bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development of Sound Localization Latency in Infants and Young Children with Normal Hearing
Authors: Eklöf Martin , Asp Filip , Berninger Erik
Published: May 2022

With the advances in eye tracking, saccadic reflexes towards auditory stimuli have become an easily accessible behavioral response. The present study investigated the development of horizontal sound localization latency quantified by saccadic reflexes in infants and young children with normal hearing (0.55 to 5.6 years, n = 22). The subject was seated in front of an array of 12 loudspeaker/display-pairs arranged equidistantly in an arc from −55 to + 55° azimuth. An ongoing auditory-visual stimulus was presented at 63 dB SPL and shifted to another randomly selected pair at 24 occasions. At each shift, the visual part of the stimulus was blanked for 1.6 s providing auditory-only localization cues. A sigmoid model was fitted to the gaze samples following the azimuthal sound shifts. The overall sound localization latency (SLL) for a subject was defined as the mean of the latencies for all trials included by objective criteria. The SLL was assessed in 21 of 22 children with a mean of 6.1 valid trials. The SLL ranged 400 to 1400 ms (mean = 860 ms). An inverse model demonstrated a significant relationship between SLL and age ( R2 = 0.79, p < 0.001), reflecting a distinct reduction of latency with increasing age. No partial correlation between SLL and sound localization accuracy was found when controlling for age ( p = 0.5), suggesting that localization latency may provide diagnostic value beyond accuracy.
Knowledge and Attitude towards COVID-19 Vaccination and Associated Factors among College Students in Northwest Ethiopia, 2021
Authors: Aklil Mastewal Belayneh , Temesgan Wubedle Zelalem
Published: May 2022

Background

It is imperative to ensure optimal vaccine uptake at the population level to combat the deadly COVID-19 pandemic disease. However, refusal of the COVID-19 vaccine, poor knowledge, and a negative attitude towards vaccination are the challenges of the world. College students are among the high-risk subgroups of the population to COVID-19 infection and the main source of information and trust in vaccines to the society. Also, their judgement on vaccine affect the public attitude towards vaccination. Therefore, this study aimed to assess knowledge and attitude towards COVID-19 vaccination and associated factors among college students in Gondar city, northwest Ethiopia.

Methods

An institution-based cross-sectional study was conducted among 626 study participants in Gondar city. A multistage sampling technique was used to recruit the study participants. A pretested self-administered questionnaire was used to collect the data. Bivariable and multivariable logistic regression analyses were performed to assess factors associated with knowledge and attitude towards COVID-19 vaccination. The level of significance was claimed based on a p-value < 0.05.

Results

In this study, 46.8% (95% CI: 43.3, 50.6) of study participants had good knowledge and 50% (95% CI: 45.9, 53.7) had a positive attitude towards COVID-19 vaccination. Having comorbidity disease and being male were significantly associated with good knowledge. In addition, being married, being a health science student, being exposed to mass media, having a good knowledge of COVID-19 vaccination, and having paternal primary education were significantly associated with a positive attitude towards COVID-19 vaccination.

Conclusion

In general, knowledge and attitude towards COVID-19 vaccination among college students are low. Comorbidity disease and sex were predictors of COVID-19 vaccination knowledge, whereas, marital status, category of college students, mass media, paternal education and knowledge about COVID-19 vaccination were predictors of COVID-19 vaccination attitude. Alleviating participants’ concerns and improving their confidence through health education is crucial.
Who’s in the House? Staffing in Long-Term Care Homes Before and During COVID-19 Pandemic
Authors: Vellani Shirin , Zuniga Franziska , Spilsbury Karen , Backman Annica , Kusmaul Nancy , Scales Kezia , Chu Charlene H. , Mateos José Tomás , Wang Jing , Fagertun Anette , McGilton Katherine S.
Published: May 2022

Critical gaps exist in our knowledge on how best to provide quality person-centered care to long-term care (LTC) home residents which is closely tied to not knowing what the ideal staff is complement in the home. A survey was created on staffing in LTC homes before and during the COVID-19 pandemic to determine how the staff complement changed. Perspectives were garnered from researchers, clinicians, and policy experts in eight countries and the data provides a first approximation of staffing before and during the pandemic. Five broad categories of staff working in LTC homes were as follows: (1) those responsible for personal and support care, (2) nursing care, (3) medical care, (4) rehabilitation and recreational care, and (5) others. There is limited availability of data related to measuring staff complement in the home and those with similar roles had different titles making it difficult to compare between countries. Nevertheless, the survey results highlight that some categories of staff were either absent or deemed non-essential during the pandemic. We require standardized high-quality workforce data to design better decision-making tools for staffing and planning, which are in line with the complex care needs of the residents and prevent precarious work conditions for staff.
Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia
Authors: Maciocia Paul M. , Wawrzyniecka Patrycja A. , Maciocia Nicola C. , Burley Amy , Karpanasamy Thaneswari , Devereaux Sam , Hoekx Malika , O’Connor David , Leon Theresa , Rapoz-D’Silva Tanya , Pocock Rachael , Rahman Sunniyat , Gritti Giuseppe , Yánez Diana C. , Ross Susan , Crompton Tessa , Williams Owen , Lee Lydia , Pule Martin A. , Mansour Marc R.
Published: May 2022

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure compared with those in B cell acute lymphoblastic leukemia. The potent immunotherapeutic approaches applied in B cell acute lymphoblastic leukemia, which have revolutionized the treatment paradigm, have proven more challenging in T-ALL, largely due to a lack of target antigens expressed on malignant but not healthy T cells. Unlike B cell depletion, T-cell aplasia is highly toxic. Here, we show that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% of relapsed/refractory disease, and only on a small fraction (<5%) of normal T cells. Using cell line models and patient-derived xenografts, we found that chimeric antigen receptor (CAR) T-cells targeting CCR9 are resistant to fratricide and have potent antileukemic activity both in vitro and in vivo, even at low target antigen density. We propose that anti-CCR9 CAR-T cells could be a highly effective treatment strategy for T-ALL, avoiding T cell aplasia and the need for genome engineering that complicate other approaches.
Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia
Authors: Matthews Andrew H. , Perl Alexander E. , Luger Selina M. , Loren Alison W. , Gill Saar I. , Porter David L. , Babushok Daria V. , Maillard Ivan P. , Carroll Martin P. , Frey Noelle V. , Hexner Elizabeth O. , Martin Mary Ellen , McCurdy Shannon R. , Stadtmauer Edward A. , Paralkar Vikram R. , Bruno Ximena Jordan , Hwang Wei-Ting , Margolis David , Pratz  Keith W.
Published: May 2022

CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.
JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
Authors: Busquets Oriol , Espinosa-Jiménez Triana , Ettcheto Miren , Olloquequi Jordi , Bulló Mònica , Carro Eva , Cantero José Luis , Casadesús Gemma , Folch Jaume , Verdaguer Ester , Auladell Carme , Camins Antoni
Published: May 2022

Background and aim

The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements.

Methods

Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss.

Results

Our studies demonstrated that HFD in Jnk3−/− lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed.

Conclusions

Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.
EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes
Authors: Liu Xinyu , Li Conghui , Li Jiao , Xie Lesi , Hong Zeng , Zheng Kang , Zhao Xiaofeng , Yang Aifen , Xu Xiaofeng , Tao Huaping , Qiu Mengsheng , Yang Junlin
Published: May 2022

Background

The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known.

Methods

Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation.

Results

EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues.

Conclusions

These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.
A Type-2 Fuzzy Approach to Driver-Automation Shared Driving Lane Keeping Control of Semi-Autonomous Vehicles Under Imprecise Premise Variable
Authors: Liu Yue , Xu Qing , Guo Hongyan , Zhang Hui
Published: May 2022

The driver-automation shared driving is a transition to fully-autonomous driving, in which human driver and vehicular controller cooperatively share the control authority. This paper investigates the shared steering control of semi-autonomous vehicles with uncertainty from imprecise parameter. By considering driver’s lane-keeping behavior on the vehicle system, a driver-automation shared driving model is introduced for control purpose. Based on the interval type-2 (IT2) fuzzy theory, moreover, the driver-automation shared driving model with uncertainty from imprecise parameter is described using an IT2 fuzzy model. After that, the corresponding IT2 fuzzy controller is designed and a direct Lyapunov method is applied to analyze the system stability. In this work, sufficient design conditions in terms of linear matrix inequalities are derived, to guarantee the closed-loop stability of the driver-automation shared control system. In addition, an $$H_{\infty }$$

H
∞

performance is studied to ensure the robustness of control system. Finally, simulation-based results are provided to demonstrate the performance of proposed control method. Furthermore, an existing type-1 fuzzy controller is introduced as comparison to verify the superiority of the proposed IT2 fuzzy controller.
CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool
Authors: Shojaei Baghini Sadegh , Gardanova Zhanna R. , Abadi Saeme Azizi Hassan , Zaman Burhan Abdullah , İlhan Ahmet , Shomali Navid , Adili Ali , Moghaddar Roozbeh , Yaseri Amirhossein Fakhre
Published: May 2022

The progress of genetic engineering in the 1970s brought about a paradigm shift in genome editing technology. The clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system is a flexible means to target and modify particular DNA sequences in the genome. Several applications of CRISPR/Cas9 are presently being studied in cancer biology and oncology to provide vigorous site-specific gene editing to enhance its biological and clinical uses. CRISPR's flexibility and ease of use have enabled the prompt achievement of almost any preferred alteration with greater efficiency and lower cost than preceding modalities. Also, CRISPR/Cas9 technology has recently been applied to improve the safety and efficacy of chimeric antigen receptor (CAR)-T cell therapies and defeat tumor cell resistance to conventional treatments such as chemotherapy and radiotherapy. The current review summarizes the application of CRISPR/Cas9 in cancer therapy. We also discuss the present obstacles and contemplate future possibilities in this context.
Gaur genome reveals expansion of sperm odorant receptors in domesticated cattle
Authors: Low Wai Yee , Rosen Benjamin D. , Ren Yan , Bickhart Derek M. , To Thu-Hien , Martin Fergal J. , Billis Konstantinos , Sonstegard Tad S. , Sullivan Shawn T. , Hiendleder Stefan , Williams John L. , Heaton Michael P. , Smith Timothy P. L.
Published: May 2022

Background

The gaur (Bos gaurus) is the largest extant wild bovine species, native to South and Southeast Asia, with unique traits, and is listed as vulnerable by the International Union for Conservation of Nature (IUCN).

Results

We report the first gaur reference genome and identify three biological pathways including lysozyme activity, proton transmembrane transporter activity, and oxygen transport with significant changes in gene copy number in gaur compared to other mammals. These may reflect adaptation to challenges related to climate and nutrition. Comparative analyses with domesticated indicine (Bos indicus) and taurine (Bos taurus) cattle revealed genomic signatures of artificial selection, including the expansion of sperm odorant receptor genes in domesticated cattle, which may have important implications for understanding selection for male fertility.

Conclusions

Apart from aiding dissection of economically important traits, the gaur genome will also provide the foundation to conserve the species.
Anthocyanin regulatory networks in Solanum tuberosum L. leaves elucidated via integrated metabolomics, transcriptomics, and StAN1 overexpression
Authors: Bao Yanru , Nie Tengkun , Wang Dongdong , Chen Qin
Published: May 2022

Background

Anthocyanins, which account for color variation and remove reactive oxygen species, are widely synthesized in plant tissues and organs. Using targeted metabolomics and nanopore full-length transcriptomics, including differential gene expression analysis, we aimed to reveal potato leaf anthocyanin biosynthetic pathways in different colored potato varieties.

Results

Metabolomics analysis revealed 17 anthocyanins. Their levels varied significantly between the different colored varieties, explaining the leaf color differences. The leaves of the Purple Rose2 (PurpleR2) variety contained more petunidin 3-O-glucoside and malvidin 3-O-glucoside than the leaves of other varieties, whereas leaves of Red Rose3 (RedR3) contained more pelargonidin 3-O-glucoside than the leaves of other varieties. In total, 114 genes with significantly different expression were identified in the leaves of the three potato varieties. These included structural anthocyanin synthesis–regulating genes such as F3H, CHS, CHI, DFR, and anthocyanidin synthase and transcription factors belonging to multiple families such as C3H, MYB, ERF, NAC, bHLH, and WRKY. We selected an MYB family transcription factor to construct overexpression tobacco plants; overexpression of this factor promoted anthocyanin accumulation, turning the leaves purple and increasing their malvidin 3-o-glucoside and petunidin 3-o-glucoside content.

Conclusions

This study elucidates the effects of anthocyanin-related metabolites on potato leaves and identifies anthocyanin metabolic network candidate genes.
Improving clinical trials using Bayesian adaptive designs: a breast cancer example
Authors: Hong Wei , McLachlan Sue-Anne , Moore Melissa , Mahar Robert K.
Published: May 2022

Background

To perform virtual re-executions of a breast cancer clinical trial with a time-to-event outcome to demonstrate what would have happened if the trial had used various Bayesian adaptive designs instead.

Methods

We aimed to retrospectively “re-execute” a randomised controlled trial that compared two chemotherapy regimens for women with metastatic breast cancer (ANZ 9311) using Bayesian adaptive designs. We used computer simulations to estimate the power and sample sizes of a large number of different candidate designs and shortlisted designs with the either highest power or the lowest average sample size. Using the real-world data, we explored what would have happened had ANZ 9311 been conducted using these shortlisted designs.

Results

We shortlisted ten adaptive designs that had higher power, lower average sample size, and a lower false positive rate, compared to the original trial design. Adaptive designs that prioritised small sample size reduced the average sample size by up to 37% when there was no clinical effect and by up to 17% at the target clinical effect. Adaptive designs that prioritised high power increased power by up to 5.9 percentage points without a corresponding increase in type I error. The performance of the adaptive designs when applied to the real-world ANZ 9311 data was consistent with the simulations.

Conclusion

The shortlisted Bayesian adaptive designs improved power or lowered the average sample size substantially. When designing new oncology trials, researchers should consider whether a Bayesian adaptive design may be beneficial.
Mucosal healing of small intestinal stricture is associated with improved prognosis post-dilation in Crohn’s disease
Authors: Hibiya Shuji , Ohtsuka Kazuo , Takenaka Kento , Kawamoto Ami , Matsuyama Yusuke , Udagawa Yumi , Motobayashi Maiko , Shimizu Hiromichi , Fujii Toshimitsu , Saito Eiko , Nagahori Masakazu , Okamoto Ryuichi , Watanabe Mamoru
Published: May 2022

Background

Small intestinal stricture is a major cause for surgery in Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is performed for small intestinal strictures to avoid surgery, often repeatedly. However, factors that are associated with prognosis after EBD of small intestinal strictures remain poorly investigated. Mucosal healing is the therapeutic target in CD. We aimed to investigate the impact of mucosal healing defined by the presence of ulcers at the small intestinal stricture site on the prognosis of EBD in CD patients.

Methods

We retrospectively included patients with CD who underwent initial EBD for endoscopically impassable small intestinal strictures from January 2012 to March 2020 at a single center. The association between presence of ulcer at the stricture site and surgery after EBD was examined by Cox proportional hazards model.

Results

Of the 98 patients included, 63 (64.3%) had ulcer at the stricture site. 20 (31.7%) of these patients underwent surgery for the stricture in due course, whereas 4 (11.4%) of the patients without ulcer of the stricture underwent surgery. In multivariate analysis, patients with ulcer of the stricture had a significantly higher risk for surgery than those without ulcer (hazard ratio 4.84; 95% confidence interval 1.58–14.79).

Conclusion

Mucosal healing at the stricture site indicated a favorable prognosis after EBD for small intestinal strictures in CD.
Assessing socioeconomic inequalities in cognitive impairment among older adults: a study based on a cross-sectional survey in India
Authors: Muhammad T. , Srivastava Shobhit , Sekher T. V.
Published: May 2022

Background

The rapidly aging population is a major concern for countries, especially where cognitive health in older age is poor. The study examined the socioeconomic and health-related factors associated with cognitive impairment among older adults and the contribution of those factors to the concentration of low cognitive functioning among older adults from economically poor households.

Methods

Data this study were derived from the “Building Knowledge Base on Population Ageing in India” (BKPAI) survey, which was carried out in seven major states of India. The effective sample size for the analysis was 9176 older adults aged 60 years and above. Results from descriptive and bivariate analysis were reported in the initial stage. Multivariable logistic regression analysis was conducted to explore the associations. Additionally, the concentration index and concentration curve were used to measure socioeconomic inequality in cognitive impairment among older adults. Wagstaff decomposition was employed to explore the key contributors in the concentration index.

Results

Nearly 60% of older adults suffered from cognitive impairment in the study. The likelihood of cognitive impairment were higher among older adults with a low level of self-perceived income sufficiency [coefficient: 0.29; confidence interval (CI): 0.07- 0.52] compared to older adults with higher levels of perceived income status. Older adults with more than 10 years of schooling were less likely to be cognitively impaired [coefficient: -1.27; CI: − 1.50- -1.04] in comparison to those with no education. Cognitive impairment was concentrated among older adults from households with the lowest wealth quintile (concentration index (CCI): − 0.10: p < 0.05). Educational status explained 44.6% of socioeconomic inequality, followed by 31.8% by wealth status and 11.5% by psychological health. Apart from these factors, difficulty in instrumental activities of daily living (3.7%), caste (3.7%), and perceived income sufficiency to fulfil basic needs (3.0%) explained socioeconomic inequality in cognitive impairment among older adults.

Conclusions

Findings suggest that older adults with lower perceived income, lower levels of education, poor physical and mental health, and poor physical and social resources were more likely to be cognitively impaired. Education, wealth and psychological health are major contributors in socioeconomic inequality in late-life cognitive impairment, which may be target areas in future policy formulation to reduce the inequality in cognitive impairment in older Indian adults.
Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection
Authors: Chounta Vasiliki , Snedecor Sonya J. , Wu Sterling , Van de Velde Nicolas
Published: May 2022

Background

Efficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens.

Methods

An adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks (Q4W) vs SoC (ATLAS/FLAIR, n = 591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n = 327 per group). Eligible participants were virologically suppressed (viral load < 50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety assessments at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA < 50 copies/mL or ≥ 50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3–5 AEs excluding injection-site reactions. A subgroup analysis stratified by baseline third active drug class was performed.

Results

Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.

Conclusions

This analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC.

Trial registration: NCT02938520, NCT02951052, NCT03299049.
CRISPR-Cas12a combination to alleviate the false-positive in loop-mediated isothermal amplification-based diagnosis of Neisseria meningitidis
Authors: Trung Ngo Tat , Son Le Huu Phuc , Hien Trinh Xuan , Quyen Dao Thanh , Bang Mai Hong , Song Le Huu
Published: May 2022

Background

Loop isothermal amplification (LAMP) has recently been proposed as a point-of-care diagnostic tool to detect acute infectious pathogens; however, this technique embeds risk of generating false-positive results. Whereas, with abilities to accurately recognize specific sequence, the CRISPR/Cas12a can forms complexes with cognate RNA sensors and cleave pathogen’s DNA targets complimerntary to its cognate RNA, afterward acquiring the collateral activity to unbiasedly cut nearby off-target fragments. Therefore, if relevant fluorescent-quencher-nucleic probes are present in the reaction, the non-specific cleavage of probes releases fluorescences and establish diagnostic read-outs.

Methods

The MetA gene of N. meningitidis was selected as target to optimize the LAMP reaction, whereas pseudo-dilution series of N. meningitidis gemonics DNA was used to establish the detection limit of LAMP/Cas12a combination assay. The diagnostic performance of established LAMP/Cas12a combination assay was validated in comparation with standard real-time PCR on 51 CSF samples (14 N. meningitidis confirmed patients and 37 control subjects).

Results

In relevant biochemical conditions, CRISPR-Cas12a and LAMP can work synchronously to accurately identify genetics materials of Nesseria menitigistis at the level 40 copies/reaction less than 2 h.

Conclusions

In properly optimized conditions, the CRISPR-Cas12a system helps to alleviate false positive result hence enhancing the specificity of the LAMP assays.
The convoluted process of diagnosing pulmonary mycosis caused by Exophiala dermatitidis: a case report
Authors: Li Zhengtu , Tang Jianli , Zhu Jinping , Xie Mingzhou , Huang Shaoqing , Li Shaoqiang , Zhan Yangqing , Zeng Weiqi , Xu Teng , Ye Feng
Published: May 2022

Background

Etiological diagnosis is a key step in the treatment of patients with rare pulmonary mycosis, and the lack of understanding of this disease and lack of specific markers for the detection of rare species, such as Exophiala dermatitidis, add to the difficulty in diagnosing the condition. Therefore, improving the diagnostic strategies for this disease is very important.

Case presentation

A 52-year-old man presented with cough, sputum production and hemoptysis; chest computed tomography (CT) revealed multiple bilateral lesions. The pathogen was unable to be identified after three biopsies. Subsequently, we performed combined tissue metagenomic next-generation sequencing (mNGS). The results of mNGS and a good therapeutic response helped to identify the causative pathogen as Exophiala dermatitidis. Finally, the patient was diagnosed with Exophiala dermatitidis pneumonia.

Conclusions

Combining molecular techniques, such as mNGS, with clinical microbiological tests will improve the rate of positivity in the diagnosis of rare fungal infections, and the importance of follow-up should be emphasized.
Clinical management and outcomes of acute febrile illness in children attending a tertiary hospital in southern Ethiopia
Authors: Shimelis Techalew , Vaz Nery Susana , Tadesse Birkneh Tilahun , Bartlett Adam W. , Belay Fitsum W/Gebriel , Schierhout Gill , Dittrich Sabine , Crump John A. , Kaldor John M.
Published: May 2022

Background

The management of febrile illnesses is challenging in settings where diagnostic laboratory facilities are limited, and there are few published longitudinal data on children presenting with fever in such settings. We have previously conducted the first comprehensive study of infectious aetiologies of febrile children presenting to a tertiary care facility in Ethiopia. We now report on clinicians’ prescribing adherence with guidelines and outcomes of management in this cohort.

Methods

We consecutively enrolled febrile children aged 2 months and under 13 years, who were then managed by clinicians based on presentation and available laboratory and radiologic findings on day of enrolment. We prospectively collected outcome data on days 7 and 14, and retrospectively evaluated prescribing adherence with national clinical management guidelines.

Results

Of 433 children enrolled, the most common presenting syndromes were pneumonia and acute diarrhoea, diagnosed in 177 (40.9%) and 82 (18.9%), respectively. Antibacterial agents were prescribed to 360 (84.7%) of 425 children, including 36 (34.0%) of 106 children without an initial indication for antibacterials according to guidelines. Antimalarial drugs were prescribed to 47 (11.1%) of 425 children, including 30 (7.3%) of 411 children with negative malaria microscopy. Fever had resolved in 357 (89.7%) of 398 children assessed at day 7, and in-hospital death within 7 days occurred in 9 (5.9%) of 153 admitted patients. Among children with pneumonia, independent predictors of persisting fever or death by 7 days were young age and underweight for age. Antibacterial prescribing in the absence of a guideline-specified indication (overprescribing) was more likely among infants and those without tachypnea, while overprescribing antimalarials was associated with older age, anaemia, absence of cough, and higher fevers.

Conclusion

Our study underscores the need for improving diagnostic support to properly guide management decisions and enhance adherence by clinicians to treatment guidelines.
The prevalence of Fabry disease in a statewide chronic kidney disease cohort – Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study
Authors: Mallett Andrew , Kearey Phoebe Jane , Cameron Anne , Healy Helen G. , Denaro Charles , Thomas Mark , Lee Vincent W. , Stark Samantha Louise , Fuller Maria , Wang Zaimin , Hoy Wendy E.
Published: May 2022

Background

Prevalence of Fabry disease amongst Chronic Kidney Disease (CKD) patients on haemodialysis has been shown to be approximately 0.2%.

Methods

We undertook a cross-sectional study employing a cascade screening strategy for Fabry Disease amongst 3000 adult, male and female patients affected by CKD stage 1-5D/T at public, specialty renal practices within participating Queensland Hospital and Health Services from October 2017 to August 2019. A multi-tiered FD screening strategy, utilising a combination of dried blood spot (DBS) enzymatic testing, and if low, then lyso-GB3 testing and DNA sequencing, was used.

Results

Mean (SD) age was 64.0 (15.8) years (n = 2992), and 57.9% were male. Eight participants withrew out of the 3000 who consented. Of 2992 screened, 6 (0.20%) received a diagnosis of FD, 2902 (96.99%) did not have FD, and 84 (2.81%) received inconclusive results. Of the patients diagnosed with FD, mean age was 48.5 years; 5 were male (0.29%) and 1 was female (0.08%); 4 were on kidney replacement therapy (2 dialysis and 2 transplant); 3 were new diagnoses.

Conclusions

Estimated overall FD prevalence was 0.20%. Screening of the broader CKD population may be beneficial in identifying cases of FD.

Trial registration

The aCQuiRE Study has been prospectively registered with the Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au) as pj09946 (Registered 3rd July 2017).
Postoperative radiotherapy for meningiomas – a decision-making analysis
Authors: Fischer Galina Farina , Brügge Detlef , Andratschke Nicolaus , Baumert Brigitta Gertrud , Bosetti Davide Giovanni , Caparrotti Francesca , Herrmann Evelyn , Papachristofilou Alexandros , Rogers Susanne , Schwyzer Lucia , Zwahlen Daniel Rudolf , Hundsberger Thomas , Putora Paul Martin
Published: May 2022

Background

The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized.

Methods

Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine.

Results

Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous.

Conclusions

Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals.
Modified suture-assisted canaloplasty in Asians with primary open-angle glaucoma: a prospective study with 12-month follow-up
Authors: Liang Ya , Yu Qiuli , Sun Hong , Sucijanti  , Gu Liuwei , Yuan Zhilan
Published: May 2022

Background

To evaluate the efficacy and safety of modified suture-assisted canaloplasty in Asians with primary open-angle glaucoma (POAG).

Methods

A prospective, consecutive cases study, evaluating a modified canaloplasty by twisted 6/0 suture was performed on Asian POAG patients. Three modifications of this canaloplasty included opening the Schlemm’s canal by viscocanalostomy, circumferential probing by a twisted 6/0 suture and loose suture of the superficial scleral flap. The twisted 6/0 suture was selected as a prober based on characteristical analysis of size and contact measurement as well as chemical composition conducted among 5/0, twisted 6/0 polypropylene sutures and the microcatheter. Success criteria were defined as intraocular pressure (IOP) ≤ 21 mmHg, 18 mmHg, 15 mmHg, and ≥ 20% reduction without (complete success) or with medications (qualified success). Efficacy was assessed by the success rate of circumferential catheterization, IOP values, the success rate of the surgery, the number of IOP-lowering medications, best-corrected vision acuity (BCVA), cup-to-disc ratio (C/D), and mean deviation (MD). Safety was evaluated by adverse events.

Results

Forty eyes from 40 consecutive patients were included with a mean follow-up of 14.8 ± 3.0 months. Circumferential catheterization was successfully conducted in 36 eyes (90%). Mean IOP decreased from 26.2 ± 6.9 mmHg to 14.5 ± 2.7 mmHg at 12 months postoperatively. While medication numbers were reduced from 3.2 ± 0.6 to 0.5 ± 0.8 at month 12 (both p < 0.001). Qualified success rate was 97.2% [95% confidence interval (CI) 0.92–1.03], 86.1% (95% CI 0.74–0.98) and 66.7% (95% CI 0.51–0.83) at 12 months with three criteria. BCVA, C/D and MD did not show progression at 1-year follow-up (p > 0.05). Age, baseline IOP, and spherical equivalent negatively influenced the success rate significantly (all p < 0.05). Adverse events included hyphema (30.6%), IOP spike > 25 mmHg (8.3%), and peripheral synechia to the trabecular-Descemet’s membrane (2.7%).

Conclusion

Twisted 6/0 suture can be an ideal material for cannulation. Modified suture-assisted canaloplasty is an effective, safe alternative with a cost-efficient feature for patients with POAG, especially in developing countries.

Trial registration

This trial was registered in the Chinese Clinical Trial Registry (ChiCTR1900028618, 29/12/2019).
Peripheral and neural correlates of self-harm in children and adolescents: a scoping review
Authors: Sparrow-Downes Victoria M. , Trincao-Batra Sara , Cloutier Paula , Helleman Amanda R. , Salamatmanesh Mina , Gardner William , Baksh Anton , Kapur Rishi , Sheridan Nicole , Suntharalingam Sinthuja , Currie Lisa , Carrie Liam D. , Hamilton Arthur , Pajer Kathleen
Published: May 2022

Background

Self-harm in children and adolescents is difficult to treat. Peripheral and neural correlates of self-harm could lead to biomarkers to guide precision care. We therefore conducted a scoping review of research on peripheral and neural correlates of self-harm in this age group.

Methods

PubMed and Embase databases were searched from January 1980-May 2020, seeking English language peer-reviewed studies about peripheral and neural correlates of self-harm, defined as completed suicide, suicide attempts, suicidal ideation, or non-suicidal self-injury (NSSI) in subjects, birth to 19 years of age. Studies were excluded if only investigating self-harm in persons with intellectual or developmental disability syndromes. A blinded multi-stage assessment process by pairs of co-authors selected final studies for review. Risk of bias estimates were done on final studies.

Results

We screened 5537 unduplicated abstracts, leading to the identification of 79 eligible studies in 76 papers. Of these, 48 investigated peripheral correlates and 31 examined neural correlates. Suicidality was the focus in 2/3 of the studies, with NSSI and any type of self-harm (subjects recruited with suicidality, NSSI, or both) investigated in the remaining studies. All studies used observational designs (primarily case-control), most used convenience samples of adolescent patients which were predominately female and half of which were recruited based on a disorder. Over a quarter of the specific correlates were investigated with only one study. Inter-study agreement on findings from specific correlates with more than one study was often low. Estimates of Good for risk of bias were assigned to 37% of the studies and the majority were rated as Fair.

Conclusions

Research on peripheral and neural correlates of self-harm is not sufficiently mature to identify potential biomarkers. Conflicting findings were reported for many of the correlates studied. Methodological problems may have produced biased findings and results are mainly generalizable to patients and girls. We provide recommendations to improve future peripheral and neural correlate research in children and adolescents, ages 3-19 years, with self-harm.
Differences in personality functioning impairment in mood, anxiety, and personality disorders: a cluster analysis
Authors: Doubková Nikola , Heissler Radek , Preiss Marek , Sanders Edel
Published: May 2022

Background

The Alternative DSM-5 Model for Personality Disorders and the latest eleventh version of the International Classification of Diseases implement the level of impairment in self and interpersonal personality functioning (Level of Personality Functioning Scale - LPFS) as a core feature of personality pathology. However, some studies have indicated that personality functioning is also impaired in other mental disorders, but a more thorough exploration is missing. Thus, this study aims to develop profiles of levels of personality functioning in people with personality disorders and some other psychiatric diagnoses as well as without diagnosis.

Methods

One-hundred-forty-nine people participated in the study. They came from three groups – healthy controls (n = 53), people with personality disorders (n = 58), and people with mood and anxiety disorders (n = 38). The LPFS was assessed by the Semi-structured Interview for Personality Functioning DSM-5 (STiP-5.1). An optimal clustering solution using agglomerative hierarchical cluster analysis was generated to represent profiles of personality functioning.

Results

The two patient groups showed significantly higher levels of personality functioning impairment than healthy controls. People with personality disorders showed higher levels of impairment than the other groups. In addition, the clustering analysis revealed three distinct profiles of personality functioning.

Conclusions

The impairment of personality functioning seems to be useful in the clinical assessment of other than personality disorders as well. As the resulting clustering profiles suggest, LPFS can be seen as an overall indicator of the severity of mental health difficulties and the presence of mental disorders symptoms. The LPFS provides valuable and detailed information about the individual’s mental health and can thus serve as a broad basis for case formulation, treatment and therapy planning, and prognosis.
The COV-ED Survey: exploring the impact of learning and teaching from home on parent/carers’ and teachers’ mental health and wellbeing during COVID-19 lockdown
Authors: Connor C , De Valliere N , Warwick J , Stewart-Brown S , Thompson A
Published: May 2022

Background

Following the emergence of COVID-19 in the UK, on March 18th2020 the majority of schools in England closed and families and teachers were tasked with providing educational support for children and adolescents within the home environment. Little is known, however, regarding the impact of remote teaching and learning on the mental wellbeing of parents/carers and teaching staff.

Methods

The Coronavirus Education (COV-ED) online survey explored the practicalities of learning and teaching from home for 329 parents/carers and 117 teachers of 11–15 year old adolescents in England, during June/July 2020, and the associated impact on their mental wellbeing. Participants were recruited through schools and via University of Warwick social media channels. Data was analysed using a series of Multiple Linear and Multivariate Regressions.

Results

Despite coping well with the challenges of remote learning, a third of teachers reported below average mental wellbeing on the Warwick-Edinburgh Mental Wellbeing Scale. Multivariate regression revealed that wellbeing was associated with access to resources and confidence to teach from home. Almost half of parents/carers surveyed reported below average wellbeing. Multivariate regression revealed that poor wellbeing was more common in those who were also working from home and who lacked support for their own mental health. Concerns about their child’s mental health and lack of access to electronic devices and workspace were also significantly associated with the mental wellbeing of parents/carers.

Conclusions

Whilst young people’s mental health and wellbeing has, and continues to be a national priority, the mental health and wellbeing of the families and teachers supporting them has not previously been explored. Our survey population was of predominantly white British heritage, female and living in the West Midlands UK, therefore, findings should be treated with caution. Findings provide a snapshot of factors that may be of significance to families and schools in supporting the mental wellbeing of those tasked with learning from home. They will help i) increase knowledge and awareness with regard to future support of families and teachers during similar crises; ii) enable the design and development of practical solutions in the delivery of remote teaching and learning; and, iii) help address the mental wellbeing needs of those tasked with supporting adolescents.