bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased social interaction in Shank2-deficient mice following acute social isolation
Authors: Choi Ja Eun , Kaang Bong-Kiun
Published: April 2023

Autism spectrum disorder (ASD) is neuropsychiatric disorder with a gender specific risk. Although social impairment in ASD is one of the well characterized phenotypes, loneliness issue resides in patients with ASD and emerging reports show gender distribution in symptoms. Acute social isolation increases the motivation to socially interact in a gender-dependent manner, as only the male mice show increase in sociability following isolation. However, it remains to be explored whether the effects of loneliness in ASD differ between genders. Here, we used Shank2-deficient (Shank2−/−) mice, one of the animal models of ASD, to examine the sociability changes after acute social isolation. While only the male wild-type (WT) mice display increased sociability following 24-h isolation, both sexes of Shank2−/− mice show an increase in social interaction following isolation. These observations provide evidence that animal models of ASD have the sensitivity to acute social isolation and further show the motivation to socially interact.
Diminished ovarian reserve may not be associated with a poorer fresh cycle outcome in women < 38 years
Authors: Jin Huizi , Yan Enqi , Chen Dan , Zhao Mengya , Peng Wenju , Guo Yaxin , Jin Lei
Published: April 2023

Background

Previous studies have discussed the pregnancy outcomes of diminished ovarian reserve (DOR) patients. However, data on embryonic development potential, neonatal outcomes, and maternal complications of DOR patients still remained unknown. This is the first study to investigate the risk of DOR on pregnancy and perinatal outcomes among women < 38 years.

Methods

Retrospective cohort study was conducted. Patients (< 38 years of age) undergoing their first oocyte retrieval cycle were included. Patients were divided into DOR group and non-DOR group. Pregnancy outcomes of fresh cycle and cumulative live birth rate and perinatal outcomes after one oocyte retrieved cycle were compared between DOR and non-DOR group.

Result(s)

From January 2016 to September 2020, there were 8,179 patients involved: 443 patients in the DOR group and 7,736 patients in the non-DOR group. The incidences of live birth and clinical pregnancy did not differ significantly between patients with or without DOR after fresh cycle transfer, but the cumulative live birth rate was significantly lower in DOR group. Among women who had singleton live births, after binary logistic regression, the rates of maternal complications and neonatal outcomes were comparable in the two groups.

Conclusion(s)

DOR patients (< 38 years of age) showed similar pregnancy outcomes in the first fresh embryo transfer cycle but a lower chance of live birth after a whole oocyte retrieval cycle to non-DOR patients and DOR is not associated with adverse perinatal outcomes.
Psycho-emotional distress in children and adolescents in relation to COVID-19 confinement and pandemic: A systematized review
Authors: García-Rodríguez Mª Teresa , Juanatey-Rodríguez Iria , Seijo-Bestilleiro Rocío , González-Martin Cristina
Published: April 2023

A stressor such as a pandemic is a trigger to focus on the study of the psycho-emotional impact on children and adolescents from a nursing care perspective. The aim of this systematized review was to know the impact of the lockdown and COVID-19 pandemic on children (from 2 to 12 years) and adolescent (from 13 to 18 years) in relation to daily routines, as well as the most frequent psycho-emotional manifestations. The research was carried out following PRISMA guidelines and was performed using several databases (PubMed, Scopus and Cochrane). The search was focused on children and adolescent population between 2020 and 2021.The literature search was from November to December 2021. Sixteen articles were used to perform the systematized review. A disruption in daily routines and an increase in psycho-emotional manifestations have been observed in young people, which is understood as a worsening of their psycho-emotional integrity. Higher levels of anxiety and depression in adolescents and hyperactivity and dependence disorders in the children have also been reported. In conclusion, children and adolescents have been affected in the psycho-emotional sphere in the same way as adults, therefore, it is necessary to know the presenting characteristics of this group of people in order to be able to establish an effective nursing approach and help preserve the mental integrity, as well as promote resilience.
Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients: a retrospective study with inverse probability of treatment weighting analysis
Authors: Viana Marina Verçoza , Pellegrini José Augusto Santos , Perez Amanda Vilaverde , Schwarz Patrícia , da Silva Daiandy , Teixeira Cassiano , Gazzana Marcelo Basso , Rech Tatiana Helena
Published: April 2023

Background

Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality.

Methods

This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use.

Results

We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24–1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21–1.78).

Conclusions

Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.
VR-SOAP, a modular virtual reality treatment for improving social activities and participation of young people with psychosis: a study protocol for a single-blind multi-centre randomized controlled trial
Authors: Meins Ivo Alexander , Muijsson-Bouwman Dauw Catharina , Nijman Saskia Anne , Greaves-Lord Kirstin , Veling Wim , Pijnenborg Gerdina Hendrika Maria , van der Stouwe Elisabeth Christine Dorothée
Published: April 2023

Background

Young people with a psychotic disorder have the same social goals as their healthy peers, but their social networks are smaller, they participate less often in leisure activities and are less successful in work and education. Causes of these problems are multifaceted, but culminate in difficulties with interacting in daily life social situations. Current treatments have only moderate effects on social functioning and often target one specific domain. Virtual reality (VR) has the potential to improve the treatment of social interaction difficulties. We developed a modular VR treatment for social functioning and participation (VR-SOAP). In this study, the effect of this intervention will be investigated in a randomized controlled trial (RCT).

Methods

A total of 116 participants (age 18–40) with a DSM-5 diagnosis of schizophrenia spectrum or other psychotic disorder and problems with social functioning will be recruited from mental healthcare institutes in the Netherlands. Participants will be randomized to the experimental condition (VR-SOAP) or active VR control condition (VRelax). VR-SOAP consists of 14 sessions and 5 modules addressing causes of impaired social functioning: four optional modules (1–4) and one fixed module (5). Vrelax consists of 14 sessions that entail psychoeducation, stress management, relaxation techniques, and the exploration of relaxing environments in VR. Primary outcomes are quantity and quality of social contacts, leisure activities and social participation, measured with the experience sampling method (ESM). Secondary outcomes are psychiatric symptoms, social behaviour, social cognition, self-esteem, self-stigma and paranoid thoughts. Treatment effects will be compared at pre-treatment (baseline), post-treatment and at 6-month follow-up.

Discussion

If VR-SOAP proves to be effective, it provides therapists with a much-needed tool to improve social functioning of young adults with a psychotic disorder. Additionally, since the treatment consists of multiple modules targeting different transdiagnostic factors, this trial might provide input for new treatments to improve social functioning in a range of symptoms and disorders, e.g. mood, autism spectrum and anxiety disorders.

Trial registration

On the 10th of November 2021, this trial was registered prospectively in the Dutch Trial Register as NL9784.
Solubility and thermodynamic study of deferiprone in propylene glycol and ethanol mixture
Authors: Radmand Samira , Rezaei Homa , Zhao Hongkun , Rahimpour Elaheh , Jouyban Abolghasem
Published: April 2023

This work aims to obtain the solubility, density and thermodynamic parameters of deferiprone in propylene glycol and ethanol. For this purpose, a shake-flask technique was applied for solid–liquid equilibration and the spectrophotometry method was employed for solubility measurement. Solubility and density of deferiprone in non-aqueous mixtures of propylene glycol and ethanol were measured in the temperatures 293.2–313.2 K. Some equations including van’t Hoff, the Jouyban-Acree, the Jouyban-Acree-van’t Hoff, the mixture response surface and modified Wilson equations were used for the mathematical data modeling. The apparent thermodynamic parameters of the deferiprone dissolution process were computed and reported.
Changes in homocysteine and non-mercaptoalbumin levels after acute exercise: a crossover study
Authors: Shinagawa Akiho , Yamazaki Tomoki , Minematsu Ayako , Serizawa Naho , Hosoi Yuri , Ninomiya Yusuke , Miyakoshi Yuichi , Yano Tomohiro , Ota Masako
Published: April 2023

Background

Acute exercise is one factor that increases blood homocysteine levels, and elevated homocysteine levels cause oxidative stress. Albumin, which is abundant in blood, is an antioxidant, and the redox state of albumin is used as an index of oxidative stress in blood. This study aimed to assess the effect of acute exercise on plasma homocysteine levels and the blood non-mercaptoalbumin/mercaptoalbumin ratio as an oxidative stress marker.

Methods

This study used a crossover design with exercise and control conditions. Under exercise conditions, a bicycle ergometer was used to perform 40 min of transient constant-load exercise at 65% heart rate reserve. Under control conditions, participants rested for 40 min. Blood was collected before, 30 min after, and 90 min after exercise, and at the same time points under control conditions. Samples were analyzed for the homocysteine concentration and non-mercaptoalbumin/mercaptoalbumin ratio.

Results

The results revealed that a 65% heart rate reserve and 40 min of acute exercise increased plasma homocysteine concentration and non-mercaptoalbumin ratio. In the intra-condition comparison, the plasma Hcy concentration was significantly increased at Post 30 min (+ 0.83 ± 0.70 µmol/L, P = 0.003) compared with that at Pre in the exercise condition. Furthermore, 90 min after exercise, the blood non-mercaptoalbumin ratio was significantly increased (+ 0.35 ± 0.71%, P = 0.030) compared to Pre.

Conclusion

These results indicate that the plasma Hcy concentration first increased, and then the non-mercaptoalbumin/mercaptoalbumin ratio increased as the elevated state was maintained. This study revealed that 65% heart rate reserve, 40 min of acute exercise increased plasma Hcy concentration and non-mercaptoalbumin ratio.
Evaluation of hand functions and distal radioulnar joint instability in elite wheelchair basketball athletes: a cross-sectional pilot study
Authors: Yuine Hiroshi , Mutsuzaki Hirotaka , Yoshii Yuichi , Shimizu Yukiyo , Ishida Natsuki , Yasuda Taku , Iwai Koichi , Hotta Kazushi , Shiraishi Hideki , Tachibana Kaori
Published: April 2023

Background

Wrist injury affects wheelchair basketball players’ performance; however, the relationship between distal radioulnar joint (DRUJ) instability and hand functions is unclear. This cross-sectional pilot study investigated DRUJ instability in elite female wheelchair basketball athletes using force-monitor ultrasonography.

Methods

Nine elite female wheelchair basketball athletes (18 wrists) were included in the study. A triangular fibrocartilage complex (TFCC) injury was confirmed using magnetic resonance imaging (MRI). Hand functions were evaluated based on the range of motion (ROM) of wrist palmar flexion, dorsiflexion, radial deviation, and ulnar deviation; grip strength; arm circumference; forearm circumference; and DRUJ instability or pain using the ballottement test. The Mann–Whitney U test was used to compare parameters between the TFCC-injured and intact wrists. Radioulnar displacement was measured using force-monitor ultrasonography and pressure data, and the displacement-to-force ratio was used as an indicator of DRUJ instability. The correlation between the DRUJ displacement-to-force ratio and each hand function assessment was evaluated using Pearson correlation coefficient for the TFCC-injured and intact wrists. A generalized linear mixed model (GLMM) was used to estimate the relationship between hand functions and DRUJ instability.

Results

TFCC injuries in seven wrists were confirmed using MRI findings (38.9%). The ulnar deviation ROM values of the TFCC-injured wrist (n = 7) and intact (n = 11) groups were 38.6 ± 8.0° and 48.6 ± 7.8°, respectively. The ulnar deviation ROM was significantly smaller in the TFCC-injured wrists (p = 0.02, r = − 0.54). In the TFCC-injured wrists, no correlation was observed between the displacement-to-force ratio and the hand function assessment. In contrast, the displacement-to-force ratio negatively correlated with grip strength, arm circumference, and forearm circumference in the intact wrists (Pearson correlation coefficient r = − 0.78, − 0.61, and − 0.74, respectively). The GLMM showed that the displacement-to-force ratio significantly affected grip strength, arm circumference, and forearm circumference in the intact group.

Conclusions

In intact wrists, correlations were observed between hand functions such as upper arm/forearm strength and DRUJ stability evaluated using ultrasound. Maintaining and strengthening grip strength, forearm circumference, and arm circumference are associated with DRUJ stability and may be related to TFCC injury prevention in wheelchair basketball athletes.

Trial registration: The protocol was registered with the UMIN Clinical Trials Registry (UMIN000043343) [Date of first registration: 16/02/2021].
Bromodomain inhibitor i-BET858 triggers a unique transcriptional response coupled to enhanced DNA damage, cell cycle arrest and apoptosis in high-grade ovarian carcinoma cells
Authors: Quintela Marcos , James David W. , Pociute Agne , Powell Lydia , Edwards Kadie , Coombes Zoe , Garcia Jetzabel , Garton Neil , Das Nagindra , Lutchman-Singh Kerryn , Margarit Lavinia , Beynon Amy L. , Rioja Inmaculada , Prinjha Rab K. , Harker Nicola R. , Gonzalez Deyarina , Conlan R. Steven , Francis Lewis W.
Published: April 2023

Background

Ovarian cancer has a specific unmet clinical need, with a persistently poor 5-year survival rate observed in women with advanced stage disease warranting continued efforts to develop new treatment options. The amplification of BRD4 in a significant subset of high-grade serous ovarian carcinomas (HGSC) has led to the development of BET inhibitors (BETi) as promising antitumour agents that have subsequently been evaluated in phase I/II clinical trials. Here, we describe the molecular effects and ex vivo preclinical activities of i-BET858, a bivalent pan-BET inhibitor with proven in vivo BRD inhibitory activity.

Results

i-BET858 demonstrates enhanced cytotoxic activity compared with earlier generation BETis both in cell lines and primary cells derived from clinical samples of HGSC. At molecular level, i-BET858 triggered a bipartite transcriptional response, comprised of a ‘core’ network of genes commonly associated with BET inhibition in solid tumours, together with a unique i-BET858 gene signature. Mechanistically, i-BET858 elicited enhanced DNA damage, cell cycle arrest and apoptotic cell death compared to its predecessor i-BET151.

Conclusions

Overall, our ex vivo and in vitro studies indicate that i-BET858 represents an optimal candidate to pursue further clinical validation for the treatment of HGSC.
Epigenetically regulated gene expression profiles decipher four molecular subtypes with prognostic and therapeutic implications in gastric cancer
Authors: Weng Siyuan , Li Minghao , Deng Jinhai , Xu Hui , Ren Yuqing , Zhou Zhaokai , Wang Libo , Zhang Yuyuan , Xing Zhe , Li Lifeng , Liu Zaoqu , Han Xinwei
Published: April 2023

Background

Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract which seriously endangers the health of human beings worldwide. Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of GC. This study aimed to investigate the impact of epigenetically regulated genes on the prognosis, immune microenvironment, and potential treatment of GC.

Results

Under the premise of verifying significant co-regulation of the aberrant frequencies of microRNA (miRNA) correlated (MIRcor) genes and DNA methylation-correlated (METcor) genes. Four GC molecular subtypes were identified and validated by comprehensive clustering of MIRcor and METcor GEPs in 1521 samples from five independent multicenter GC cohorts: cluster 1 was characterized by up-regulated cell proliferation and transformation pathways, with good prognosis outcomes, driven by mutations, and was sensitive to 5-fluorouracil and paclitaxel; cluster 2 performed moderate prognosis and benefited more from apatinib and cisplatin; cluster 3 was featured by an up-regulated ligand–receptor formation-related pathways, poor prognosis, an immunosuppression phenotype with low tumor purity, resistant to chemotherapy (e.g., 5-fluorouracil, paclitaxel, and cisplatin), and targeted therapy drug (apatinib) and sensitive to dasatinib; cluster 4 was characterized as an immune-activating phenotype, with advanced tumor stages, benefit more from immunotherapy and displayed worst prognosis.

Conclusions

According to the epigenetically regulated GEPs, we developed four robust GC molecular subtypes, which facilitated the understanding of the epigenetic mechanisms underlying GC heterogeneity, offering an optimized decision-making and surveillance platform for GC patients.
Right and left ventricular blood pool T2 ratio on cardiac magnetic resonance imaging correlates with hemodynamics in patients with pulmonary hypertension
Authors: Deng Mei , Liu Anqi , Xu Wenqing , Yang Haoyu , Gao Qian , Zhang Ling , Zhen Yanan , Liu Xiaopeng , Xie Wanmu , Liu Min
Published: April 2023

Objectives

Our objective is to compare the right/left ventricular blood pool T1 ratio (RVT1/LVT1), and right/left ventricular blood pool T2 ratio (RVT2/LVT2) on Cardiac Magnetic Resonance Imaging (CMR) between patients with pulmonary hypertension (PH) and normal controls, to analyze the correlation of RVT1/LVT1, RVT2/LVT2 and hemodynamics measured with right heart catheterization (RHC) in patients with PH.

Methods

Forty two patients with PH and 40 gender-and age-matched healthy controls were prospectively included. All patients underwent RHC and CMR within 24 h. The right and left ventricular blood pool T1 and T2 values were respectively measured, and RVT1/LVT1 and RVT2/LVT2 between the PH group and the healthy control were compared. Meanwhile, the correlation between RVT1/LVT1, RV/LVT2 ratio and hemodynamic parameters in patients with PH respectively was analyzed.

Results

In the control group, RVT2 was significantly lower than LVT2 (t = 6.782, p < 0.001) while RVT1 also was lower than LVT1 (t = 8.961, p < 0.001). In patients with PH, RVT2 was significantly lower than LVT2 (t = 9.802, p < 0.001) while RVT1 was similar to LVT1 (t =  − 1.378, p = 0.176). RVT2/LVT2 in the PH group was significantly lower than that in the control group (p < 0.001). RVT1/LVT1 in PH patients increased in comparison with the control group (p < 0.001). RVT2/LVT2 negatively correlated with pulmonary vascular resistance (r =  − 0.506) and positively correlated with cardiac index (r = 0.521), blood oxygen saturation in Superior vena cava, right atrium, right ventricle and pulmonary artery (r = 0.564, 0.603, 0.648, 0.582).

Conclusions

RVT2/LVT2 on T2 mapping could be an additional CMR imaging marker that may assist to evaluate the severity of PH.
A systematic review, umbrella review, and quality assessment on clinical translation of stem cell therapy for knee osteoarthritis: Are we there yet?
Authors: Shang Zhizhong , Wanyan Pingping , Zhang Baolin , Wang Mingchuan , Wang Xin
Published: April 2023

Background

The success of stem cell therapy for knee osteoarthritis (KOA) in preclinical animal models has accelerated the pace of clinical translation. However, it remains uncertain whether the current scientific evidence supports the clinical application of stem cells in treating KOA. A comprehensive evaluation of the safety and efficacy of stem cell therapies and scientific evidence quality is necessary.

Methods

Using “stem cells” and “knee osteoarthritis” as the search terms, several databases, including PubMed, Web of Science, Cochrane, Embase, and Clinicaltrials.gov, were searched on August 25, 2022, and updated on February 27, 2023. Clinical studies that reported adverse reactions (ARs) of stem cell therapy in KOA patients were included without limiting the type of studies. Quantitative systematic reviews of stem cell therapy for KOA that conducted meta-analysis were included. Two researchers conducted literature screening and data extraction independently, and the evidence quality was evaluated according to the Institute of Health Economics and AMSTAR 2 criteria.

Results

Fifty clinical studies and 13 systematic reviews/meta-analyses (SRs/MAs) were included. Nineteen ARs were reported in 50 studies, including five knee-related ARs, seven common ARs, and seven other ARs. Some studies reported over 10% prevalence of knee pain (24.5%; 95% CI [14.7%, 35.7%]), knee effusion (12.5%; 95% CI [4.8%, 22.5%]), and knee swelling (11.9%; 95% CI [3.5%, 23.5%]). Additionally, two studies have reported cases of prostate cancer and breast tumors, respectively. However, these two studies suggest that stem cell therapy does not bring significant ARs to patients. SRs/MAs results revealed that stem cell therapy relieved pain in patients over time but did not improve knee function. However, current clinical studies have limited evidence regarding study objectives, test designs, and patient populations. Similarly, SRs/MAs have inadequate evidence regarding study design, risk of bias assessment, outcome description, comprehensive discussion, and potential conflicts of interest.

Conclusions

The inefficacy of stem cells, the risk of potential complications, and the limited quality of evidence from current studies precluded any recommendation for using stem cell products in patients with KOA. Clinical translation of stem cell therapies remains baseless and should be cautiously approached until more robust evidence is available.

PROSPERO registration number: CRD42022355875.
Conducting separate reviews of benefits and harms could improve systematic reviews and meta-analyses
Authors: Mayo-Wilson Evan , Qureshi Riaz , Li Tianjing
Published: April 2023

Guidance for systematic reviews of interventions recommends both benefits and harms be included. Systematic reviews may reach conclusions about harms (or lack of harms) that are not true when reviews include only some relevant studies, rely on incomplete data from eligible studies, use inappropriate methods for synthesizing data, and report results selectively. Separate reviews about harms could address some of these problems, and we argue that conducting separate reviews of harms is a feasible alternative to current standards and practices. Systematic reviews of potential benefits could be organized around the use of interventions for specific health problems. Systematic reviews of potential harms could be broader, including more diverse study designs and including all people at risk of harms (who might use the same intervention to treat different health problems). Multiple reviews about benefits could refer to a single review of harms. This approach could improve the reliability, completeness, and efficiency of systematic reviews.
An interdisciplinary student-led multifaceted intervention addressing overuse of broad-spectrum antibiotics for patients with penicillin allergies
Authors: Banashefski Bryana , Henson Philip , David Navindra , Kok Hui Ting , Beerkens Frans J. , Shyu Margaret , Linker Anne S. , Tsega Surafel , Dunn Andrew , Fuller Risa
Published: April 2023

Background

Though 15% of hospitalized patients have a documented penicillin (PCN) allergy, fewer than 1% have an IgE-mediated reaction that necessitates avoidance of β-lactam antibiotics.

Objective

Our interdisciplinary team of medical and nursing students led and executed a two-pronged quality improvement intervention to reduce prescribing of non-β-lactam antibiotics (NBLs) for patients with reported PCN allergies. To the best of our knowledge, this is the first multidisciplinary student-led intervention aimed at educating providers on low-risk penicillin allergy and encouraging best antibiotic prescribing practices.

Design and participants

The intervention took place from June 2021 to February 2022. We developed and provided clinician education modules, including peer-to-peer information sharing and in-person small group discussions, as well as clinical decision support (CDS) strategies through the electronic medical record (EMR). The target population was attendings, residents, nurse practitioners, and physician assistants on the hospital medicine service at a large urban academic tertiary care center. We followed the SQUIRE 2.0 guidelines for reporting on quality improvement.

Main measures

Primary outcome measures included number of NBL prescriptions and use of nonspecific descriptors (e.g., “other” or “unknown”) for PCN allergy reaction type, and were compared with a pre-intervention period.

Key results

The percent of β-lactam prescriptions for patients with a PCN allergy after the intervention increased from 19 to 23% (p = 0.006). For patients with a low severity PCN allergy, the percent of β-lactam prescriptions increased from 20 to 28% (p = 0.001). There was a significant decrease in nonspecific PCN allergy reaction type from 23% in the pre-intervention period to 20% post-intervention (p = 0.012).

Conclusions

An intervention focused on educating prescribers and CDS strategies delivered through the EMR increased appropriate β-lactam prescribing for patients with a documented low-risk PCN allergy and reduced the use of nonspecific PCN allergy reaction type in EMR documentation.
Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications
Authors: Tang Jinxin , Zhang Jinhui , Lu Yu , He Jieyu , Wang Hua , Liu Binfeng , Tu Chao , Li Zhihong
Published: April 2023

N6-methyladenosine (m6A) is considered as the most common and important internal transcript modification in several diseases like type 2 diabetes, schizophrenia and especially cancer. As a main target of m6A methylation, long non-coding RNAs (lncRNAs) have been proved to regulate cellular processes at various levels, including epigenetic modification, transcriptional, post-transcriptional, translational and post-translational regulation. Recently, accumulating evidence suggests that m6A-modified lncRNAs greatly participate in the tumorigenesis of cancers. In this review, we systematically summarized the biogenesis of m6A-modified lncRNAs and the identified m6A-lncRNAs in a variety of cancers, as well as their potential diagnostic and therapeutic applications as biomarkers and therapeutic targets, hoping to shed light on the novel strategies for cancer treatment.
Effect of Er,Cr:YSGG laser with a side-firing tip on decontamination of titanium disc surface: an in vitro and in vivo study
Authors: Kottmann Lucia , Franzen Rene , Conrads Georg , Wolfart Stefan , Marotti Juliana
Published: April 2023

Purpose

To evaluate the effectiveness of an erbium, chromium:yttrium–scandium–gallium–garnet (Er,Cr:YSGG) laser with side-firing tip in decontamination of titanium (Ti) disc.

Methods

In the first test series, 29 Ti-discs were contaminated with Staphylococcus aureus and treated as follows: positive control (no treatment); Perioflow; Laser A (0.75 W, 100 Hz), Laser B (1.5 W, 30 Hz); Laser C (no radiation, 60% water); and Laser D (no radiation, 50% water). For bacterial quantification, colony forming units (CFU, vital cells only) and quantitative PCR (qPCR, vital and devital cells) were performed. In a second test series, 92 Ti-discs were used, contaminated with in vivo-grown biofilm and treated as follows: positive control (no treatment); Perioflow; Laser E (1.5 W, 30 Hz), and Laser F (no radiation, 50% water). Considering the different and unknown culture conditions, quantification of bacteria was performed by broad-spectrum bacterial qPCR only. Based on the assumption that all cells of an organism contain an equivalent complement of genetic information, genome equivalent (GE) determination ensured the detection of the different intact and semi-intact genomes, regardless of type of bacterial species and vitality, circumvent the inherent bias of cultures.

Results

The GE values were significantly reduced by all interventions in both test series, compared to the positive control group (p < 0.001). In the first test series with S. aureus as model organism, Perioflow yielded a lower GE than the Laser groups A–D (all p < 0.025). The number of CFUs was significantly reduced in the intervention groups compared to the positive control (p < 0.001), except for Laser A (p = 0.157) and Laser D (p = 0.393). In the second test series, none of the pairwise comparisons of the intervention conditions showed a significant difference (Perioflow vs. Laser E: p = 0.732; Perioflow vs. Laser F: p = 0.590; Laser E vs. Laser F: p = 0.379).

Conclusion

The Er,Cr:YSGG laser with side-firing tip and Perioflow were equally capable of effectively decontaminating a Ti-disc surface. It is assumed that the bacterial reduction was largely due to the mechanical effect of the air and water stream.

Graphical Abstract
Recommendations for progression criteria during external randomised pilot trial design, conduct, analysis and reporting
Authors: Mellor Katie , Albury Charlotte , Dutton Susan J , Eldridge Sandra , Hopewell Sally
Published: April 2023

Background

External randomised pilot trials aim to assess whether a future definitive Randomised Controlled Trial (RCT) is feasible. Prespecified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive RCT should be conducted. This commentary presents a set of proposed recommendations for progression criteria to guide researchers when (i) designing, (ii) conducting, (iii) analysing and (iv) reporting external randomised pilot trials.

Methods

Recommendations were developed following a mixed methods approach. This involved (i) a methodological review of pilot trial publications, (ii) a cross-sectional study of pilot trial research funding applications, (iii) qualitative interviews with pilot trial researchers and (iv) a survey of corresponding authors of identified pilot trial publications. Initial recommendations were refined following two consultation stakeholder workshops held in July 2022.

Recommendations for progression criteria for external randomised pilot trials:

i. Design: consider progression criteria from the earliest opportunity; map progression criteria to feasibility objectives; consider quantitative and qualitative interpretations of feasibility; provide justification; develop guidelines rather than rules; seek input from relevant stakeholders.

ii. Conduct: regularly monitor pilot trial data against progression criteria.

iii. Analysis: avoid considering each progression criterion in isolation; engage in discussion with relevant stakeholders; consider context and other factors external to the pilot trial; consider feasibility (can we?) and progression (will we?).

iv. Reporting: we propose a reporting checklist in relation to progression criteria and recommend reporting in a table format for clarity.

Conclusion

These recommendations provide a helpful resource for researchers to consider progression criteria at different stages of external randomised pilot trials. We have produced a simple infographic tool to summarise these recommendations for researchers to refer to. Further research is needed to evaluate whether these proposed recommendations should inform future development, or update, of established guidelines for the design, conduct, analysis and reporting of external randomised pilot trials.
Neutrophil-inspired photothermo-responsive drug delivery system for targeted treatment of bacterial infection and endotoxins neutralization
Authors: Li Chengnan , Gan Yingying , Li Zongshao , Fu Mengjing , Li Yuzhen , Peng Xinran , Yang Yongqiang , Tian Guo-bao , Yang Yi Yan , Yuan Peiyan , Ding Xin
Published: April 2023

Background

P. aeruginosa
, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported.

Methods

A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A
P. aeruginosa
-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF.

Results

Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against
P. aeruginosa
(~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The
P. aeruginosa
murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF.

Conclusion

The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.
High blood pressure and associated factors among HIV-infected young persons aged 13 to 25 years at selected health facilities in Rwenzori region, western Uganda, September–October 2021
Authors: Migisha Richard , Ario Alex Riolexus , Kadobera Daniel , Bulage Lilian , Katana Elizabeth , Ndyabakira Alex , Elyanu Peter , Kalamya Julius N. , Harris Julie R.
Published: April 2023

Background

High blood pressure (HBP), including hypertension (HTN), is a predictor of cardiovascular events, and is an emerging challenge in young persons. The risk of cardiovascular events may be further amplified among people living with HIV (PLHIV). We determined the prevalence of HBP and associated factors among PLHIV aged 13 to 25 years in Rwenzori region, western Uganda.

Methods

We conducted a cross-sectional study among PLHIV aged 13 to 25 years at nine health facilities in Kabarole and Kasese districts during September 16 to October 15, 2021. We reviewed medical records to obtain clinical and demographic data. At a single clinic visit, we measured and classified BP as normal (< 120/ < 80 mmHg), elevated (120/ < 80 to 129/ < 80), stage 1 HTN (130/80 to 139/89), and stage 2 HTN (≥ 140/90). We categorized participants as having HBP if they had elevated BP or HTN. We performed multivariable analysis using modified Poisson regression to identify factors associated with HBP.

Results

Of the 1,045 PLHIV, most (68%) were female and the mean age was 20 (3.8) years. The prevalence of HBP was 49% (n = 515; 95% confidence interval [CI], 46%–52%), the prevalence of elevated BP was 22% (n = 229; 95% CI, 26%–31%), and the prevalence of HTN was 27% (n = 286; 95% CI, 25%–30%), including 220 (21%) with stage 1 HTN and 66 (6%) with stage 2 HTN. Older age (adjusted prevalence ratio [aPR], 1.21; 95% CI, 1.01–1.44 for age group of 18–25 years vs. 13–17 years), history of tobacco smoking (aPR, 1.41; 95% CI, 1.08–1.83), and higher resting heart rate (aPR, 1.15; 95% CI, 1.01–1.32 for > 76 beats/min vs. ≤ 76 beats/min) were associated with HBP.

Conclusions

Nearly half of the PLHIV evaluated had HBP, and one-quarter had HTN. These findings highlight a previously unknown high burden of HBP in this setting’s young populations. HBP was associated with older age, elevated resting heart rate, and ever smoking; all of which are known traditional risk factors for HBP in HIV-negative persons. To prevent future cardiovascular disease epidemics among PLHIV, there is a need to integrate HBP/HIV management.
Comparative evaluation of temperate, subtropical, and tropical isolates of nucleopolyhedrovirus against tomato fruit borer, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae)
Authors: Manzoor Saika , Gani Mudasir , Hassan Taskeena , Shafi Insha , Wani Fehim Jeelani , Mumtaz Shabnum , Eroglu Gozde Busra , Yaqoob Munazah , Mantoo Mohd Ayoob
Published: April 2023

Background

The tomato fruit borer, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae), is a serious insect pest owing to its polyphagous nature, migrating long distances, greater capacity to develop resistance against insecticides and persistence in cropping areas. The comparative evaluation of temperate, sub-tropical and tropical H. armigera NPV (HearNPV) isolates was carried out to determine the potential of local and exotic HearNPV isolates for the management of H. armigera in Kashmir, India, having a temperate climate.

Results

Mortality of 2nd instar H. armigera larvae with three different HearNPV isolates at different concentrations ranged between 13.40 and 73.25%, with significant differences between the concentrations in each isolate under laboratory conditions. The median lethal concentration (LC50) values of HearNPV-IND-K, HearNPV-IND-J, and HearNPV-IND-B isolates against 2nd instar H. armigera larvae were 4.62 × 103, 5.99 × 104, and 7.24 × 104 OBs/larva at 10th day post inoculation, with significant differences among the isolates. In time response bioassays, the cumulative mortality (%) caused by median lethal concentration (LC50) of HearNPV-IND-K, HearNPV-IND-J and HearNPV-IND-B isolates over a period of 10 days was 50.33, 49.00 and 49.00%, respectively. Their median survival time (ST50) values against 2nd instar H. armigera larvae were 8.10, 8.94 and 9.50 days, respectively, with significant differences among the isolates. The results revealed that the LC50 and ST50 values of HearNPV-IND K isolate were significantly lower than HearNPV-IND-J and HearNPV-IND-B isolates. The cumulative mortality of H. armigera larvae with HearNPV-IND-K, HearNPV-IND-J and HearNPV-IND-B isolates at different concentrations ranged between 22.00–68.32, 20.54–55.17, 11.66–44.33%, respectively, on tomato crop under field conditions. The highest mortality rate of 68.32% was observed at the local isolate (HearNPV-IND-K).

Conclusions

It’s concluded that the local isolate had the potential for the development of species-specific and environmentally safe biocontrol agent for organic farming and its incorporation into Integrated Pest Management program may reduce the use of chemical insecticides in Kashmir.
Mondor’s disease of the breast in Asia: a forgotten diagnosis for the front-line clinicians—a case report and literature review
Authors: Vijayan Pavitra , Pang Fui Tin
Published: April 2023

Background

Mondor’s disease is a rare, however, benign and self-limiting condition which can occur in the breast. Diagnosis of Mondor’s disease of the breast is not frequently made as this may be due the lack of awareness on this condition. Although majority of the documented cases were described to be idiopathic, it is wise to properly investigate for other causes such as hypercoagulability or an underlying malignancy. Only nine available case reports pertaining Mondor’s disease of the breast in Asia since 2011 were identified and reviewed.

Main body of abstract

We present a case of a 47-year-old, Malaysian, Malay, female who presented with a right breast swelling which was referred to the Radiology Department to rule out breast abscess. However, further clinical examination and radiological assessment proved it to be superficial thrombophlebitis of the lateral thoracic vein along the upper outer quadrant of her right breast. This condition was attributed to hypercoagulable state secondary to her newly diagnosed diabetes mellitus. After strict diabetic control, short course of antibiotics and symptomatic treatment, complete resolution of signs and symptoms were noted during her follow-up 6 weeks later.

Short conclusion

Mondor’s disease of the breast is believed to be more common than reported as many patients and even clinicians may not pay close attention to this complaint due to the mild symptoms of pain and its self-limiting nature. Raising awareness of the disease through this case review will broaden the scope of differential diagnosis for front-line clinicians when approaching patients presenting with a breast lump.
Experience With the Routine Use of Electronic Patient-Reported Outcome Measures for Patients With Lung Cancer
Authors: Crockett Cathryn , Price James , Pham Mai , Abdulwahid Danya , Bayman Neil , Blackhall Fiona , Bostock Layla , Califano Raffaele , Chan Clara , Coote Joanna , Cove-Smith Laura , Eaton Marie , Fenemore Jacqueline , Gomes Fabio , Harris Margaret , Halkyard Emma , Hughes Sarah , Lindsay Colin , Neal Hilary , McEntee Delyth , Pemberton Laura , Sheikh Hamid , Summers Yvonne , Taylor Paul , Woolf David , Yorke Janelle , Faivre-Finn Corinne
Published: April 2023

PURPOSE

The Christie NHS Foundation Trust launched their electronic patient-reported outcome measures (ePROMs) service in January 2019 in the routine clinical setting. The lung cancer questionnaires consist of 14 symptom items, adapted from the Common Terminology Criteria for Adverse Events (version 5.0) and the EuroQol EQ-5D-5L quality-of-life (QoL) tool. Patients with lung cancer are invited to complete questionnaires assessing their symptoms and QoL using an online platform.

METHODS

The ePROM responses and clinical, pathologic, and treatment data for patients who completed the questionnaires between January 2019 and December 2020 were extracted from electronic medical records. The symptom and QoL scores of patients who completed baseline pretreatment ePROMs and also those who completed ePROMs pre- and postpalliative lung systemic anticancer therapy (SACT) or radical thoracic radiotherapy were evaluated. Pretreatment questionnaires were analyzed according to age, Eastern Cooperative Oncology Group performance status (ECOG PS), and Adult Comorbidity Evaluation-27 (ACE-27) comorbidity score.

RESULTS

One thousand four hundred eighty patients with lung cancer were included. There were no statistically significant differences in symptoms and QoL scores between age groups. Cough ( P = .006) and EQ-5D-5L mobility scores ( P = .006) were significantly worse for patients with an ECOG PS of 0-1. Dyspnea ( P = .035), hemoptysis ( P = .023), nausea ( P = .041), mobility ( P = .004), and self-care ( P = .0420) were significantly worse for those with higher ACE-27 scores (2-3 v 0-1). Palliative SACT was associated with a significant improvement in cough ( P < .001) and hemoptysis ( P = .025), but significantly negatively affected mobility ( P = .013). Patients receiving radical thoracic radiotherapy reported a significant improvement in hemoptysis ( P = .042) but worse pain ( P = .002) and fatigue ( P = .01). Other changes in symptom and QoL scores were not significant.

CONCLUSION

The symptoms and QoL reported at baseline and before and after both palliative SACT and radical thoracic radiotherapy are clinically relevant and meaningful. We have demonstrated that routine implementation of ePROMs into clinical practice is feasible and can inform clinical practice and future research.