from large quantities of image data. Deep learning, a type of artificial intelligence, is an approach used to analyze image data and make predictions on unseen images that ultimately reduces the need for human input in computation. Here, we review the basics of deep learning, assessments of deep learning success, examples of applications of deep learning in plant phenomics, best practices, and open challenges.
Chemical Kinetics in Microdroplets
Authors: Wilson Kevin R. , Prophet Alexander M.
Published: February 2024

Micrometer-sized compartments play significant roles in driving heterogeneous transformations within atmospheric and biochemical systems as well as providing vehicles for drug delivery and novel reaction environments for the synthesis of industrial chemicals. Many reports now indicate that reaction kinetics are accelerated under microconfinement, for example, in sprays, thin films, droplets, aerosols, and emulsions. These observations are dramatic, posing a challenge to our understanding of chemical reaction mechanisms with potentially significant practical consequences for predicting the complex chemistry in natural systems. Here we introduce the idea of kinetic confinement, which is intended to provide a conceptual backdrop for understanding when and why microdroplet reaction kinetics differ from their macroscale analogs.
From Foes to Friends: The Causes of Interstate Rapprochement and Conciliation
Authors: Mattes Michaela , Weeks Jessica L.P.
Published: February 2024

When, why, and how do countries move from hostile to peaceful relations, and sometimes even friendship? We draw on the interstate peace literature to identify two peace processes. Rapprochement represents a first step during which enemies might develop normal working relations. Some states then progress to conciliation and establish warm and cooperative ties. We compare rapprochement to conciliation, outline the mechanisms that drive each process, and review scholarly findings about three types of causal variables: abrupt shocks, stable contextual factors, and policy initiatives. A key insight emerges that conciliation is not simply an extension of rapprochement—the predictors of these two processes differ significantly. We then call for greater scholarly attention to the study of conciliation, interactions of causal factors, the domestic politics underlying each process, the causes of peace failure, and empirical and methodological challenges.
Organizing and Democracy: Understanding the Possibilities for Transformative Collective Action
Authors: Han Hahrie , Baggetta Matthew , Oser Jennifer
Published: February 2024

Democracy requires collective action—but not all forms of collective action are the same. Scholars need a more coherent intellectual infrastructure to differentiate distinct forms of collective action and to identify the kinds of collective action that enable democracy. We distinguish between two types of collective action: organizing, which seeks to transform individuals and groups into effective agents who can shape public outcomes, and mobilizing, which seeks to aggregate and articulate preferences in the public sphere with no explicit focus on individual or organizational change. We review work identifying the dimensions of possible transformation at the micro, meso, and macro levels, and existing evidence for it. We urge scholars to study organizing separate from (and in comparison to) mobilizing and suggest possible research strategies and questions. In doing so, we aim to provide a foundation for future research on organizing and its relationship to democracy.