bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets’ attainment in subjects with and without type 2 diabetes
Authors: Morieri Mario Luca , Perrone Valentina , Veronesi Chiara , Degli Esposti Luca , Andretta Margherita , Plebani Mario , Fadini Gian Paolo , Vigili de Kreutzenberg Saula , Avogaro Angelo
Published: July 2021

Background

This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients.

Methods

We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone.

Results

We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78–100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from − 3 to − 11%, p < 0.001, HIS + ezetimibe vs. HIS—from − 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a “treat to absolute LDL-cholesterol levels” approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention.

Conclusions

Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention.
Association between triglyceride-glucose index and risk of arterial stiffness: a cohort study
Authors: Wu Shouling , Xu Luli , Wu Mingyang , Chen Shuohua , Wang Youjie , Tian Yaohua
Published: July 2021

Background

Triglyceride–glucose (TyG) index, a simple surrogate marker of insulin resistance, has been reported to be associated with arterial stiffness. However, previous studies were limited by the cross-sectional design. The purpose of this study was to explore the longitudinal association between TyG index and progression of arterial stiffness.

Methods

A total of 6028 participants were derived from the Kailuan study. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Arterial stiffness progression was assessed by the annual growth rate of repeatedly measured baPWV. Multivariate linear regression models were used to estimate the cross-sectional association of TyG index with baPWV, and Cox proportional hazard models were used to investigate the longitudinal association between TyG index and the risk of arterial stiffness.

Results

Multivariate linear regression analyses showed that each one unit increase in the TyG index was associated with a 39 cm/s increment (95%CI, 29–48 cm/s, P < 0.001) in baseline baPWV and a 0.29 percent/year increment (95%CI, 0.17–0.42 percent/year, P < 0.001) in the annual growth rate of baPWV. During 26,839 person-years of follow-up, there were 883 incident cases with arterial stiffness. Participants in the highest quartile of TyG index had a 58% higher risk of arterial stiffness (HR, 1.58; 95%CI, 1.25–2.01, P < 0.001), as compared with those in the lowest quartile of TyG index. Additionally, restricted cubic spline analysis showed a significant dose–response relationship between TyG index and the risk of arterial stiffness (P non-linearity = 0.005).

Conclusion

Participants with a higher TyG index were more likely to have a higher risk of arterial stiffness. Subjects with a higher TyG index should be aware of the following risk of arterial stiffness progression, so as to establish lifestyle changes at an early stage.
Factors influencing phagocytosis of malaria parasites: the story so far
Authors: Chua Caroline Lin Lin , Ng Ida May Jen , Yap Bryan Ju Min , Teo Andrew
Published: July 2021

There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.
Socio-cultural factors for breastfeeding cessation and their relationship with child diarrhoea in the rural high-altitude Peruvian Andes – a qualitative study
Authors: Nuño Martínez Néstor , Wallenborn Jordyn , Mäusezahl Daniel , Hartinger Stella M. , Muela Ribera Joan
Published: July 2021

Background

In some areas of the world, breast milk is seen as a potential source of child diarrhoea. While this belief has been explored in African and Southeast Asian countries, it remains vastly understudied in Latin American contexts. We investigate socio-cultural factors contributing to breastfeeding cessation in rural high-altitude populations of the Peruvian Andes. The role of socio- cultural factors in the local explanatory model of child diarrhoea, and whether these perceptions were integrated in the local healthcare system were assessed.

Methods

Within the framework of a randomised controlled trial, we conducted semi-structured interviews with 40 mothers and 15 health personnel from local healthcare centres involved in the trial.

Results

Cultural beliefs on breastfeeding cessation included the perception that breast milk turned into “blood” after six months and that breastfeeding caused child diarrhoea. We identified eight local types of child diarrhoea, and women linked six of them with breastfeeding practices. “Infection” was the only diarrhoea mothers linked to hygiene and the germ disease concept and perceived as treatable through drug therapy. Women believed that other types of diarrhoea could not be treated within the formal healthcare sector. Interviews with health personnel revealed no protocol for, or consensus about, the integration of the local explanatory model of child diarrhoea in local healthcare and service provision.

Conclusions

The local explanatory model in rural Andean Peru connected breastfeeding with child diarrhoeas. Cultural beliefs regarding diarrhoea management may increase home treatments, even in cases of severe diarrhoeal episodes. Future national breastfeeding support programmes should promote peer-counselling approaches to reduce negative attitudes towards breastfeeding and health practitioners. Local explanatory models should be incorporated into provincial and regional strategies for child diarrhoea management to promote equity in health and improve provider-patient relationships.
Examining the role of government in shaping disability inclusiveness around COVID-19: a framework analysis of Australian guidelines
Authors: Colon-Cabrera David , Sharma Shivika , Warren Narelle , Sakellariou Dikaios
Published: July 2021

Background

The COVID-19 pandemic has uncovered the ways in which disabled people are made more vulnerable due to structural inequalities. These vulnerabilities are the result of the interaction between individual and structural factors that shape how risk is experienced by disabled people. In Australia, these vulnerabilities are influenced by the way disability services and care for disabled people are delivered through a consumer-directed approach. We analysed the policies and documentation made by the Australian Government and state and territory governments during the pandemic to explore whether these were disability-inclusive. We aimed to unpack how these policies shaped disabled people as vulnerable citizens.

Methods

Guided by documentary research, we used framework analysis to examine the policies of the Australian Government and state and territory governments. We analysed legislation that was given royal assent by the federal, state and territory governments, and documents (reports, fact sheets, guidance documents, etc.) published by the federal government and the state of Victoria (given that this state experienced the brunt of the epidemic in Australia) between February 2020 to August of 2020.

Results

We found that most of the resources were not aimed at disabled people, but at carers and workers within disability services. In addition, most policies formulated by the Australian Government were related to the expansion of welfare services and the creation of economic stimulus schemes. However, while the stimulus included unemployed people, the expansion of benefits explicitly excluded disabled people who were not employed. Most of the legislation and documents offered accessibility options, though most of these options were only available in English. Disability oriented agencies offered more extensive accessibility options.

Conclusions

The findings indicate a large number of documents addressing the needs of disabled people. However, disability-inclusiveness appeared to be inconsistent and not fully considered, leaving disabled people exposed to greater risk of COVID-19. Neoliberal policies in the health and welfare sector in Australia have led to an individualisation of the responsibility to remain healthy and a reliance on people as independent consumers. Governments need to take a clear stance towards the emergence of such a discourse that actively disvalues disabled people.
The immune checkpoint regulator PD-L1 expression are associated with clinical progression in prostate cancer
Authors: He Juan , Yi Min , Tan Lingfeng , Huang Jianghua , Huang Lin
Published: July 2021

Background

The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown positive efficacy in several solid cancers due to their targeted antitumour effects. However, the frequency and clinical implication value in prostate cancer still remain unclear.

Methods

The PD-1/PD-L1 expression was detected by immunohistochemical (IHC) analysis in 96 retrospectively collected cases of prostatic cancer and 44 controls of benign prostatic hyperplasia (BPH). Its correlation with clinicopathological features including age, PSA level, Gleason score, lymph node metastasis, clinical T stage and risk factor grade in prostate cancer was also assessed.

Results

The PD-L1-positive expression was significantly higher in cancer cases compared with benign tissues, whereas no difference in PD-1 positive expression was found. Moreover, the PD-L1 expression in tumour cells or lymphocytes was associated with Gleason score, but not related to age, preoperative PSA level, clinical T-stage, lymph node metastasis and grade of risk factors. In addition, no association between the positive expression of PD-1 and PD-L1 in tumour cells and lymphocytes was found.

Conclusions

The expression of PD-L1 not PD-1 is highly prevalent in prostate cancer. PD-L1 is closely related to Gleason score and may be a co-factor associated with the progression of prostate cancer.
A method for measuring time spent in bradykinesia and dyskinesia in people with Parkinson’s disease using an ambulatory monitor
Authors: Khodakarami Hamid , Shokouhi Navid , Horne Malcolm
Published: July 2021

Background

Fluctuations in motor function in Parkinson’s Disease (PD) are frequent and cause significant disability. Frequently device assisted therapies are required to treat them. Currently, fluctuations are self-reported through diaries and history yet frequently people with PD do not accurately identify and report fluctuations. As the management of fluctuations and the outcomes of many clinical trials depend on accurately measuring fluctuations a means of objectively measuring time spent with bradykinesia or dyskinesia would be important. The aim of this study was to present a system that uses wearable sensors to measure the percentage of time that bradykinesia or dyskinesia scores are above a target as a means for assessing levels of treatment and fluctuations in PD.

Methods

Data in a database of 228 people with Parkinson’s Disease and 157 control subjects, who had worn the Parkinson’s Kinetigraph ((PKG, Global Kinetics Corporation™, Australia) and scores from the Unified Parkinson’s Disease Rating Scale (UPDRS) and other clinic scales were used. The PKG’s provided score for bradykinesia and dyskinesia every two minutes and these were compared to a previously established target range representing a UPDRS III score of 35. The proportion of these scores above target over the 6 days that the PKG was worn were used to derive the percent time in bradykinesia (PTB) and percent time in dyskinesia (PTD). As well, a previously describe algorithm for estimating the amplitude of the levodopa response was used to determine whether a subject was a fluctuator or non-fluctuator.

Results

Using this approach, a normal range of PTB and PTD based on Control subject was developed. The level of PTB and PTD experienced by people with PD was compared with their levels of fluctuation. There was a correlation (Pearson’s ρ = 0.4) between UPDRS II scores and PTB: the correlation between Parkinson Disease Questionnaire scores and UPDRS Total scores and PTB and slightly lower. PTB and PTD fell in response to treatment for bradykinesia or dyskinesia (respectively) with greater sensitivity than clinical scales.

Conclusions

This approach provides an objective assessment of the severity of fluctuations in Parkinson’s Disease that could be used in in clinical trials and routine care.
Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in postmenopausal osteoporosis
Authors: Diao Weiyi , Wang Yongguang , Zhang Jun , Shao Haiyu , Huang Yazeng , Jin Mengran
Published: July 2021

Background

Circular RNAs (circRNAs) are emerging as crucial regulators in various human diseases. So far, the expression profile and regulatory mechanism of circRNAs in postmenopausal osteoporosis (PMOP) are less studied and should be deciphered urgently. Herein, we aimed to reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions.

Methods

To reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions, whole transcriptome sequencing and bioinformatics analysis were performed to identify differentially expressed circRNAs (DECs). The expression pattern and regulatory networks of DECs in peripheral blood mononuclear cells (PBMCs) were unearthed.

Results

A total of 373 DECs comprising 123 intronic, 100 antisense, 70 exonic, 55 intergenic, and 25 sense-overlapping circRNAs were identified. Among these, 73 circRNAs were upregulated and 300 were downregulated. These DECs exerted pivotal functions in the pathogenesis of PMOP as demonstrated by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The circRNA-miRNA-mRNA co-expression network comprising 28 DECs, 145 miRNAs, and 175 differentially expressed mRNAs predicted the possible mechanism of the pathogenesis and progression of PMOP.

Conclusion

The results of the present study provided a further comprehension of circRNA-associated competing endogenous RNA regulatory mechanism in PMOP. The steadily expressed and disease-specific DECs may serve as promising diagnostic and prognostic biomarkers for PMOP.
Neutrophil Extracellular Traps: A New Player in Cancer Metastasis and Therapeutic Target
Authors: Yang Dakai , Liu Jing
Published: July 2021

Neutrophil Extracellular Traps (NETs) are neutrophil-derived extracellular scaffolds, which typically consist of fibrous decondensed chromatins decorated with histones and granule proteins. Initially discovered as a host defence mechanism of neutrophil against pathogens, they have also been implicated in the progression of sterile inflammation-associated diseases such as autoimmune disease, diabetes, and cancer. In this review, we highlight and discuss the more recent studies on the roles of NETs in cancer development, with a special focus on cancer metastasis. Moreover, we present the strategies for targeting NETs in pre-clinical models, but also the challenging questions that need to be answered in the field.
The genetic architecture of temperature adaptation is shaped by population ancestry and not by selection regime
Authors: Otte Kathrin A. , Nolte Viola , Mallard François , Schlötterer Christian
Published: July 2021

Background

Understanding the genetic architecture of temperature adaptation is key for characterizing and predicting the effect of climate change on natural populations. One particularly promising approach is Evolve and Resequence, which combines advantages of experimental evolution such as time series, replicate populations, and controlled environmental conditions, with whole genome sequencing. Recent analysis of replicate populations from two differentDrosophila simulansfounder populations, which were adapting to the same novel hot environment, uncovered very different architectures—either many selection targets with large heterogeneity among replicates or fewer selection targets with a consistent response among replicates.

Results

Here, we expose the founder population from Portugal to a cold temperature regime. Although almost no selection targets are shared between the hot and cold selection regime, the adaptive architecture was similar. We identify a moderate number of targets under strong selection (19 selection targets, mean selection coefficient = 0.072) and parallel responses in the cold evolved replicates. This similarity across different environments indicates that the adaptive architecture depends more on the ancestry of the founder population than the specific selection regime.

Conclusions

These observations will have broad implications for the correct interpretation of the genomic responses to a changing climate in natural populations.
An Internet-based emotion regulation intervention versus no intervention for non-suicidal self-injury in adolescents: a statistical analysis plan for a feasibility randomised clinical trial
Authors: Olsen Markus Harboe , Morthorst Britt , Pagsberg Anne Katrine , Heinrichsen Michella , Møhl Bo , Rubæk Lotte , Bjureberg Johan , Simonsson Olivia , Lindschou Jane , Gluud Christian , Jakobsen Janus Christian
Published: July 2021

Background

Non-suicidal self-injury (NSSI) has a lifetime prevalence of 17% in adolescents in the general population and up to 74% in adolescents with psychiatric disorders. NSSI is one of the most important predictors of later suicidal behaviour and death by suicide. The TEENS feasibility trial was initiated to assess the feasibility and safety of Internet-based Emotion Regulation Individual Therapy for Adolescents (ERITA) as an add-on to treatment as usual in 13–17-year-old patients with NSSI referred to the Child and Adolescent Mental Health Services.

Methods

The TEENS feasibility trial is a randomised clinical trial with a parallel-group design. The trial intervention is an 11-week online therapy which is tested as an add-on to treatment as usual versus treatment as usual. The primary feasibility outcomes are the fraction of participants who (1) completed 12 weeks of follow-up interview or assessment, (2) consented to inclusion and randomisation out of all eligible participants, and (3) were compliant with the experimental intervention, assessed as completion of at least six out of eleven modules in the programme. Since this is a feasibility trial, we did not predefine a required sample size. The exploratory clinical outcome, the frequency of NSSI episodes, assessed using Deliberate Self-Harm Inventory – Youth version (DSHI-Y), at the end of intervention, is planned to be the future primary outcome in a larger pragmatic definitive randomised clinical trial. After completion of the feasibility trial, blinded data will be analysed by two independent statisticians blinded to the intervention, where ‘A’ and ‘B’ refer to the two groups. A third party will compare these reports, and discrepancies will be discussed. The statistical report with the analyses chosen for the manuscript is being tracked using a version control system, and both statistical reports will be published as a supplementary material. Based on the final statistical report, two blinded conclusions will be drawn by the steering group.

Discussion

We present a pre-defined statistical analysis plan for the TEENS feasibility trial, which limits bias, p-hacking, data-driven interpretations. This statistical analysis plan is accompanied by a pre-programmed version-controlled statistical report with simulated data, which increases transparency and reproducibility.

Trial registration

ClinicalTrials.govNCT04243603. Registered on 28 January 2020
Moderate-intensity exercise versus high-intensity interval training to recover walking post-stroke: protocol for a randomized controlled trial
Authors: Miller Allison , Reisman Darcy S. , Billinger Sandra A. , Dunning Kari , Doren Sarah , Ward Jaimie , Wright Henry , Wagner Erin , Carl Daniel , Gerson Myron , Awosika Oluwole , Khoury Jane , Kissela Brett , Boyne Pierce
Published: July 2021

Background

Stroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training.

Methods

Using a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40–80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training.

Discussion

This study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke.

Trial registration

ClinicalTrials.govNCT03760016. Registered on November 30, 2018.
Stakeholder perspectives on barriers and enablers to recruiting anxious children undergoing day surgery under general anaesthetic: a qualitative internal pilot study of the MAGIC randomised controlled trial
Authors: Kettle Jennifer , Deery Chris , Bolt Robert , Papaioannou Diana , Marshman Zoe
Published: July 2021

Abstract

Background

The ‘Melatonin for Anxiety prior to General anaesthesia In Children’ (MAGIC) trial was designed to compare midazolam and melatonin as pre-medications for anxious children (aged five to fourteen), undergoing day-case surgical procedures under general anaesthesia. Low recruitment is a challenge for many trials, particularly paediatric trials and those in ‘emergency’ settings. A qualitative study as part of MAGIC aimed to gather stakeholder perspectives on barriers and enablers to recruitment.

Methods

Sixteen stakeholders from six sites participated in semi-structured interviews about their experiences of setting up the MAGIC trial and recruiting patients as part of the internal pilot. Data was analysed using framework analysis.

Results

Participants identified barriers and enablers to recruitment. Barriers and enablers related to the study, participants, the population of anxious children, practitioners, collaboration with other health professionals, ethics, specific settings and the context of surgical day units and the wider health system. Attempting to recruit anxious children from a surgical day unit is particularly challenging for several reasons. Issues include the practicalities of dealing with a child experiencing anxiety for parents/guardians; professional unwillingness to make things more difficult for families and clinicians and nurses valuing predictability within a busy and time-sensitive setting.

Conclusions

Multi-site RCTs face recruitment barriers relating to study-wide and site-specific factors. There are multiple barriers to recruiting anxious children due to undergo day-case surgery. Barriers across domains can interrelate and reinforce each other, reflecting challenges relating to populations and settings. For example, in the case of anxious children, parents and other health professionals are concerned about exacerbating children’s anxiety prior to surgery. They may look for ways to keep things predictable and avoid the uncertainty of an RCT. Pre-trial engagement work could help address concerns among collaborating health professionals.

Using rapid ethnography during set-up or an internal pilot to focus on how the protocol will be or has been operationalised in practice may help identify issues. Allowing time to reflect on the findings of internal pilots and implement necessary changes could facilitate higher recruitment during the main phase of a trial.

Trial registration

NIHR Trial Registration Number: ISRCTN18296119. Registered on October 01, 2019.
Effects of a low-dose IL-2 treatment in HLA-B27 transgenic rat model of spondyloarthritis
Authors: Araujo L. M. , Jouhault Q. , Fert I. , Bouiller I. , Chiocchia G. , Breban M.
Published: July 2021

Introduction/Aim

HLA-B27/human β2m transgenic rats (B27-rats) develop an inflammatory disorder resembling spondyloarthritis (SpA) with dysregulated IL-10/IL-17 production by regulatory T cells (Treg). Treg plays a major role in controlling pathogenic inflammatory processes. Interleukin 2 (IL-2), a cytokine which promotes Treg cell survival and function, may thus have therapeutic efficacy in SpA. Here, we tested this hypothesis using a low dose of IL-2 treatment in B27-rat.

Material and methods

B27-rats aged 4 weeks (before disease onset) and nontransgenic (NTG) littermates were administered intraperitoneally recombinant human IL-2 (Sanofi®; 2,000IU/injection) or PBS, 3 days per week during 6 weeks. Assessment of treatment effect was performed, based on clinical (weight, diarrhea, arthritis), histological (proximal and distal colon, caecum, ileum and tarsal/ankle joint) scores, and frequency of Treg in the spleen and lymph nodes (LN).

Results

IL-2 administration had no effect on weight gain, either in B27- or NTG-rats. Over the 6 weeks of treatment, the clinical disease score worsened similarly in both IL-2-treated and control groups of B27-rats. The macroscopic and histological evaluation of gut and joints showed marked inflammation in B27-rats; however, no change related to IL-2 treatment was observed. In the B27-rats, the percentage of Treg was moderately increased after IL-2 treatment in the spleen, but neither in mesenteric nor peripheral LN in those rats.

Conclusion

Our data demonstrate that a low dose of IL-2 administered before disease onset was moderately effective for boosting Treg but failed to prevent SpA development in B27-rat.
Severe acute respiratory syndrome coronavirus 2 reinfection in a coronavirus disease 2019 recovered young adult: a case report
Authors: Awada Hussein , Nassereldine Hasan , Hajj Ali Adel
Published: July 2021

Background

Coronavirus disease 2019 has been a public health threat and a worldwide emergency for more than a year. Unfortunately, many questions concerning the pathophysiology, management, and long-term side effects remain unanswered, and novel aspects of the disease keep on emerging. Of concern to healthcare providers are the recent reported cases of reinfection. Serum coronavirus disease 2019 antibodies have been detected within a few days after onset of the disease. However, it remains unclear whether this immune response is universal, or whether it can lead to latent immunity.

Case presentation

A previously healthy 27-year-old white man presented with fever, chills, back pain, and other constitutional symptoms, 2 days after being exposed to coronavirus disease 2019 positive patients. His severe acute respiratory syndrome coronavirus 2 polymerase chain reaction was positive, and his symptoms resolved over the next 2 weeks. One month after a confirmatory negative severe acute respiratory syndrome coronavirus 2 polymerase chain reaction, he was found to be ineligible for plasma donation as his anti-severe acute respiratory syndrome coronavirus 2 serology was negative. The patient redeveloped symptoms similar to his first infection 3 weeks after the negative serology test. He and his wife both tested positive via polymerase chain reaction. Their symptoms resolved over the next few days, and they had a negative polymerase chain reaction test 10 days after the positive polymerase chain reaction.

Conclusion

While studies showed that anti-severe acute respiratory syndrome coronavirus 2 immunoglobulins start to develop early after infection, our healthy young patient’s immune system failed to mount latent immunity against the virus. This left him, especially amid widespread social and medical misconceptions, vulnerable to reinfection by severe acute respiratory syndrome coronavirus 2. Our case disputes the timelines for immune response that were set and supported by research studies. Our case also raises questions regarding prioritizing vaccinating other individuals over those with prior infection.
Identification and characterization of miRNAs associated with sterile flower buds in the tea plant based on small RNA sequencing
Authors: Qu Hao , Liu Yue , Jiang Huibing , Liu Yufei , Song Weixi , Chen Linbo
Published: July 2021

Background

miRNAs are a type of conserved, small RNA molecule that regulate gene expression and play an important role in the growth and development of plants. miRNAs are involved in seed germination, root development, shoot apical meristem maintenance, leaf development, and flower development by regulating various target genes. However, the role of miRNAs in the mechanism of tea plant flower sterility remains unclear. Therefore, we performed miRNA sequencing on the flowers of fertile male parents, female parents, and sterile offspring.

Results

A total of 55 known miRNAs and 90 unknown miRNAs were identified. In the infertile progeny, 37 miRNAs were differentially expressed; 18 were up-regulated and 19 were down-regulated. miR156, miR157, miR164, miR167, miR169, miR2111 and miR396 family members were down-regulated, and miR160, miR172 and miR319 family members were up-regulated. Moreover, we predicted that the 37 differentially expressed miRNAs target a total of 363 genes, which were enriched in 31 biological functions. We predicted that miR156 targets 142 genes, including ATD1A, SPL, ACA1, ACA2, CKB22 and MADS2.

Conclusion

We detected a large number of differentially expressed miRNAs in the sterile tea plant flowers, and their target genes were involved in complex biological processes. Among these miRNAs, the down-regulation of miR156 may be one of the factor in the formation of sterile floral buds in tea plants.
Vertebral Fractures Occur Despite Control of Acromegaly and Are Predicted by Cortical Volumetric Bone Mineral Density
Authors: Kužma Martin , Vaňuga Peter , Ságová Ivana , Pávai Dušan , Jackuliak Peter , Killinger Zdenko , Binkley Neil , Winzenrieth Renaud , Payer Juraj
Published: July 2021

Context

Recent studies suggest that cortical bone could also play a role in vertebral fracture (VF) development in acromegaly.

Objective

Evaluate the occurrence of VFs and their relationship to dual energy x-ray absorptiometry–derived bone parameters.

Methods

A single-center 2-year prospective study of acromegaly patients was conducted. Each subject had L1-4 spine, femoral neck and total hip (TH) areal BMD measured using DXA, and trabecular bone score (TBS) measurement performed. 3D Shaper™ was used to assess proximal femur trabecular and cortical volumetric (v)BMD, cortical surface (s)BMD, and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using a semiquantitative approach. Study outcomes were assessed at 2 time points: baseline and month 24.

Results

70 acromegaly patients (34 M/36F; average 55.1 years) were studied, including 26 with active disease. In 13 patients, 9 with controlled disease, VF was observed. A decrease in TBS, sBMD, neck trabecular vBMD, TH, and neck cortical vBMD in VF compared with non-VF subjects was observed (P < .05). Multivariate analysis of fracture prediction showed TH cortical vBMD as the best fracture prediction parameter with area under the curve of 0.774. TBS was negatively associated with fasting plasma glucose and glycated hemoglobin (HBA1c) at each time point during the follow-up.

Conclusion

From the total number of 13 VF subjects, 9 were in the controlled disease group. The most sensitive and specific predictor of incident VF was TH cortical vBMD, suggesting that cortical bone is involved in fracture development.
Clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins and preimplantation development
Authors: Morita Akihito , Satouh Yuhkoh , Kosako Hidetaka , Kobayashi Hisae , Iwase Akira , Sato Ken
Published: July 2021

Fertilization triggers significant cellular remodeling through the oocyte-to-embryo transition. In this transition, the ubiquitin-proteasome system and autophagy are essential for the degradation of maternal components; however, the significance of degradation of cell surface components remains unknown. In this study, we show that multiple maternal plasma membrane proteins, such as the glycine transporter GlyT1a, are selectively internalized from the plasma membrane to endosomes in mouse embryos by the late two-cell stage and then transported to lysosomes for degradation at the later stages. During this process, large amounts of ubiquitylated proteins accumulated on endosomes. Furthermore, the degradation of GlyT1a with mutations in potential ubiquitylation sites was delayed, suggesting that ubiquitylation may be involved in GlyT1a degradation. The clathrin inhibitor blocked GlyT1a internalization. Strikingly, the protein kinase C (PKC) activator triggered the heterochronic internalization of GlyT1a; the PKC inhibitor markedly blocked GlyT1a endocytosis. Lastly, clathrin inhibition completely blocked embryogenesis at the two-cell stage and inhibited cell division after the four-cell stage. These findings demonstrate that PKC-dependent clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins during oocyte-to-embryo transition and early embryogenesis.
Radical Hemiscrotectomy and En Bloc Orchidectomy: Surgical Technique and Perioperative and Oncologic Outcomes of a Supra-Regional UK Referral Centre
Authors: Fankhauser Christian Daniel , Issa Allaudin , Lee Esther W. C. , Oing Christoph , Oliveira Pedro , Parnham Arie , Oates Jeremy , Sangar Vijay , Gulamhusein Aziz , Clarke Noel
Published: July 2021

Background and Purpose

Hemiscrotectomy with en bloc orchidectomy represents a radical primary, completion, or salvage option in men with inguinoscrotal cancers. We describe our surgical technique and peri-operative and oncological outcomes.

Patients and Methods

Retrospective cohort study of 16 men treated at a supra-regional referral centre with open radical hemiscrotectomy with or without en bloc orchidectomy between 2010 and 2020. Peri-operative and survival outcomes were analysed.

Results

Radical hemiscrotectomy with or without en bloc orchidectomy was performed on 16 patients comprising 7 well-differentiated liposarcomas, 4 dedifferentiated liposarcomas, 2 leiomyosarcomas, 1 mesothelioma, 1 rhabdomyosarcoma and 1 mammary type myofibroblastoma. Primary hemiscrotectomy was performed in four, completion hemiscrotectomy in nine and salvage hemiscrotectomy in three. The median hospital stay was 2 days [interquartile range (IQR) 2–4]. Four patients (25%) had post-operative complications including wound infection or haematoma. During a median follow-up of 18 months (IQR 2–66), one patient (6%) died following a recurrence in the pelvis and retroperitoneum.

Discussion

and Conclusions

If careful dissection is performed, radical hemiscrotectomy and en bloc orchidectomy is a radical but safe procedure with a short hospital stay. Haematoma and infection represent the main complications, and within limited follow-up most men showed no recurrence.
Community-level influences on women’s experience of intimate partner violence and modern contraceptive use in Nigeria: a multilevel analysis of nationally representative survey
Authors: Adedini Sunday A. , Adewole Ololade Grace , Oyinlola Funmilola F. , Fayehun Olufunke
Published: July 2021

Background: Modern contraceptives (MC) are important strategies for reducing unwanted pregnancies, unsafe abortion and maternal mortality, but MC remains low at 18% in Nigeria. Similarly, while there is increasing prevalence of intimate partner violence (IPV) in Nigeria, its effects on contraceptive use remain unclear. This study examined the influence of IPV on MC use, while adjusting for individual- and community-level confounders.

Methods: The study utilized 2018 Nigeria Demographic and Health Survey data. We performed multilevel binary logistic regression analysis on 24,973 married women aged 15-49, who were sexually active and were not pregnant at the time of the survey.

Results: Findings show that use of MC was higher among married women who reported experience of IPV than those without IPV exposure. After adjusting for individual-level and contextual factors, the odds of using MC was significantly higher among women who experienced any form of IPV (OR: 1.61, 95% CI: 1.17-2.21, p<0.005) compared to those who reported no IPV experience. Around one-quarter of the total variance in contraceptive use with respect to the different types of IPV could be explained at the community level.

Conclusion: The study provides empirical evidence that there is signiﬁcant community effect on IPV exposure and women’s contraceptive uptake. Attention must therefore be given to the context-specific social and gender norms that affect women’s sexual and reproductive health in Nigeria.
Nationalising the Harappan Past
Authors: Kumar Ashish
Published: July 2021

The Harappan civilisation that was discovered in the early 1920s became a matter of intense debate in the decades following the partition of India in 1947. As the boundaries of the newly created nation-states, Pakistan and India were drawn, almost entire excavated area associated with the Harappan civilisation went to Pakistan. And it inaugurated an era of academic politics in which Pakistani scholars and politicians claimed a five thousand years old antiquity for their nation-state based on the Harappan civilisation. On the other hand, the Indian archaeologists began searching for the Harappan sites in the valley of the Ghaggar (identified with Rigvedic Sarasvati River) – now dry, to justify India’s linkages with the same civilisation. In this academic politics, one British archaeologist, R. E. Mortimer Wheeler (the Director General of the Archaeological Survey of India; from 1944 to 1948, and Archaeological advisor to Pakistan ministry; from 1948 to 1950) played a central role. Both, colleagues and several erstwhile students of this Englishman in India and Pakistan, this paper argues that participated in this academic politics. As they formulated a new national historical framework, the Harappan civilisation was transformed into a first civilisational landmark in the history of their respective countries.
The Travel and Tourism Industry
Authors: George Alisha , Sunny Sonu , Kapoor Anusha , Kaur Saggu Japjot , Puri Paridhi , Munjal Sanaa , Bamba Visaaya
Published: July 2021

First to be hit by the pandemic and last to recover, the travel and tourism industry is considered to be one of the most severely affected sectors. The paper tries to highlight the vulnerabilities of GDP, employment and related activities of the tourism sector by looking at it through a macro perspective using data from the World Bank, International Labour Organization, the United Nations World Trade Organization and, the World Travel and Tourism Council, in addition, substantiating the results through micro evidences in the form of case studies. The paper, using quantitative and qualitative methods, shows that GDP, employment and related activities are susceptible to the pandemic- COVID-19 and suggests how to pandemic-proof the sector that not only contributes significantly to GDP but weaves the thread of interconnectedness across the world.
Analysing the Differential Performances of Indian States in the Tourism Sector
Authors: Jacob Megha , Agarwal Archita , Gupta Gunjan , Raju Kavya Maria , Khurana Rabani
Published: July 2021

Tourism is an ever evolving and a dynamic industry which can play a crucial role in increasing income and in providing employment opportunities in an economy. India especially with its rich heritage, culture and geographical landscapes has always had immense potential to become a leading tourist destination. Presently the major types of tourism prevalent in India are Medical Tourism, Rural/ Natural Tourism, Religious Tourism and Historical& Educational Tourism. In 2018-19, the tourism sector contributed around 5% to India’s GDP. However with the health shock of Covid-19, the tourism sector has taken a major hit since early 2020, with several people losing their jobs in the tourism and hospitality sector when different states imposed lockdowns and took various measures to curb the pandemic. As restrictions in each state eased during the first wave of the pandemic, different states in India adopted various policies to revive the tourism industry. But to understand the effectiveness of these policies in each state/ UT, one needs to investigate the baseline at which the Tourism industry was before the pandemic hit the country. This paper attempts to look at the differential performances of states and UTs of India in tourism by categorizing them into various types of tourism between 1947 until March 2020.This paper aims to act as a base for further analysing the impact of this pandemic on Tourism across states in India.
Post-Pandemic Travel
Authors: N Sneha
Published: July 2021

The Indian tourism industry has reached a great scale over the years. With the over-increasing internet penetration, more travellers are booking online travel in India. However, the world and in particular the tourism industry has seen an unprecedented shutdown due to Covid-19 affecting 2020 due to the absence of a universal vaccination at the moment. It is important to understand the current scenario of Indian travel patterns prior to the impact of Corona Virus and the factors which will be influencing the decision-making process of Indian Travellers in the future. Hence, this paper attempts to study and decode the decision-making process of Indian Travellers through extensive review of contemporary academic literature on post-pandemic tourism emerging with COVID-19 crisis. This study area is important because it addresses a pressing problem of comprehending the post pandemic travel and the research outcome suggests practical solutions to overcome the critical barriers arising out of Covid-19 for Indian Travellers and learn to practice a new way of travelling in the future.
Adversarial Risk Analysis for Auctions Using Mirror Equilibrium and Bayes Nash Equilibrium
Authors: Ejaz Muhammad , Joe Stephen , Joshi Chaitanya
Published: July 2021

In this paper, we use the adversarial risk analysis (ARA) methodology to model first-price sealed-bid auctions under quite realistic assumptions. We extend prior work to find ARA solutions for mirror equilibrium and Bayes Nash equilibrium solution concepts, not only for risk-neutral but also for risk-averse and risk-seeking bidders. We also consider bidders having different wealth and assume that the auctioned item has a reserve price.