bluuebunny/crossref_metadata_2025 huggingface dataset:
Contralateral radiculopathy after unilateral transforaminal lumbar interbody fusion: causes and prevention
Authors: Chen Yun-lin , Hu Xu-dong , Wang Yang , Jiang Wei-yu , Ma Wei-hu
Published: August 2021

Background

Unilateral transforminal lumbar interbody fusion (TLIF) with a single cage can provide circumferential fusion and biomechanical stability. However, the causes and prevention of contralateral radiculopathy following unilateral TLIF remain unclear.

Methods

In total, 190 patients who underwent unilateral TLIF from January 2017 to January 2019 were retrospectively reviewed. Radiological parameters including lumbar lordosis, segmental angle, anterior disc height, posterior disc height (PDH), foraminal height (FH), foraminal width, and foraminal area (FA) were measured preoperatively and postoperatively. Preoperative and postoperative visual analog scale scores were also recorded.

Results

The incidence of contralateral radiculopathy after unilateral TLIF was 5.3% (10/190). The most common cause was contralateral foraminal stenosis. Unilateral TLIF could increase the lumbar lordosis, segmental angle, and anterior disc height but decrease the PDH, FA, and FH in patients with symptomatic contralateral radiculopathy. The intervertebral cage should be placed to cover the epiphyseal ring and cortical compact bone of the midline, and the disc height can be increased to enlarge the contralateral foramen.

Conclusion

The most common cause of contralateral radiculopathy is contralateral foraminal stenosis. Careful preoperative planning is necessary to achieve satisfactory outcomes. Improper unilateral TLIF will decrease the PDH, FA, and FH, resulting in contralateral radiculopathy.
Notch-based speed trajectory optimisation for high-speed railway automatic train operation
Authors: Feng Minling , Wu Chaoxian , Lu Shaofeng , Wang Yihui
Published: August 2021

Automatic train operation (ATO) systems are fast becoming one of the key components of the intelligent high-speed railway (HSR). Designing an effective optimal speed trajectory for ATO is critical to guide the high-speed train (HST) to operate with high service quality in a more energy-efficient way. In many advanced HSR systems, the traction/braking systems would provide multiple notches to satisfy the traction/braking demands. This paper modelled the applied force as a controlled variable based on the selection of notch to realise a notch-based train speed trajectory optimisation model to be solved by mixed integer linear programming (MILP). A notch selection model with flexible vertical relaxation was proposed to allow the traction/braking efforts to change dynamically along with the selected notch by introducing a series of binary variables. Two case studies were proposed in this paper where Case study 1 was conducted to investigate the impact of the dynamic notch selection on train operations, and the optimal result indicates that the applied force can be flexibly adjusted corresponding to different notches following a similar operation sequence determined by optimal train control theory. Moreover, in addition to the maximum traction/braking notches and coasting, medium notches with appropriate vertical relaxation would be applied in accordance with the specific traction/braking demands to make the model feasible. In Case study 2, a comprehensive numerical example with the parameters of CRH380AL HST demonstrates the robustness of the model to deal with the varying speed limit and gradient in a real-world scenario. The notch-based model is able to obtain a more realistic optimal strategy containing dynamic notch selection and speed trajectory with an increase (1.622%) in energy consumption by comparing the results of the proposed model and the non-notch model.
Strength Versus Sensitivity: The Impact of Attorney Gender on Juror Perceptions and Trial Outcomes in a Rape Case
Authors: Levi Mary M. , Lynch Kellie R. , Golding Jonathan M.
Published: August 2021

We examined the impact of attorney gender on perceptions of a criminal rape trial. Community members ( N = 208) read a trial summary describing a rape scenario in which the gender of the prosecuting and defense attorney were manipulated. The results revealed indirect effects of prosecuting and defense attorney gender on verdict through perceptions of characteristics related to attorney competency. Qualitative analyses further showed that the terms “strength” and “powerful” were central to juror perceptions of male attorneys, whereas the terms “sensitive” and “sympathy” were central when the attorneys were female.
Impact of Home Care Services on Patient and Economic Outcomes: A Targeted Review
Authors: Lizano-Díez Irene , Amaral-Rohter Sonia , Pérez-Carbonell Lucía , Aceituno Susana
Published: August 2021

Patient Support Programs (PSPs) reinforce patients’ care provided by health care professionals with the aim to improve adherence and patient empowerment. PSPs may include interventions such as home-based care, individualized medication counseling, support, training, and home delivery of medicines and/or devices. This study described these services and its impact on patient-reported outcomes and health care savings. We conducted an integrative literature review which was limited to publications from the last 10 years (2009-2019) and focused on diseases that require special support and/or parenteral administration. From 7040 total citations, we identified 64 home-based care services performed worldwide. Among the home-based care services, most were provided by nurses (n = 47/64; 73.4%) and addressed to cancer patients (n = 22/64; 34.4%); 23 out of 64 services (35.9%) incorporated telepharmacy. In general, home-based services and PSPs showed a positive impact on patients’ adherence to medication, patient satisfaction, and health-related quality of life. In addition, 14 (21.9%) services reported economic results, most of which showed that home therapy led to substantial cost savings.
PKR deficiency alleviates pulmonary hypertension via inducing inflammasome adaptor ASC inactivation
Authors: Li Yapei , Li Ying , Li Lijun , Yin Minghui , Wang Jiangang , Li Xiaohui
Published: August 2021

Pulmonary hypertension is a progressive fatal disease that currently has no specific therapeutic approaches. In this study, dsRNA‐dependent protein kinase (PKR) was considered a candidate molecule in pulmonary hypertension. We demonstrated that PKR is activated in the endothelium of experimental pulmonary hypertension models. Deletion of PKR or treatment with the PKR activation inhibitor C16 inhibited the development of pulmonary hypertension. To explore the mechanism of PKR in pulmonary hypertension, we detected its downstream signaling and found that PKR knockout represses apoptosis‐associated speck‐like protein containing CARD (ASC) activation to inhibit high mobility group box 1 (HMGB1) and interleukin‐1 beta release. To further explore whether ASC mediates the pro‐pulmonary hypertension role of PKR, we used ASC deletion mice and found that ASC deletion inhibits the development of pulmonary hypertension and the release of HMGB1 and interleukin‐1 beta. Furthermore, we co‐cultured pulmonary arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells (PASMCs) and found that endothelial PKR promotes PASMCs proliferation through the release of HMGB1 and interleukin‐1 beta. In conclusion, these data indicate that endothelial PKR promotes the excessive proliferation of PASMCs by inducing ASC activation to release HMGB1 and interleukin‐1 beta, which lead to the development of pulmonary hypertension. Our study will provide a novel insight that PKR is a potential target in the future treatment of pulmonary hypertension.
Effect of maternal near miss on neonatal mortality in selected hospitals: Prospective cohort study, Southeast Ethiopia
Authors: Aliyi Ahmednur Adem , Deyessa Negussie , Dilnessie Mengistu Yilma
Published: August 2021

Objective:

The objective of this study was to assess effect of maternal near miss on neonatal mortality.

Methods:

Prospective cohort study was conducted on 384 pregnant women who came for delivery to purposely selected hospitals. The cohort was made up of 128 exposed (near miss) mothers and 256 non-exposed (non-near-miss) mothers. Women who came for delivery were only included. Those who came for services other than delivery such as abortion care, women who developed life-threatening condition not related to delivery, and those who come from no phone network area were excluded. A purposive sampling technique was used by including all mothers with near miss consecutively until the required sample size was obtained. Two non-near-miss mothers were selected using lottery for every near-miss mother. Survival analysis was done for both groups using Cox regression to look for effect of maternal near miss on neonatal mortality. Verbal informed consent from study participants was obtained.

Results:

A total of 354 (118 with near miss and 236 without near miss) women completed the follow-up time, yielding response rate of 92.2%. Of all, 55 (15.5%) of them have previous history of abortion, 44 (12.4%) were admitted to the intensive care unit during delivery, and 22 (6.2%) have history of past delivery of still birth. Severe preeclampsia with intensive care unit admission and severe anemia with transfusion of greater than 2 units of blood were common complications leading to maternal near miss. There were 17 (48 per 1000 live birth) neonatal death at the end of the study, of which 15 occurred among mothers with near miss. Monthly income (adjusted hazard ratio = 998, 95% confidence interval = 0.996–0.999), fetal presentation (adjusted hazard ratio = 6.48, 95% confidence interval = 1.84–22.73), APGAR score (adjusted hazard ratio = 0.746, 95% confidence interval = 0.620–0.898), and being near miss mother (adjusted hazard ratio = 8.40, 95% confidence interval = 1.638–43.118) were significantly affecting neonatal mortality.

Conclusion:

Maternal near miss and other fetal and general maternal characteristics have effect on occurrence of neonatal mortality. Therefore, due attention should be given to these factors for improvement of neonatal survival.
Energy-Optimal Braking Control Using a Double-Layer Scheme for Trajectory Planning and Tracking of Connected Electric Vehicles
Authors: Dong Haoxuan , Zhuang Weichao , Yin Guodong , Xu Liwei , Wang Yan , Wang Fa’an , Lu Yanbo
Published: August 2021

Most researches focus on the regenerative braking system design in vehicle components control and braking torque distribution, few combine the connected vehicle technologies into braking velocity planning. If the braking intention is accessed by the vehicle-to-everything communication, the electric vehicles (EVs) could plan the braking velocity for recovering more vehicle kinetic energy. Therefore, this paper presents an energy-optimal braking strategy (EOBS) to improve the energy efficiency of EVs with the consideration of shared braking intention. First, a double-layer control scheme is formulated. In the upper-layer, an energy-optimal braking problem with accessed braking intention is formulated and solved by the distance-based dynamic programming algorithm, which could derive the energy-optimal braking trajectory. In the lower-layer, the nonlinear time-varying vehicle longitudinal dynamics is transformed to the linear time-varying system, then an efficient model predictive controller is designed and solved by quadratic programming algorithm to track the original energy-optimal braking trajectory while ensuring braking comfort and safety. Several simulations are conducted by jointing MATLAB and CarSim, the results demonstrated the proposed EOBS achieves prominent regeneration energy improvement than the regular constant deceleration braking strategy. Finally, the energy-optimal braking mechanism of EVs is investigated based on the analysis of braking deceleration, battery charging power, and motor efficiency, which could be a guide to real-time control.
MoS2 with Controlled Thickness for Electrocatalytic Hydrogen Evolution
Authors: Xu Xiaoxuan , Liu Lei
Published: August 2021

Molybdenum disulfide (MoS2) has moderate hydrogen adsorption free energy, making it an excellent alternative to replace noble metals as hydrogen evolution reaction (HER) catalysts. The thickness of MoS2 can affect its energy band structure and interface engineering, which are the avenue way to adjust HER performance. In this work, MoS2 films with different thicknesses were directly grown on the glassy carbon (GC) substrate by atomic layer deposition (ALD). The thickness of the MoS2 films can be precisely controlled by regulating the number of ALD cycles. The prepared MoS2/GC was directly used as the HER catalyst without a binder. The experimental results show that MoS2 with 200-ALD cycles (the thickness of 14.9 nm) has the best HER performance. Excessive thickness of MoS2 films not only lead to the aggregation of dense MoS2 nanosheets, resulting in reduction of active sites, but also lead to the increase of electrical resistance, reducing the electron transfer rate. MoS2 grown layer by layer on the substrate by ALD technology also significantly improves the bonding force between MoS2 and the substrate, showing excellent HER stability.
Understanding the determinants of COVID-19 vaccination intention and willingness to pay: findings from a population-based survey in Bangladesh
Authors: Banik Rajon , Islam Md. Saiful , Pranta Mamun Ur Rashid , Rahman Quazi Maksudur , Rahman Mahmudur , Pardhan Shahina , Driscoll Robin , Hossain Sahadat , Sikder Md. Tajuddin
Published: August 2021

Background

Several coronavirus disease (COVID-19) vaccines have already been authorized and distributed in different countries all over the world, including Bangladesh. Understanding public acceptance of such a novel vaccine is vital, but little is known about the topic.

Objectives

This study aimed to investigate the determinants of intention to receive a COVID-19 vaccine and willingness to pay (WTP) among people in Bangladesh.

Methods

An anonymous and online-based survey of Bangladeshi people (mean age = 29.96 ± 9.15 years; age range = 18–60 years) was conducted using a self-reported questionnaire consisting of socio-demographics, COVID-19 experience, and vaccination-related information as well as the health belief model (HBM). Multivariable logistic regression was performed to determine the factors influencing COVID-19 vaccination intent and WTP.

Results

Of the 894 participants, 38.5% reported a definite intention to receive a COVID-19 vaccine, whereas 27% had a probable intention, and among this intent group, 42.8% wanted to get vaccinated as soon as possible. Older age, feeling optimistic about the effectiveness of COVID-19 vaccination, believing that vaccination decreases worries and risk of COVID-19 infection, and being less concerned about side effects and safety of COVID-19 vaccination under the HBM construct were found to be significant factors in COVID-19 vaccination intention. Most of the participants (72.9%) were willing to pay for a COVID-19 vaccine, with a median (interquartile range [IQR]) amount of BDT 400/US$ 4.72 (IQR; BDT 200–600/US$ 2.36–7.07) per dose. Factors associated with higher WTP were younger age, being male, having higher education, residing in an urban area, having good self-rated health status, positivity towards COVID-19 vaccination's effectiveness, and being worried about the likelihood of getting infected with COVID-19. Participants who were COVID-19 vaccination intent preferred an imported vaccine over a domestically-made vaccine (22.9% vs. 14.8%), while 28.2% preferred a routine immunization schedule.

Conclusion

The findings indicate a considerable proportion of Bangladeshi people intended to get vaccinated and had WTP for the COVID-19 vaccine. However, urgent education and awareness programs are warranted to alleviate public skepticism regarding the COVID-19 vaccination.
Infectious keratitis after corneal crosslinking for keratoconus caused by levofloxacin-resistant microorganisms
Authors: Kato Naoko , Ide Takeshi , Kobashi Hidenaga , Toda Ikuko
Published: August 2021

Introduction

We present seven cases of infectious keratitis after corneal crosslinking (CXL) to attenuate keratoconus progression.

Methods

Of 524 consecutive patients who underwent CXL, 7 cases (4 males and 3 females; 21.5 ± 7.1 years) developed postoperative infectious keratitis were retrospectively reviewed. CXL was performed using the Dresden protocol or an accelerated protocol involving epithelial removal.

Results

All cases appeared normal on the day after surgery, but subsequently developed eye pain, blurred vision, corneal infiltration, inflammation of the anterior chamber, and ciliary injection on day 2 or 3. Methicillin-resistant Staphylococcus aureus was cultured from two eyes, methicillin-sensitive Staphylococcus aureus from two eyes, and Streptococcus pneumoniae from one eye. All detected bacteria were resistant to levofloxacin (LVFX). Five of the seven cases, especially four of the five severe cases with hypopyon, had a history of atopic dermatitis. All cases were observed after 2015.

Conclusions

Infectious keratitis after CXL caused by microbes resistant to LVFX is increasing. In addition to careful postoperative observation of the cornea, preoperative evaluation of bacteria within the conjunctival sac evident on nasal swab cultures may be useful to identify potentially problematic microbes and inform the selection of appropriate antibiotics.
The impact of implementing a psychiatric emergency hotline on the reduction of acute hospitalizations in a Swiss tertiary hospital
Authors: Restellini Aurélio , Kherad Omar , Kaiser Stefan
Published: August 2021

Background

Inpatient treatment is not the most beneficial treatment setting for many patients with psychiatric disorders and overcrowding is a recurrent problem for psychiatric hospitals. Therefore, it is important to develop strategies to limit avoidable inpatient treatment. This study sought to evaluate the impact of an emergency hotline that was developed to better manage psychiatric patients, particularly for identifying those requiring a hospital admission.

Methods

This pre-post intervention quality improvement study compared changes in the management of psychiatric patients’ admission before and after the introduction of an emergency hotline where a specialist in psychiatry examines all inpatient referral from private practitioners.

Main outcomes were the change in proportion of hospital admissions after referral from a private practitioner before and within 3 months after the intervention. Secondary outcomes were the average length of hospital stay, proportion of non-voluntary admission, the time required for triage and the impact of the intervention on treatments’ costs. Fisher’s Exact test was used to test the primary hypothesis of difference in the proportion of hospitalized patients before and after introduction of the emergency hotline. Secondary outcomes were tested with Student’s t-test for continuous variables and Fishers’s Exact test for proportions.

Results

Among 45 admission requests from private practitioners during the 3 months after introduction of the new emergency hotline, 25 (55.6%) were accepted as inpatient treatment, while 20 (44%) were redirected to more appropriate outpatient treatments. There was a highly significant difference from the baseline period during which all 34 requests were accepted (44% vs 100%, p < 0.001). In addition, for the patients hospitalized after the introduction of the emergency hotline there was a trend-level reduction of the average length of stay (9.32 days vs 17.35 days).

Conclusion

Implementation of an emergency hotline manage by a specialist in psychiatry for admissions to acute psychiatric wards is feasible and simple to use. Importantly, it allows to significantly decrease the proportion of hospitalizations. Additional studies are needed to assess the generalizability of these exploratory results to other health care settings.
Serum level of high sensitive C-reactive protein and IL − 6 markers in patients with treatment-resistant schizophrenia in Ethiopia: a comparative study
Authors: Challa Feyissa , Seifu Daniel , Sileshi Meron , Getahun Tigist , Geto Zeleke , Kassa Desta , Alemayehu Melkam , Mesfin Miraf , Fekadu Abebaw , Woldeamanuel Yimtubezinash
Published: August 2021

Background

Accumulating evidence indicates that schizophrenia is accompanied by significant activation of the immune system; however, there is limited data from low and middle-income countries (LMIC). Inflammatory markers may be more relevant in LMIC settings where infectious conditions are more prevalent and may thus play some role in the causation and maintenance of schizophrenia. The aim of this study was to assess the level of inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with schizophrenia.

Materials and methods

The study population consisted of a total of 132 study participants; 82 participants with schizophrenia and 50 controls. hsCRP and IL-6 were measured using Cobas Integra 400 Plus and Cobas e 411 analysers respectively.

Results

The levels of hsCRP and IL-6 were significantly increased among participants with schizophrenia compared to controls: hsCRP mean value 2.87 ± 5.6 vs 0.67 ± 0.6 mg/L; IL-6 mean value 6.63 ± 5.6 vs 3.37 ± 4.0 pg/ml. Controlling for potential confounders (age, sex and body mass index), having a diagnosis of schizophrenia remained significantly associated with increased hsCRP and IL-6.

Conclusion

The results confirm that inflammatory processes may have a role in the pathophysiology of schizophrenia regardless of setting. Despite failure of some interventions with anti-inflammatory properties, interventions to reduce inflammation are still worth pursuing.
A mixed-methods investigation to understand and improve the scaled-up infection prevention and control in primary care health facilities during the Ebola virus disease epidemic in Sierra Leone
Authors: Ho Lara Shiu-yi , Ratnayake Ruwan , Ansumana Rashid , Brown Hannah
Published: August 2021

Background

The 2014–2015 Ebola epidemic in West Africa became a humanitarian crisis that exposed significant gaps in infection prevention and control (IPC) capacity in primary care facilities in Sierra Leone. Operational partners recognized the national gap and rapidly scaled-up an IPC training and infrastructure package. This prompted us to carry out a mixed-methods research study which aimed to evaluate adherence to IPC practices and understand how to improve IPC at the primary care level, where most cases of Ebola were initially presenting. The study was carried out during the national peak of the epidemic.

Discussion

We successfully carried out a rapid response research study that produced several expected and unexpected findings that were used to guide IPC measures during the epidemic. Although many research challenges were similar to those found when conducting research in low-resource settings, the presence of Ebola added risks to safety and security of data collectors, as well as a need to balance research activities with the imperative of response to a humanitarian crisis. A participatory approach that attempted to unify levels of the response from community upwards helped overcome the risk of lack of trust in an environment where Ebola had damaged relations between communities and the health system.

Conclusion

In the context of a national epidemic, research needs to be focused, appropriately resourced, and responsive to needs. The partnership between local academics and a humanitarian organization helped facilitate access to study sites and approvals that allowed the research to be carried out quickly and safely, and for findings to be shared in response forums with the best chance of being taken up in real-time.
“You get three different hats on and try to figure it out:” home based care provision during a disaster
Authors: Bell Sue Anne , Dickey Sarah , Rosemberg Marie-Anne
Published: August 2021

Background

Home based care is a vital, and growing, part of the health care system that allows individuals to remain in their homes while still receiving health care. During a disaster, when normal health care systems are disrupted, home based care remains a vital source of support for older adults. The purpose of this paper is to qualitatively understand the barriers and facilitators of both patients and providers that influence the provision of home based care activities in two hurricane affected communities.

Methods

Using qualitative inquiry informed by the social ecological model, five focus groups were conducted with home based care providers (n = 25) in two settings affected by Hurricane Irma and Hurricane Harvey. An open-source database of home health agencies participating in Centers for Medicare and Medicaid Services programs was used to identify participants. Data were manually coded and larger themes were generated from recurring ideas and concepts using an abductive analysis approach.

Results

Twenty five participants were included in one of five focus groups. Of the 22 who responded to the demographic survey, 65 % were registered nurses, 20 % were Licensed Vocational Nurses (LVN), and 15 % were other types of health care providers. 12 % of the sample was male and 88 % was female. Five themes were identified in the analysis:barriers to implementing preparedness plans,adaptability of home based care providers, disasters exacerbate inequalities,perceived unreliability of government and corporations, andthe balance between caring for self and family and caring for patients.

Conclusions

This study provides qualitative evidence on the factors that influence home based care provision in disaster-affected communities, including the barriers and facilitators faced by both patients and providers in preparing for, responding to and recovering from a disaster. While home based care providers faced multiple challenges to providing care during and after a disaster, the importance of community supports and holistic models of care in the immediate period after the disaster were emphasized. We recommend greater inclusion of home health agencies in the community planning process. This study informs the growing body of evidence on the value of home based care in promoting safety and well-being for older adults during a disaster.
Administration of indwelling urinary catheters in four Australian Hospitals: cost-effectiveness analysis of a multifaceted nurse-led intervention
Authors: Ling Rod , Giles Michelle , Searles Andrew
Published: August 2021

Background

Urinary catheters are useful among hospital patients for allowing urinary flows and preparing patients for surgery. However, urinary infections associated with catheters cause significant patient discomfort and burden hospital resources. A nurse led intervention aiming to reduce inpatient catheterisation rates was recently trialled among adult overnight patients in four New South Wales hospitals. It included: ‘train-the trainer’ workshops, site champions, compliance audits and promotional materials. This study is the ‘in-trial’ cost-effectiveness analysis, conducted from the perspective of the New South Wales Ministry of Health.

Methods

The primary outcome variable was catheterisation rates. Catheterisation and procedure/treatment data were collected in three point prevalence patient surveys: pre-intervention (n = 1630), 4-months (n = 1677), and 9-months post-intervention (n = 1551). Intervention costs were based on trial records while labour costs were gathered from wage awards. Incremental cost effectiveness ratios were calculated for 4- and 9-months post-intervention and tested with non-parametric bootstrapping. Sensitivity scenarios recalculated results after adjusting costs and parameters.

Results

The trial found reductions in catheterisations across the four hospitals between preintervention (12.0 % (10.4 − 13.5 %), n = 195) and the 4- (9.9 % (8.5 − 11.3 %), n = 166 ) and 9- months (10.2 % (8.7 − 11.7 %) n = 158) post-intervention points. The trend was statistically non-significant (p = 0.1). Only one diagnosed CAUTI case was observed across the surveys. However, statistically and clinically significant decreases in catheterisation rates occurred for medical and critical care wards, and among female patients and short-term catheterisations. Incremental cost effectiveness ratios at 4-months and 9-months post-intervention were $188 and $264. Bootstrapping found reductions in catheterisations at positive costs over at least 72 % of iterations. Sensitivity scenarios showed that cost effectiveness was most responsive to changes in catheterisation rates.

Conclusions

Analysis showed that the association between the intervention and changes in catheterisation rates was not statistically significant. However, the intervention resulted in statistically significant reductions for subgroups including among short-term catheterisations and female patients. Cost-effectiveness analysis showed that reductions in catheterisations were most likely achieved at positive cost.

Trial Registration

Registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000090314). First hospital enrolment, 15/11/2016; last hospital enrolment, 8/12/2016.
Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae
Authors: Lindsey Charles Ross , Rosenzweig Frank , Herron Matthew D.
Published: August 2021

Background

The volvocine algae, which include the single-celled species Chlamydomonas reinhardtii and the colonial species Volvox carteri, serve as a model in which to study the evolution of multicellularity and cellular differentiation. Studies reconstructing the history of this group have by and large relied on datasets of one to a few genes for phylogenetic inference and ancestral character state reconstruction. As a result, volvocine phylogenies lack concordance depending on the number and/or type of genes (i.e., chloroplast vs nuclear) chosen for phylogenetic inference. While multiple studies suggest that multicellularity evolved only once in the volvocine algae, that each of its three colonial families is monophyletic, and that there have been at least three independent origins of cellular differentiation in the group, other studies call into question one or more of these conclusions. An accurate assessment of the evolutionary history of the volvocine algae requires inference of a more robust phylogeny.

Results

We performed RNA sequencing (RNA-seq) on 55 strains representing 47 volvocine algal species and obtained similar data from curated databases on 13 additional strains. We then compiled a dataset consisting of transcripts for 40 single-copy, protein-coding, nuclear genes and subjected the predicted amino acid sequences of these genes to maximum likelihood, Bayesian inference, and coalescent-based analyses. These analyses show that multicellularity independently evolved at least twice in the volvocine algae and that the colonial family Goniaceae is not monophyletic. Our data further indicate that cellular differentiation arose independently at least four, and possibly as many as six times, within the volvocine algae.

Conclusions

Altogether, our results demonstrate that multicellularity and cellular differentiation are evolutionarily labile in the volvocine algae, affirming the importance of this group as a model system for the study of major transitions in the history of life.
Detecting copy number variation in next generation sequencing data from diagnostic gene panels
Authors: Singh Ashish Kumar , Olsen Maren Fridtjofsen , Lavik Liss Anne Solberg , Vold Trine , Drabløs Finn , Sjursen Wenche
Published: August 2021

Background

Detection of copy number variation (CNV) in genes associated with disease is important in genetic diagnostics, and next generation sequencing (NGS) technology provides data that can be used for CNV detection. However, CNV detection based on NGS data is in general not often used in diagnostic labs as the data analysis is challenging, especially with data from targeted gene panels. Wet lab methods like MLPA (MRC Holland) are widely used, but are expensive, time consuming and have gene-specific limitations. Our aim has been to develop a bioinformatic tool for CNV detection from NGS data in medical genetic diagnostic samples.

Results

Our computational pipeline for detection of CNVs in NGS data from targeted gene panels utilizes coverage depth of the captured regions and calculates a copy number ratio score for each region. This is computed by comparing the mean coverage of the sample with the mean coverage of the same region in other samples, defined as a pool. The pipeline selects pools for comparison dynamically from previously sequenced samples, using the pool with an average coverage depth that is nearest to the one of the samples. A sliding window-based approach is used to analyze each region, where length of sliding window and sliding distance can be chosen dynamically to increase or decrease the resolution. This helps in detecting CNVs in small or partial exons. With this pipeline we have correctly identified the CNVs in 36 positive control samples, with sensitivity of 100% and specificity of 91%. We have detected whole gene level deletion/duplication, single/multi exonic level deletion/duplication, partial exonic deletion and mosaic deletion. Since its implementation in mid-2018 it has proven its diagnostic value with more than 45 CNV findings in routine tests.

Conclusions

With this pipeline as part of our diagnostic practices it is now possible to detect partial, single or multi-exonic, and intragenic CNVs in all genes in our target panel. This has helped our diagnostic lab to expand the portfolio of genes where we offer CNV detection, which previously was limited by the availability of MLPA kits.
Free fatty acids and triglyceride change in the gallbladder bile of gallstone patients with pancreaticobiliary reflux
Authors: Xiang Yukai , Kong Xiangyu , Zhang Cheng , He Chuanqi , Cai Jingli , Lu Ruiqi , Zhang Bosen , Lu Liu , Yang Yulong
Published: August 2021

Background

Pancreaticobiliary reflux (PBR) causes chronic inflammation of the gallbladder mucosa and changes in the bile components, which are known to promote gallstone formation. This study aimed to investigate the bile biochemistry changes in gallstone patients with PBR and provide new clues for research on the involvement of PBR in gallstone formation.

Methods

Patients undergoing surgery for gallstones between December 2020 and May 2021 were eligible for inclusion. The bile biochemistry (including amylase, lipase, triglyceride, cholesterol, free fatty acids [FFAs], alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and γ-glutamyl transferase [γ-GT]) of the included gallstone patients was analysed to determine correlations with PBR.

Results

In this study, 144 gallstone patients who underwent surgery were enrolled. Overall, 15.97 % of the patients had an increased bile amylase level, which was associated with older age and significantly higher bile levels of ALP, lipase, triglyceride, and FFAs. Positive correlations were observed between amylase and lipase, triglyceride, FFAs levels in the gallbladder bile. However, the bile levels of triglyceride, FFAs, and lipase were positively correlated with each other only in the PBR group and showed no significant correlation in the control (N) group. In addition, elevated bile FFAs levels were found to be an independent risk factor for gallbladder wall thickening.

Conclusions

In conclusion, PBR-induced increase in FFAs and triglyceride in the gallbladder bile is a cause of gallstone formation, and an increase in bile ALP suggests the presence of cholestasis in PBR.
How a sample of English stop smoking services and vape shops adapted during the early COVID-19 pandemic: a mixed-methods cross-sectional survey
Authors: Cox Sharon , Ward Emma , Ross Louise , Notley Caitlin
Published: August 2021

Background

The COVID-19 pandemic in England led to major changes in the delivery of support via stop smoking services (SSS) and to the widespread temporary closure of bricks and mortar e-cigarette retailers (vape shops herein). The impact of disruptions across the smoking cessation support landscape has not been fully documented. The purpose of this study was to capture how SSS and vape shops in England were affected and adapted their ‘business as usual’ during the early months of the COVID-19 pandemic.

Method

An online cross-sectional survey was conducted between March and July 2020. Surveys were disseminated through online networks, professional forums and contacts. Open-ended qualitative responses were coded using thematic analysis.

Results

Responses from 46 SSS and 59 vape shops were included. SSS were able to adapt during this period, e.g. offering a remote service. A high percentage (74.6%) of vape shops had to close and were unable to make changes; 71.2% reported business declining. For both vape shops and SSS qualitative data revealed practical challenges to adapting, but also new pathways to support and co-working.

Conclusion

The closure of vape shops appears to have most impacted smaller bricks and mortar shops affecting businesses by decline in customers and impacting staff (furlough). For those services that could stay open there may be lessons learned in how to support vulnerable and disadvantaged people who smoke by considering new pathways to support.
Over-expression of SRD5A3 and its prognostic significance in breast cancer
Authors: Zhang Yong-ping , Na Wen-ting , Dai Xiao-qiang , Li Ruo-fei , Wang Jian-xiong , Gao Ting , Zhang Wei-bo , Xiang Cheng
Published: August 2021

Objective

The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches.

Methods

We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed.

Results

Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P< 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (allP< 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P= 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P< 0.001), age (P< 0.05), and histologic subtype (P< 0.001) but had no significant relationship with other clinical characteristics (allP> 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (allP< 0.05).

Conclusions

SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.
A second hit somatic (p.R905W) and a novel germline intron-mutation of TSC2 gene is found in intestinal lymphangioleiomyomatosis: a case report with literature review
Authors: Han Bogyeong , Lee Juhwan , Kwak Yoon Jin , Kim Hyun-Young , Lee Kwang Hoon , Shim Yumi , Lee Hyunju , Park Sung-Hye
Published: August 2021

Background

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs associated with germline mutations in TSC1 and TSC2, including exonic, intronic, or mosaic mutations. Gastrointestinal (GI) tract Lymphangioleiomyomatosis (LAM) is an extremely rare manifestation of TSC, with few reported cases. Herein, we aimed to determine the driver mutation, pathogenesis, and relationship of germline and somatic mutations of LAM through whole-genome sequencing (WGS) of the tumor and blood samples and whole transcriptome sequencing (WTS) analysis.

Case presentation

A nine-year-old girl with a full-blown TSC presented with abdominal masses detected during a routine check-up. Resected intestinal masses were diagnosed as LAM by thorough pathological examination. Interestingly, the LAM presented a somatic TSC2 gene mutation in exon 24 (p.R905W, c.C2713T), and the patient had intron retention by a novel germline mutation in the intron region of TSC2 (chr16:2126489, C > G).

Conclusion

Our case suggests that intron retention by a single nucleotide intronic mutation of TSC2 is sufficient to develop severe manifestations of TSC, but the development of LAM requires an additional somatic oncogenic mutation of TSC2.
T cell exhaustion is associated with the risk of papillary thyroid carcinoma and can be a predictive and sensitive biomarker for diagnosis
Authors: Zhu Chumeng , Dai Yuechu , Zhang Hui , Ruan Yanyun , Zhou Yong , Dai Yingjie , Fan Lilong , Jia Tianjun , Lu Hongsheng , Chen Qi
Published: August 2021

Background

The incidence of papillary thyroid carcinoma (PTC) has been steadily increasing over the past decades. Hashimoto’s thyroiditis (HT) is the most common autoimmune disease, and is related to the pathogenesis of PTC. Programmed death-1 (PD-1) is currently used for the treatment of PTC, but there are very few studies on the clinical value of PD-1 in the diagnosis and targeted therapy of PTC.

Methods

The expression of T, B, NK cells and PD-1 in the peripheral blood of 132 patients with PTC (PTC group), 48 patients with nodular goiter (NG group) and 63 healthy subjects (HP group) were detected by flow cytometry. The expression of plasma T3, T4, FT3, FT4, TSH, TGAb and TPO was detected by chemiluminescence immunoassay. Among 132 PTC, 49 PTC&HT and 83 PTC&noHT were included. Among 48 NG, 10 NG&HT and 38 NG&noHT were included. The expressions of programmed death- ligand1(PD-L1) in tumor tissues of PTC group and thyroid tissues of NG group, PD-1 and CD3 in tumor infiltration lymphocyte (TIL) were detected by immunohistochemistry.

Results

The expression of FT3, TGAb, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC and NG was significantly higher than that in the HP group. Moreover, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ expression had significant differences between the PTC group and the NG group. In addition, the expression of TGAb, TPO, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC&HT group was significantly higher than that in the PTC&noHT group. While, the expression of B cells, CD3+PD-1+, CD3+CD4+PD-1+ and CD3+CD8+PD-1+ in PTC&HT group was higher than that in NG&HT group. PD-1 showed a significant correlation with PTC lymph node metastasis. CD3+PD-1+ and CD3+CD4+PD-1+ was higher in N1 stage than in N0 stage. Immunohistochemical results showed that the expression of PD-1, CD3 and PD-L1 in PTC was significantly higher than that in NG.

Conclusions

T cell exhaustion might act as a biomarker for the differential diagnosis of PTC and NG. Patients with PTC&HT have obvious T cell exhaustion and increased expression of PD-1, PD-L1.Targeting the PD-1/PD-L1 pathway could be a new approach to prevent malignant transformation from HT to PTC&HT in the future.
Lack of in-brace x-rays in compliant AIS patients wearing full-time TLSO braces associates with failure
Authors: Alvarez Isabel , Poppino Kiley , Karol Lori , McIntosh Amy L.
Published: August 2021

Background

In-brace correction and brace compliance with thoraco-lumbo-sacral orthotic (TLSO) braces are associated with successful treatment of adolescent idiopathic scoliosis (AIS). This paper compares patients who had consistent radiographic documentation of in-brace correction to those who did not.

Methods

All skeletally immature (Risser 0-2) patients were treated for AIS (25-45°) with full-time TLSO braces that had compliance temperature monitors. All patients wore their braces at least 12 h a day. Brace failure was defined as curve progression to a surgical magnitude (≥ 50°). All patients were followed until brace discontinuation.

Results

Ninety patients (F 82, M 8) with an average age of 12.1 (10.1-15.0) years, Risser grade 0 (0-2), BMI percentile 48.5 (0.0-98.8), and daily brace wear of 16.5 (12.1-21.6) h/day were treated for 24.3 (8.0-66.6) months. Patients went through 1.7 (1-4) braces on average. Forty-two out of 90 (46.7%) patients had some amount of brace time with an unknown in-brace correction, which, on average, was 66.1% of their total treatment course (11.5-100). On univariate analysis, patients that did not have a repeat in-brace x-ray with major brace adjustments or new brace fabrication tended to be more skeletally immature (Risser 0 and tri-radiate open, p = 0.028), wear more braces throughout their treatment (2.0 vs 1.4, p < 0.001), were treated for a longer period of time (27 vs 22 months, p = 0.022), and failed bracing more often (47.6% vs 22.9%, p = 0.014).

Conclusions

Patients who did not have new in-brace x-rays with major brace adjustments and/or new brace fabrication were 3.1 (95% CI 1.2-7.6) times more likely to fail bracing than patients who were re-checked with new in-brace x-rays.

Trial registration

ClinicalTrials.gov—NCT02412137, initial registration date April 2015

Level of evidence

III
Functional microRNA targetome undergoes degeneration-induced shift in the retina
Authors: Chu-Tan Joshua A. , Cioanca Adrian V. , Feng Zhi-Ping , Wooff Yvette , Schumann Ulrike , Aggio-Bruce Riemke , Patel Hardip , Rutar Matt , Hannan Katherine , Panov Konstantin , Provis Jan , Natoli Riccardo
Published: August 2021

Background

MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mRNA interactions in health and disease will provide important insight into the key pathways miRNA regulate in disease pathogenesis and may lead to potential therapeutic targets to mediate retinal degeneration.

Methods

To identify the active miRnome targetome interactions in the healthy and degenerating retina, AGO2 HITS-CLIP was performed using a rodent model of photoreceptor degeneration. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data was performed to identify the cellular location of AGO2 and key members of the microRNA targetome in the retina. AGO2 findings were verified by in situ hybridization (RNA) and immunohistochemistry (protein).

Results

Analysis revealed a similar miRnome between healthy and damaged retinas, however, a shift in the active targetome was observed with an enrichment of miRNA involvement in inflammatory pathways. This shift was further demonstrated by a change in the seed binding regions of miR-124-3p, the most abundant retinal AGO2-bound miRNA, and has known roles in regulating retinal inflammation. Additionally, photoreceptor cluster miR-183/96/182 were all among the most highly abundant miRNA bound to AGO2. Following damage, AGO2 expression was localized to the inner retinal layers and more in the OLM than in healthy retinas, indicating a locational miRNA response to retinal damage.

Conclusions

This study provides important insight into the alteration of miRNA regulatory activity that occurs as a response to retinal degeneration and explores the miRNA-mRNA targetome as a consequence of retinal degenerations. Further characterisation of these miRNA/mRNA interactions in the context of the degenerating retina may provide an important insight into the active role these miRNA may play in diseases such as AMD.