bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification and characterization of flowering genes in Citrus sinensis (L.) Osbeck: a comparison among C. Medica L., C. Reticulata Blanco, C. Grandis (L.) Osbeck and C. Clementina
Authors: Kaur Harleen , Manchanda Pooja , Sidhu Gurupkar S. , Chhuneja Parveen
Published: February 2024

Background

Flowering plays an important role in completing the reproductive cycle of plants and obtaining next generation of plants. In case of citrus, it may take more than a year to achieve progeny. Therefore, in order to fasten the breeding processes, the juvenility period needs to be reduced. The juvenility in plants is regulated by set of various flowering genes. The citrus fruit and leaves possess various medicinal properties and are subjected to intensive breeding programs to produce hybrids with improved quality traits. In order to break juvenility in Citrus, it is important to study the role of flowering genes. The present study involved identification of genes regulating flowering in Citrus sinensis L. Osbeck via homology based approach. The structural and functional characterization of these genes would help in targeting genome editing techniques to induce mutations in these genes for producing desirable results.

Results

A total of 43 genes were identified which were located on all the 9 chromosomes of citrus. The in-silico analysis was performed to determine the genetic structure, conserved motifs, cis-regulatory elements (CREs) and phylogenetic relationship of the genes. A total of 10 CREs responsible for flowering were detected in 33 genes and 8 conserved motifs were identified in all the genes. The protein structure, protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to study the functioning of these genes which revealed the involvement of flowering proteins in circadian rhythm pathways. The gene ontology (GO) and gene function analysis was performed to functionally annotate the genes. The structure of the genes and proteins were also compared among other Citrus species to study the evolutionary relationship among them. The expression study revealed the expression of flowering genes in floral buds and ovaries. The qRT-PCR analysis revealed that the flowering genes were highly expressed in bud stage, fully grown flower and early stage of fruit development.

Conclusions

The findings suggested that the flowering genes were highly conserved in citrus species. The qRT-PCR analysis revealed the tissue specific expression of flowering genes (CsFT, CsCO, CsSOC, CsAP, CsSEP and CsLFY) which would help in easy detection and targeting of genes through various forward and reverse genetic approaches.
Forced eruption in impacted teeth: analysis of failed cases and outcome of re-operation
Authors: Kim Jaeyeon , Jung Seoyeon , Lee Kee-Joon , Yu Hyung-Seog , Park Wonse
Published: February 2024

Background

Forced eruption of an impacted tooth usually requires surgical and orthodontic interventions to successfully bring the tooth into the dental arch. The clinical time required for a forced eruption is difficult to predict before treatment begins and success rates are affected by several factors before and after an eruption. This study was conducted to identify factors that affect the success of forced eruption, the duration of orthodontic treatment of impacted teeth, and the reasons for re-operation and forced eruption failure in a various teeth and cases.

Methods

In this retrospective study, the records regarding the forced eruption of 468 teeth in 371 patients from June 2006 to May 2020 at the Advanced General Dentistry Department of Yonsei University Dental Hospital were initially examined. The records of 214 teeth in 178 patients who completed orthodontic treatment were included in the analysis. Data on patient demographics, tooth characteristics, orthodontic treatment duration, re-operations, and failures were collected from electronic medical records.

Results

There was a significant difference in age between the success and failure forced eruption. Factors significantly affecting treatment duration were apex formation, position, rotation, and re-operation. Re-operation had a 96% success rate. The average orthodontic treatment duration was 29.99 ± 16.93 months, but the average orthodontic treatment duration for teeth that undergone re-operation was 20.36 ± 11.05 months, which was approximately 9 months shorter. Additionally, there was an interaction effect between rotation and re-operation on the duration of orthodontic treatment. The causes for failure of forced eruption in 6 cases were ankyloses (3 cases), incomplete alignment with the normal dental arch (2 cases), and a significant deviation in the impacted tooth’s location (1 case).

Conclusions

To increase the success rate of forced eruption, age should be considered as a priority, and in order to predict the treatment period, the apex formation status, position in the arch, and rotation should be considered in addition to age. When determining re-operation, considering factors such as ankylosis, root curvature, and apex formation can help in the success of orthodontic treatment.
Evaluation of whether there is residual polyp tissue after hysteroscopic morcellation at Cam and Sakura City Hospital: a retrospective cohort study
Authors: Sivas Mustafa Can , Ohanoglu Cetinel Karolin , Arslan Hilal Serap
Published: February 2024

Background

In polypectomy with mechanical hysteroscopic morcellators, the tissue removal procedure continues until no polyp tissue remains. The decision that the polypoid tissues were removed completely is made based on visual evaluation. In a situation where the polyp tissue was visually completely removed and no doubt that the polyp has been completely removed, short spindle-like tissue fragments on the polyp floor continue in most patients. There are no studies in the literature on whether visual evaluation provides adequate information at the cellular level in many patients in whom polypoid tissues have been determined to be completely removed. The aim of the present study was to analyze the pathological results of the curettage procedure, which was applied following the completion of polyp removal with operative hysteroscopy, and to evaluate whether there was residual polyp tissue in the short spindle-like tissue fragments that the mechanical hysteroscopic morcellator could not remove. The secondary aims of this study were to compare conventional loop resection hysteroscopy with hysteroscopic morcellation for the removal of endometrial polyps in terms of hemoglobin/hematocrit changes, polypectomy time and the amount of medium deficit.

Methods

A total of 70 patients with a single pedunculate polypoid image of 1.5-2 cm, which was primarily visualized by office hysteroscopy, were included in the study. Patients who had undergone hysteroscopic polypectomy were divided into two groups according to the surgical device used: the morcellator group (n = 35, Group M) and the resectoscope group (n = 35, Group R). The histopathological results of hysteroscopic specimens and curettage materials of patients who had undergone curettage at the end of operative hysteroscopy were evaluated. In addition, the postoperative 24th hour Hb/HCT decrease amounts in percentage, the polypectomy time which was measured from the start of morcellation, and deficit differences were compared between groups.

Results

In total, 7 patients in the morcellator group had residual polyp tissue detected in the full curettage material. The blood loss was lower in the morcellator group than in the resectoscope group (M, R; (-0.07 ± 0.08), (-0,11 ± 0.06), (p < 0.05), respectively). The deficit value of the morcellator group were higher (M, R; (500 ml), (300 ml), (p < 0.05), respectively). The polypectomy time was shorter in the morcellator group (M, R; mean (2.30 min), (4.6 min), (p < 0.05)).

Conclusions

Even if the lesion is completely visibly removed during hysteroscopic morcellation, extra caution should be taken regarding the possibility of residual tissue. There is a need for new studies investigating the presence of residual polyp tissue.
Cross-sectional analysis of financial relationships between board certified allergists and the pharmaceutical industry in Japan
Authors: Murayama Anju , Senoo Yuki
Published: February 2024

Background

Financial interactions between pharmaceutical companies and physicians lead to conflicts of interest. This study examines the extent and trends of non-research payments made by pharmaceutical companies to board-certified allergists in Japan between 2016 and 2020.

Methods

A retrospective analysis of disclosed payment data from pharmaceutical companies affiliated with the Japanese Pharmaceutical Manufacturers Association was conducted. The study focused on non-research payments for lecturing, consulting, and manuscript drafting made to board-certified allergists from 2016 to 2020. We performed descriptive analyses on payment data. Trends were analyzed using generalized estimating equation models.

Results

Of the 3,943 board-certified allergists, 2,398 (60.8%) received non-research payments totaling $43.4 million over five years. Lecturing fees comprised 85.7% ($37.2 million) of the total payment amounts. For allergists who received at least one payment, the median amount per allergist was $3,106 (interquartile range: $966 – $12,124), in contrast to a mean of $18,092 (standard deviation: $49,233) over the five-year span. The top 1% and 10% of these allergists accounted for 20.8% and 68.8% of all non-research payments, respectively. The annual payment amounts significantly increased by 7.2% annual increase (95% CI: 4.4 – 10.0%, p < 0.001) each year until 2019, but saw a significant decrease in 2020 amid the COVID-19 pandemic.

Conclusion

The majority of allergists received non-research payments, with a notable concentration among a small group. Payments increased annually until the pandemic’s onset, which coincided with a substantial decrease. Further research is needed to explore the implications of these financial interactions on clinical practice and patient care in Japan.
Levels and predictors of empathy, self-awareness, and perceived stress among nursing students: a cross sectional study
Authors: Hamaideh Shaher H. , Abuhammad Sawsan , Khait Abdallah Abu , Al-Modallal Hanan , Hamdan-Mansour Ayman M , Masa’deh Rami , Alrjoub Saleem
Published: February 2024

Background

High levels of empathy and self-awareness and low level of stress among nursing students are the core elements of improving patients’ care and outcomes. The purpose of this study is to assess the levels, relationships, and predictors of empathy, self-awareness, and perceived stress in a sample of undergraduate Jordanian nursing students.

Methods

A descriptive cross-sectional design was employed to collect data from 330 students using a web-based survey.

Results

The total mean scores of empathy, self-awareness, and perceived stress were 75.75, 40.17, and 55.65, respectively. Students who are studying in public universities, with higher GPA, who have no intention to leave nursing, and who are satisfied with nursing; reported higher level of empathy. Students with lower income level, who have no intention to leave nursing, and who are satisfied with nursing; reported higher level of self-awareness. Female students, those who sleeping 6 h and less, did not get a balanced diet or perform exercise, studying in public universities, lower GPA, have intention to leave nursing, and did not satisfy with nursing; reported higher level of perceived stress.

Conclusions

Nursing students reported adequate empathy level, low self-awareness level, and moderate perceived stress level. Students who are satisfied and have no intention to leave nursing reported higher level of empathy, self-awareness, and perceived stress. It is necessary to conduct interventional programs that enhance students’ well-being especially empathy and self-awareness, and reduce the level of their stress.
Changes in plasma PLAC-1 concentration and its expression during early-mid pregnancy in bovine placental tissues – a pilot study
Authors: Jamioł Monika , Sozoniuk Magdalena , Wawrzykowski Jacek , Kankofer Marta
Published: February 2024

Background

Placenta-specific protein 1 (PLAC1) is a small secreted protein considered to be a molecule with a significant role in the development of the placenta and the establishment of the mother-foetus interface. This study aimed to confirm the presence of bovine PLAC1 and to examine its profile in the placenta and plasma in the first six months of pregnancy. The expression pattern of PLAC1 was analysed by RT-qPCR and Western Blotting. Quantitative evaluation was carried out using ELISA.

Results

PLAC1 concentrations in the plasma of pregnant cows were significantly higher (p < 0.05) than those obtained from non-pregnant animals. PLAC1 protein concentrations in the placental tissues of the foetal part were significantly (p < 0.05) higher than in the tissues of the maternal part of the placenta. PLAC1 transcripts were detected in both placental tissue samples and epithelial cell cultures.

Conclusions

In conclusion, the results of the present preliminary study suggest that PLAC1 is involved in the development of bovine placenta. The presence of this protein in the plasma of pregnant animals as early as the first month may make it a potential candidate as a pregnancy marker in cows. Further studies on exact mechanisms of action of PLAC1 in bovine placenta are necessary.
A multidisciplinary study on Clinostomum infections in Nile tilapia: micro-morphology, oxidative stress, immunology, and histopathology
Authors: Mahdy Olfat A. , Abdel-Maogood Sahar Z. , Abdelsalam Mohamed , Salem Mai A.
Published: February 2024

Yellow grub disease, caused by Clinostomum metacercaria, is an endemic zoonotic infection in freshwater fish, responsible for Halzoun syndrome transmitted through the consumption of raw infected fish. This study aimed to conduct a multidisciplinary investigation integrating detailed morphology, oxidative stress, immunology, and histopathology alteration to advance our understanding of Clinostomum infection. In this annual study, 400 Nile tilapia (Oreochromis niloticus) were collected from the Nile River at Al Bahr Al Aazam, Giza Governorate to assess Clinostomum infection prevalence. Of the examined fish, 160 individuals (40.0%) harboured larval Clinostomum infections. Clinostomum metacercariae were observed in various anatomical locations, with 135 fish (33.8%) in buccal cavities, 21 fish (5.25%) in gill chambers, and 4 fish (1.0%) on the skin. Infection intensity ranged from 2 to 12 cysts per fish, averaging 5 cysts, notably with skin infections characterized by a single cyst in each fish. Macroscopic encysted metacercariae were collected from buccal cavities, gills, and skin. Micro-morphology revealed distinct features in C. complanatum, including an elliptical oral sucker with collar-like rings and large sensory papilla-like structures, contrasting with the absence of these features in C. phalacrocoracis. Oxidative stress, assessed through malondialdehyde (MDA) and nitric oxide levels, revealed an elevation in MDA to 35.13 ± 6 nmol/g and nitric oxide to 25.80 ± 3.12 µmol/g in infected fish. In infected fish, MHC-I gene expression increased approximately 13-fold, MHC-II peaked at 19-fold, and IL-1β significantly upregulated by 17-fold, compared to control levels. Histopathology detailed associated lesions, such as cyst encapsulation and eosinophilic infiltration. Clinstomiasis and its impacts on fish hosts offer crucial insights to control this emerging fish-borne zoonotic disease, threatening wildlife, aquaculture, and human health.
Low frequency of SLC26A4 c.919-2A > G variant among patients with nonsyndromic hearing loss in Yunnan of Southwest China
Authors: Li Yan-Qiong , Ma Heng , Wang Qin-Yao , Liu De-Sheng , Wang Wei , Li Shi-Xin , Zuo Rong-Xia , Shen Tao , Zhu Bao-Sheng , Sa Ya-Lian
Published: February 2024

Background

Gene variants are responsible for more than half of hearing loss, particularly in nonsyndromic hearing loss (NSHL). The most common pathogenic variant in SLC26A4 gene found in East Asian populations is c.919-2A > G followed by c.2168A > G (p.H723R). This study was to evaluate their variant frequencies in patients with NSHL from special education schools in nine different areas of Southwest China’s Yunnan.

Methods

We performed molecular characterization by PCR-products directly Sanger sequencing of the SLC26A4 c.919-2AG and c.2168 A > G variants in 1167 patients with NSHL including 533 Han Chinese and 634 ethnic minorities.

Results

The SLC26A4 c.919-2A > G variant was discovered in 8 patients with a homozygous state (0.69%) and twenty-five heterozygous (2.14%) in 1167 patients with NSHL. The total carrier rate of the c.919-2A > G variant was found in Han Chinese patients with 4.50% and ethnic minority patients with 1.42%. A significant difference existed between the two groups (P < 0.05). The c.919-2A > G allele variant frequency was ranged from 3.93% in Kunming to zero in Lincang and Nvjiang areas of Yunnan. We further detected the SLC26A4 c.2168 A > G variant in this cohort with one homozygotes (0.09%) and seven heterozygotes (0.60%), which was detected in Baoshan, Honghe, Licang and Pu`er areas. Between Han Chinese group (0.94%) and ethnic minority group (0.47%), there was no statistical significance (P > 0.05). Three Han Chinese patients (0.26%) carried compound heterozygosity for c.919-2A > G and c.2168 A > G.

Conclusion

These data suggest that the variants in both SLC26A4 c.919-2A > G and c.2168 A > G were relatively less frequencies in this cohort compared to the average levels in most regions of China, as well as significantly lower than that in Han-Chinese patients. These results broadened Chinese population genetic information resources and provided more detailed information for regional genetic counselling for Yunnan.
Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study
Authors: Tu Junhao , Wen Jinyang , Luo Qing , Li Xin , Wang Deyun , Ye Jing
Published: February 2024

Background

Allergic diseases exert a considerable impact on global health, thus necessitating investigations into their etiology and pathophysiology for devising effective prevention and treatment strategies. This study employs a Mendelian randomization (MR) analysis and meta-analysis to identify metabolite targets potentially associated with allergic diseases.

Methods

A two-sample MR analysis was conducted to explore potential causal relationships between circulating and urinary metabolites and allergic diseases. Exposures were derived from a genome-wide association study (GWAS) of 486 circulating metabolites and a GWAS of 55 targeted urinary metabolites. Outcome data for allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, were obtained from the FinnGen biobank in Europe (cohort 1) and the Biobank Japan in Asia (cohort 2). MR results from both cohorts were combined using a meta-analysis.

Results

MR analysis identified 50 circulating metabolites and 6 urinary metabolites in cohort 1 and 54 circulating metabolites and 2 urinary metabolites in cohort 2 as potentially causally related to allergic diseases. A meta-analysis of the MR results revealed stearoylcarnitine (OR 8.654; 95% CI 4.399−17.025; P = 4.06E-10) and 1-arachidonoylglycerophosphoinositol (OR 2.178; 95% CI 1.388−3.419; P = 7.15E-04) as the most reliable causal circulating metabolites for asthma and AR, respectively. Further, histidine (OR 0.734; 95% CI: 0.594−0.907; P = 0.004), tyrosine (OR 0.601; 95% CI: 0.380−0.952; P = 0.030), and alanine (OR 0.280; 95% CI: 0.125−0.628; P = 0.002) emerged as urinary metabolites with the greatest protective effects against asthma, AD, and AR, respectively.

Conclusions

Imbalances in numerous circulating and urinary metabolites may be implicated in the development and progression of allergic diseases. These findings have significant implications for the development of targeted strategies for the prevention and treatment of allergic diseases.
Assessing the acceptability and feasibility of remote spirometric monitoring for rural patients with interstitial lung disease: a multimethod approach
Authors: Boente Ryan D. , Schacht Sydney , Borton Rebecca , Vincent Joseph , Golzarri-Arroyo Lilian , Rattray Nicholas
Published: February 2024

Introduction

Interstitial lung disease encompasses a group of rare lung conditions causing inflammation and scarring of lung tissue. The typical method of monitoring disease activity is through pulmonary function tests performed in a hospital setting. However, accessing care can be difficult for rural patients due to numerous barriers. This study assesses the feasibility and acceptability of home spirometry telemonitoring using MIR-Spirometers and the patientMpower home-monitoring platform for rural patients with interstitial lung disease.

Methods

Unblinded, uncontrolled, prospective, multiple-methods study of the feasibility and utility of remote monitoring of 20 rural subjects with interstitial lung disease. Study assessments include adherence to twice weekly spirometry for 3 months in addition to mMRC dyspnea and EQ-5D-5L health-related quality of life questionnaires with each spirometry maneuver. Upon completion, subjects were encouraged to complete an 11-question satisfaction survey and participate in semi-structured qualitative interviews to further explore expectations and perceptions of rural patients to telehealth and remote patient monitoring.

Results

19 subjects completed the 3-month study period. Adherence to twice weekly spirometry was mean 53% ± 38%, with participants on average performing 2.26 ± 1.69 maneuvers per week. The median (Range) number of maneuvers per week was 2.0 (0.0, 7.0). The majority of participants responded favorably to the patient satisfaction survey questions. Themes regarding barriers to access included: lack of local specialty care, distance to center with expertise, and time, distance, and high cost associated with travel. Remote monitoring was well perceived amongst subjects as a way to improve access and overcome barriers.

Conclusions

Remote spirometry monitoring through web-based telehealth is acceptable and feasible for rural patients. Perceived benefits include overcoming access barriers like time, distance, and travel costs. However, cost, reimbursement, and internet access must be addressed before implementing it widely. Future studies are needed to ensure long-term feasibility and to compare outcomes with usual care.
Association of dietary inflammatory index and the SARS-CoV-2 infection incidence, severity and mortality of COVID-19: a systematic review and dose-response meta-analysis
Authors: Hao Xuanyu , Li Shiwen , Yang Yanmin , Dai Huixu , Yan Yumeng , Li Dongyang
Published: February 2024

Background

Several studies have reported the association between dietary inflammatory index (DII) and the SARS-CoV-2 infection risk, severity or mortality of COVID-19, however, the outcomes remain controversial.

Objective

We sought to examine whether a dose-response association of DII and SARS-CoV-2 infection exists.

Design

A dose-response meta-analysis was performed to investigate the association of DII and SARS-CoV-2 infection. We conducted a systematic search of PubMed, Embase and Web of Science up to March 15th, 2023. The odds ratios (OR) of DII and COVID-19 risk and severity were computed.

Results

Totally, 5 studies were included (1 from UK and 4 from Iran), consisting of 197,929 participants with 12,081 COVID-19 cases. Although there was heterogeneity among studies, the results indicated that higher DII was independently related to higher SARS-CoV-2 infection incidence (OR = 1.57, 95% CI: 1.14, 2.17) and COVID-19 severity (OR = 1.11, 95% CI: 1.07, 1.15) but not COVID-19 mortality (risk ratio = 1.13, 95% CI: 1.00, 1.27). The incidence of SARS-CoV-2 infection increased by 31% for each 1-point increase in the E-DII (OR = 1.31, 95% CI: 1.20, 1.43).

Conclusions

This meta-analysis suggests that an elevated DII score is associated with increased SARS-CoV-2 infectious risk and severity of COVID-19. There were not enough studies on COVID-19 mortality. Further large prospective studies in different countries are warranted to validate our results.
Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide
Authors: Toulmonde Maud , Guegan Jean-Philippe , Spalato-Ceruso Mariella , Peyraud Florent , Kind Michèle , Vanhersecke Lucile , Le Loarer François , Perret Raul , Cantarel Coralie , Bellera Carine , Bessede Alban , Italiano Antoine
Published: February 2024

Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.

We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, ‘cold’ STS, characterized by an absence of tertiary lymphoid structures. The trial employed a two-stage Simon design. JX-594 was administered intratumorally at a dose of 1.109 pfu every 2 weeks for up to 4 intra-tumoral administrations. Cyclophosphamide was given orally at 50 mg twice daily in a week-on, week-off schedule, and avelumab was administered at 10 mg/kg biweekly. The primary endpoint was the 6-month non-progression rate.

Fifteen patients were enrolled, with the most frequent toxicities being grade 1 fatigue and fever. Fourteen patients were assessable for efficacy analysis. At 6 months, only one patient remained progression-free, indicating that the trial did not meet the first stage endpoint of Simon’s design. Analysis of sequential tissue biopsies and plasma samples revealed an increase in CD8 density and upregulation of immune-related protein biomarkers, including CXCL10.

Intra-tumoral administration of JX-594 in combination with cyclophosphamide and avelumab is safe and capable of modulating the TME in cold STS. However, the limited efficacy observed warrants further research to define the therapeutic potential of oncolytic viruses, particularly in relation to specific histological subtypes of STS.
Feeling safer: effectiveness, feasibility, and acceptability of continuous pulse oximetry for people who smoke opioids at overdose prevention services in British Columbia, Canada
Authors: Moe Jessica , Chavez Tamara , Marr Charotte , Cameron Fred , Feldman-Kiss Damian , Wang Yueqiao Elle , Xavier Jessica C. , Mamdani Zahra , Purssell Roy A. , Salmon Amy , Buxton Jane A.
Published: February 2024

Background

Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids.

Methods

This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers.

Results

We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using “down”, heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again.

Conclusions

Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS.
Psychometric evaluation of the respiratory syncytial virus infection, intensity and impact questionnaire (RSV-iiiQ) in adults
Authors: Williams Valerie , DeMuro Romano Carla , Finelli Lyn , Qin Shanshan , Saretsky Todd L. , Ma Jia , Lewis Sandy , Phillips Matthew , Osborne Richard H. , Norquist Josephine M.
Published: February 2024

Background

Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ.

Methods

Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed.

Results

111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory.

Conclusions

RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.
The role of provincial health administration in supporting district health management teams in the Democratic Republic of Congo: eliciting an initial programme theory of a realist evaluation
Authors: Bosongo Samuel , Belrhiti Zakaria , Chenge Faustin , Criel Bart , Coppieters Yves , Marchal Bruno
Published: February 2024

Background

In 2006, the Ministry of Health in the Democratic Republic of Congo designed a strategy to strengthen the health system by developing health districts. This strategy included a reform of the provincial health administration to provide effective technical support to district health management teams in terms of leadership and management. The provincial health teams were set up in 2014, but few studies have been done on how, for whom, and under what circumstances their support to the districts works. We report on the development of an initial programme theory that is the first step of a realist evaluation seeking to address this knowledge gap.

Methods

To inform the initial programme theory, we collected data through a scoping review of primary studies on leadership or management capacity building of district health managers in sub-Saharan Africa, a review of policy documents and interviews with the programme designers. We then conducted a two-step data analysis: first, identification of intervention features, context, actors, mechanisms and outcomes through thematic content analysis, and second, formulation of intervention–context–actor–mechanism–outcome (ICAMO) configurations using a retroductive approach.

Results

We identified six ICAMO configurations explaining how effective technical support (i.e. personalised, problem-solving centred and reflection-stimulating) may improve the competencies of the members of district health management teams by activating a series of mechanisms (including positive perceived relevance of the support, positive perceived credibility of provincial health administration staff, trust in provincial health administration staff, psychological safety, reflexivity, self-efficacy and perceived autonomy) under specific contextual conditions (including enabling learning environment, integration of vertical programmes, competent public health administration staff, optimal decision space, supportive work conditions, availability of resources and absence of negative political influences).

Conclusions

We identified initial ICAMO configurations that explain how provincial health administration technical support for district health management teams is expected to work, for whom and under what conditions. These ICAMO configurations will be tested in subsequent empirical studies.
Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis
Authors: Gao Peng , Wang Jianyou , Tang Huan , Pang Huanhuan , Liu Jiemei , Wang Chen , Xia Fei , Chen Honglin , Xu Liting , Zhang Junzhe , Yuan Lixia , Han Guang , Wang Jigang , Liu Gang
Published: February 2024

Background

Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive.

Methods

We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays.

Results

The results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects.

Conclusions

In conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel.
Arthroscopic wafer procedure versus ulnar shortening osteotomy for ulnar impaction syndrome: a systematic review and meta-analysis
Authors: Shi Haifeng , Huang Yongjing , Shen Yong , Wu Ke , Zhang Zhihai , Li Qian
Published: February 2024

Purpose

This study aimed to systematically compare the efficacy and safety of arthroscopic wafer procedure (AWP) versus ulnar shortening osteotomy (USO) for ulnar impaction syndrome (UIS) treatment.

Methods

All the studies included in this meta-analysis compared the efficacy of AWP to USO for UIS and were acquired through a comprehensive search across multiple databases. The meta-analysis was performed by calculating the effect sizes with the Cochrane Collaboration’s RevMan 5.4 software.

Results

A total of 8 articles were included in this analysis, comprising 148 cases in the AWP group and 163 cases in the USO group. The pooled estimates indicated no significant differences in combined Darrow’s Criteria or Modified Mayo Wrist Score, Modified Mayo Wrist Score, DASH scores, grip strength, VAS score, and postoperative ulnar variation. On the other hand, the patients in the AWP group exhibited fewer complications (OR = 0.17, 95%CI 0.05–0.54, P = 0.003) and a lower reoperation rate (OR = 0.12, 95%CI 0.05–0.28, P < 0.00001) than those in the USO group.

Conclusions

The two surgical techniques were both effective in treating UIS but the AWP group showed fewer complications and a lower reoperation rate. Therefore, AWP may present a superior alternative for UIS treatment.
Phenylketonuria from the perspectives of patients in Türkiye
Authors: Esgi Merve , Ergun Hakan , Kaya Nazmi Yalcin , Atakay Deniz Yilmaz , Erucar Ege , Celik Fatma
Published: February 2024

Background

The present study aimed to determine the problems, unmet needs and expectations of phenylketonuria (PKU) patients in Türkiye regarding follow-up and treatment in order to provide data for future planning and implementations on PKU.

Methods

The study included patients diagnosed with PKU and/or their parents. They were informed about the study via phone calls and their verbal consents were obtained. Questions in the data collection forms, which were established separately for pediatric, adolescent, and adult age groups, were applied during the interviews and the answers were recorded.

Results

Among 182 classical PKU patients, 66 (36.3%) were in the pediatric group (0–12 years old), 44 (24.2%) were in the adolescent group (13–19 years old), and 72 (39.5%) were in the adult group (≥ 20 years old). In all patient groups, phenylalanine-restricted diet and medical nutrition products were the main options for treatment. The median of the last measured blood phenylalanine concentration (patient-reported) was 290 µmol/L, 425 µmol/L, and 750 µmol/L in the pediatric, adolescent, and adult groups, respectively. The frequency of blood testing for serum phenylalanine level according to the age groups was appropriate in nearly half of the patients. While the majority of the patients have been visiting the metabolism center they have been diagnosed with PKU for control, considerable proportion of the patients would like to change the center or the doctor they visit for control if they could. It was determined that nearly half of the patients had trouble in accessing the metabolism center. Treatment options’ being limited and expensive were the major problems. The main requests of the patients and patient relatives included easier access to the metabolism centers and more options for treatment and diet.

Conclusions

Access to the services should be easier to improve the patients’ follow-up and treatment. There is need for low-cost, easily applicable, and accessible nutrition products and effective novel pharmacological agents. Focusing on these issues in health policies by providing pedagogic/psychological support, establishing support programs also comprising the families, and increasing the awareness activities were the key outcomes.
A bifactor representation of the Center for Epidemiological Studies Depression Scale for children: gender and age invariance and implications for adolescents’ social and academic adjustment
Authors: Zhao Yanhua , Niu Jiahui , Huang Jing , Meng Yan
Published: February 2024

Background

The Center for Epidemiological Studies Depression Scale for Children (CES-DC) is a widely used scale for screening depressive symptoms in children and adolescents. This study aims to uncover the optimal factor structure of the DES-DC and presents an alternate conceptualization of adolescent depression by estimating bifactor models and several competing models using a sample of Chinese adolescents.

Methods

The participants were 533 adolescents (49.7% boys, 49.7% girls, 3 participants did not report) between 12 and 18 years of age attending public secondary schools in the middle part of mainland China. Data were collected in classrooms using a questionnaire survey. A structural equation modeling approach was used to estimate and compare a series of competing models for the DES-DC.

Results

A Bifactor exploratory structural equation model (Bi-ESEM) with the best model fit was retained for representing the current data. Tests of measurement invariance demonstrated strict measurement equivalence across gender and age. No gender and age differences have been found in the general depression factor. Findings provided evidence for the composite reliability and construct validity of DES-DC. Depressive symptoms positively related to the Big Five trait neuroticism, negative emotions, loneliness, social anxious behaviors, and disruptive behaviors during school and negatively related to agreeableness, conscientiousness, extraversion, physical health status, school connectedness, and academic self-efficacy.

Conclusions

This study provides support for the one general factor construct of the CES-DC and the continuum concept structure of adolescent depression. Moreover, this research offers empirical evidence for comparing depression symptoms among adolescent populations with diverse genders and age groups. Additionally, the findings replicate and expand upon the implications of depressive symptoms on adolescents’ traits, well-being, social-relational adjustment, and academic adaptation.
The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I&T for triple-negative breast cancer
Authors: Heesch Amelie , Florea Alexandru , Maurer Jochen , Habib Pardes , Werth Laura S. , Hansen Thomas , Stickeler Elmar , Sahnoun Sabri E. M. , Mottaghy Felix M. , Morgenroth Agnieszka
Published: February 2024

Introduction

Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC.

Methods

Rj:NMRI-Foxn1nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography.

Results

Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature.

Conclusion

This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC.

Graphical abstract
DNA satellite and chromatin organization at mouse centromeres and pericentromeres
Authors: Packiaraj Jenika , Thakur Jitendra
Published: February 2024

Background

Centromeres are essential for faithful chromosome segregation during mitosis and meiosis. However, the organization of satellite DNA and chromatin at mouse centromeres and pericentromeres is poorly understood due to the challenges of assembling repetitive genomic regions.

Results

Using recently available PacBio long-read sequencing data from the C57BL/6 strain, we find that contrary to the previous reports of their homogeneous nature, both centromeric minor satellites and pericentromeric major satellites exhibit a high degree of variation in sequence and organization within and between arrays. While most arrays are continuous, a significant fraction is interspersed with non-satellite sequences, including transposable elements. Using chromatin immunoprecipitation sequencing (ChIP-seq), we find that the occupancy of CENP-A and H3K9me3 chromatin at centromeric and pericentric regions, respectively, is associated with increased sequence enrichment and homogeneity at these regions. The transposable elements at centromeric regions are not part of functional centromeres as they lack significant CENP-A enrichment. Furthermore, both CENP-A and H3K9me3 nucleosomes occupy minor and major satellites spanning centromeric-pericentric junctions and a low yet significant amount of CENP-A spreads locally at centromere junctions on both pericentric and telocentric sides. Finally, while H3K9me3 nucleosomes display a well-phased organization on major satellite arrays, CENP-A nucleosomes on minor satellite arrays are poorly phased. Interestingly, the homogeneous class of major satellites also phase CENP-A and H3K27me3 nucleosomes, indicating that the nucleosome phasing is an inherent property of homogeneous major satellites.

Conclusions

Our findings reveal that mouse centromeres and pericentromeres display a high diversity in satellite sequence, organization, and chromatin structure.
A mathematical model for evaluating the impact of nonpharmaceutical interventions on the early COVID-19 epidemic in the United Kingdom
Authors: Zhang Hongyu , Jing Shuanglin
Published: February 2024

The coronavirus disease 2019 (COVID-19) presents a severe and urgent threat to global health. In response to the COVID-19 pandemic, many countries have implemented nonpharmaceutical interventions (NPIs), including national workplace and school closures, personal protection, social distancing, contact tracing, testing, home quarantine, and isolation. To evaluate the effectiveness of these NPIs in mitigating the spread of early COVID-19 and predict the epidemic trend in the United Kingdom, we developed a compartmental model to mimic the transmission with time-varying transmission rate, contact rate, disease-induced mortality rate, proportion of quarantined close contacts, and hospitalization rate. The model was fitted to the number of confirmed new cases and daily number of deaths in five stages with a Markov Chain Monte Carlo method. We quantified the effectiveness of NPIs and found that if the transmission rate, contact rate, and hospitalization rate were approximately equal to those in the second stage of the most strict NPIs, and the proportion of quarantined close contacts increased by 3%, then the epidemic would die out as early as January 12, 2021, with around 1,533,000 final cumulative number of confirmed cases, and around 55,610 final cumulative number of deaths.