bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of sertraline in alleviating uremic pruritus in hemodialysis patients: a randomized clinical trial
Authors: Elsayed Mohamed Mamdouh , Elgohary Iman Ezzat , Abdelhamid Heidi Hesham Said , Zaki Sherif Aziz
Published: June 2023

Introduction

Uremic pruritus (UP) is a common and distressing symptom in end stage renal disease (ESRD) patients. Many approaches have been tested to improve UP without a clear success. We aimed to assess the effect of sertraline on UP in hemodialysis (HD) patients.

Methods

This research is a double-blinded, placebo-controlled, multicentric randomized clinical trial which included sixty patients maintained on regular HD. Patients were allocated to receive sertraline 50 mg twice daily or placebo for 8 weeks. The Visual analogue scale (VAS) and the 5-D itch scale were used to assess pruritus before and after the course of treatment.

Results

At study end in sertraline group, there was a significant decrease from baseline findings in the VAS score (p < 0.001), and the 5-D itch scale (p < 0.001). On the other hand, in placebo group the VAS score showed a slight non-significant decrease (p = 0.469), and the 5-D scale (p = 0.584) increased from baseline measurements. The percentage of patients with severe and very severe pruritus decreased significantly in the sertraline group in both scores [(VAS score: p = 0.004), (5-D itch score: p = 0.002)] with no significant change in the placebo group [(VAS score: p = 0.739), (5-D itch scale: p = 0.763)]. There was a significant positive relation between the VAS and 5-D itch scores and serum urea with p value of 0.002 and 0.001 respectively, and serum ferritin with p value of < 0.001 with both.

Conclusions

Patients treated with sertraline had a significant improvement in pruritus as compared with those who received placebo suggesting a potential role for sertraline to treat uremic pruritus in HD patients. Larger randomized clinical trials are needed to confirm these findings.

Trial registration

ClinicalTrials.gov NCT05341843. First registration date: 22/04/2022.
Associations of maternal pre-pregnancy BMI and gestational weight gain with the risks of adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus
Authors: Ke Jiang-Feng , Liu Sheng , Ge Ri-Le , Ma Li , Li Mei-Fang
Published: June 2023

Background

Give the high background risk of adverse pregnancy outcomes (APOs), it is important to understand the associations of maternal pre-pregnancy body mass index (ppBMI), gestational weight gain (GWG) with APOs in women with gestational diabetes mellitus (GDM). We addressed the independent and joint associations of maternal ppBMI and GWG with APOs in Chinese women with GDM.

Methods

764 GDM women with singleton delivery were studied and they were stratified into three weight groups by ppBMI (underweight, normal weight and overweight/obesity) following classification standards for Chinese adults and three GWG groups (inadequate, adequate, excessive GWG) by the 2009 Institute of Medicine guidelines, respectively. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios of APOs.

Results

Maternal overweight/obesity was associated with increased odds of pregnancy-induced hypertension [PIH, adjusted odds ratio (aOR): 2.828, 95% confidence interval (CI) 1.382–5.787], cesarean delivery (CS) (aOR 2.466, 95%CI 1.694–3.590), preterm delivery (aOR 2.466, 95%CI 1.233–4.854), LGA (aOR 1.664, 95%CI 1.120–2.472), macrosomia (aOR 2.682, 95%CI 1.511–4.760) and any pregnancy complication (aOR 2.766, 95%CI 1.840–4.158) compared with healthy weight. Inadequate GWG was less likely to develop PIH (aOR 0.215, 95%CI 0.055–0.835), CS (aOR 0.612, 95%CI 0.421–0.889) and any pregnancy complication (aOR 0.628, 95%CI 0.435–0.907), but had higher risk of preterm birth (aOR 2.261, 95%CI 1.089–4.692), while excessive GWG was more vulnerable to LGA (aOR 1.929, 95%CI 1.272–2.923), macrosomia (aOR 2.753, 95%CI 1.519–4.989) and any pregnancy complication (aOR 1.548, 95%CI 1.006–2.382) as compared to adequate GWG. Furthermore, compared to normal weight mothers with adequate GWG, obese mothers with excessive GWG had the highest risk of any pregnancy complication (aOR 3.064, 95%CI 1.636–5.739).

Conclusions

Maternal overweight/obesity and GWG were associated with APOs in the already high-risk settings of GDM. Obese mothers with excessive GWG may confer the greatest risk of adverse outcomes. It was very helpful to reduce the burden of APOs and benefit GDM women by promoting a healthy pre-pregnancy BMI and GWG.
Abdominal pregnancy secondary to uterine horn pregnancy: a case report
Authors: Zheng Xingju , Zhou Yao , Sun Zhucheng , Yan Ting , Yang Yan , Wang Rongpin
Published: June 2023

Background

Pregnancy begins with a fertilized ovum that normally attaches to the uterine endometrium. However, an ectopic pregnancy can occur when a fertilized egg implants and grows outside the uterine cavity. Tubal ectopic pregnancy is the most common type (over 95%), with ovarian, abdominal, cervical, broad ligament, and uterine cornual pregnancy being less common. As more cases of ectopic pregnancy are diagnosed and treated in the early stages, the survival rate and fertility retention significantly improve. However, complications of abdominal pregnancy can sometimes be life-threatening and have severe consequences.

Case presentation

We present a case of intraperitoneal ectopic pregnancy with fetal survival. Ultrasound and magnetic resonance imaging showed a right cornual pregnancy with a secondary abdominal pregnancy. In September 2021, we performed an emergency laparotomy, along with additional procedures such as transurethral ureteroscopy, double J-stent placement, abdominal fetal removal, placentectomy, repair of the right uterine horn, and pelvic adhesiolysis, in the 29th week of pregnancy. During laparotomy, we diagnosed abdominal pregnancy secondary to a rudimentary uterine horn. The mother and her baby were discharged eight days and 41 days, respectively, after surgery.

Conclusions

Abdominal pregnancy is a rare condition. The variable nature of ectopic pregnancy can cause delays in timely diagnosis, resulting in increased morbidity and mortality, especially in areas with inadequate medical and social services. A high index of suspicion, coupled with appropriate imaging studies, can help facilitate its diagnosis in any suspected case.
The pretherapeutic systemic inflammation score is a prognostic predictor for elderly patients with oesophageal cancer: a case control study
Authors: Huang Chunyue , Wang Mengyao , Chen Liwen , Wang Hongmei , Huang Donglan , Shi Jianjun , Zhang Weijun , Tian Yunhong , Zhu Yujia
Published: June 2023

Background

The systemic inflammation score (SIS), based on serum albumin (Alb) and lymphocyte-to-monocyte ratio (LMR), is a novel prognostic tool for some tumours. Studies indicate that the SIS can be used as a postoperative prognostic marker. However, its predictive value in elderly oesophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is unclear.

Methods

In total, 166 elderly ESCC patients who received radiotherapy with or without chemotherapy were included. Based on different combinations of Alb and LMR levels, the SIS was divided into 3 groups, SIS = 0 (n = 79), SIS = 1 (n = 71) and SIS = 2 (n = 16). The Kaplan—Meier method was used for survival analysis. Univariate and multivariate analyses were performed to assess prognosis. Time-dependent receiver operating characteristic (t-ROC) curves were used to compare the prognostic accuracy of the SIS with that of Alb, LMR, neutrophil-to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII).

Results

Decreased Alb and LMR were both associated with shorter OS, whereas a lower SIS was significantly associated with better outcomes. The OS of SIS = 0, SIS = 1 and SIS = 2 was 28.0 ± 2.9, 16.0 ± 2.8 and 10.0 ± 7.0 months, respectively (p = 0.000). Similar results were also observed for PFS. Multivariate analysis of the model with SIS revealed that the SIS was a significant independent biomarker for predicting OS and PFS. The nomogram showed that the C-index was improved to 0.677 when the SIS factor was incorporated. Furthermore, the 3-year OS rates for patients in the SIS-high group (SIS = 1 and SIS = 2) undergoing concurrent radiotherapy with a single agent (CCRT-1) and concurrent radiotherapy with two agents (CCRT-2) were 42% and 15%, respectively (p = 0.039). The t-ROC curve showed that the SIS was more sensitive than other prognostic factors for predicting overall survival.

Conclusion

The SIS may be a useful prognostic marker in elderly patients with ESCC receiving radiotherapy alone or chemoradiotherapy. The SIS showed a better predictive ability for OS than the continuous variable Alb and could stratify patient prognosis in different therapeutic regimens. CCRT-1 may be the best treatment for SIS-high patients.
Optimizing identification of consensus molecular subtypes in muscle-invasive bladder cancer: a comparison of two sequencing methods and gene sets using FFPE specimens
Authors: Koll Florestan J. , Döring Claudia , Olah Csilla , Szarvas Tibor , Köllermann Jens , Hoeh Benedikt , Chun Felix K.-H. , Reis Henning , Wild Peter J.
Published: June 2023

Background

Molecular subtypes predict prognosis in muscle-invasive bladder cancer (MIBC) and are explored as predictive markers. To provide a common base for molecular subtyping and facilitate clinical applications, a consensus classification has been developed. However, methods to determine consensus molecular subtypes require validation, particularly when FFPE specimens are used. Here, we aimed to evaluate two gene expression analysis methods on FFPE samples and to compare reduced gene sets to classify tumors into molecular subtypes.

Methods

RNA was isolated from FFPE blocks of 15 MIBC patients. Massive analysis of 3’ cDNA ends (MACE) and the HTG transcriptome panel (HTP) were used to retrieve gene expression. We used normalized, log2-transformed data to call consensus and TCGA subtypes with the consensusMIBC package for R using all available genes, a 68-gene panel (ESSEN1), and a 48-gene panel (ESSEN2).

Results

Fifteen MACE-samples and 14 HTP-samples were available for molecular subtyping. The 14 samples were classified as Ba/Sq in 7 (50%), LumP in 2 (14.3%), LumU in 1 (7.1%), LumNS in 1 (7.1%), stroma-rich in 2 (14.3%) and NE-like in 1 (7.1%) case based on MACE- or HTP-derived transcriptome data. Consensus subtypes were concordant in 71% (10/14) of cases when comparing MACE with HTP data. Four cases with aberrant subtypes had a stroma-rich molecular subtype with either method. The overlap of the molecular consensus subtypes with the reduced ESSEN1 and ESSEN2 panels were 86% and 100%, respectively, with HTP data and 86% with MACE data.

Conclusion

Determination of consensus molecular subtypes of MIBC from FFPE samples is feasible using various RNA sequencing methods. Inconsistent classification mainly involves the stroma-rich molecular subtype, which may be the consequence of sample heterogeneity with (stroma)-cell sampling bias and highlights the limitations of bulk RNA-based subclassification. Classification is still reliable when analysis is reduced to selected genes.
Psychotic-like experiences in non-clinical subgroups with and without specific beliefs
Authors: Hinterbuchinger B. , Koch M. , Trimmel M. , Litvan Z. , Baumgartner J. , Meyer E. L. , Friedrich F. , Mossaheb N.
Published: June 2023

Background

Assuming a transdiagnostic and extended psychosis phenotype, psychotic-like experiences (PLEs) and psychotic symptoms are on a phenomenological and temporal continuum between clinical and non-clinical populations. Recent research points towards differences in PLE proneness in different subgroups and clinical impact of different PLE subtypes. This study examines the prevalence of PLEs in three groups of individuals with and without specific sets of beliefs aiming to elucidate the question whether proneness to PLEs varies according to traditional versus less traditional supernatural beliefs.

Methods

The anonymized 16-item version of the Prodromal Questionnaire (PQ-16) was used to assess PLEs in three groups including individuals with religious beliefs (RB), belief in esoterism and paranormal phenomena (EB), and those embedded in scientific evidence approach and scepticism towards para-scientific theories (non-believers, NB). Male and female participants between 18 and 90 years were eligible for participation.

Results

The sample comprised 159 individuals including 41 RB individuals, 43 EB individuals, and 75 NB individuals. The mean PQ-16 score of the EB individuals (6.86 ± 4.13) was significantly higher compared to NB individuals (3.43 ± 2.99) and to RB individuals (3.38 ± 3.23) with almost twice the score (both p-values < 0.001). There was no significant difference between the PQ-16 scores of the NB group and the RB group (p = 0.935). No significant impact of age (p = 0.330) and gender (p = 0.061) was found on the PQ16-Score.

Group affiliation to esoterism was associated with a higher PQ-16 score compared to group affiliation to religious beliefs (p < 0.001) and group affiliation to scepticism (p = 0.011), while the latter two did not differ significantly (p = 0.735). No significant difference was found between the three groups in the degree of distress related to the affirmatively answered PQ-16 items (p = 0.74).

Conclusion

Under the assumption of a transdiagnostic psychosis phenotype, our findings provide more insight which subgroups within non-clinical samples have a higher likelihood of reporting PLEs.
The relationship between publication of high-quality evidence and changes in the volume and trend of subacromial decompression surgery for patients with subacromial pain syndrome in hospitals across Australia, Europe and the United States: a controlled interrupted time series analysis
Authors: Geurkink Timon H. , van Bodegom-Vos Leti , Nagels Jochem , Liew Susan , Stijnen Pieter , Nelissen Rob G.H.H. , Marang-van de Mheen Perla J.
Published: June 2023

Aims

To evaluate the extent to which publication of high-quality randomised controlled trials(RCTs) in 2018 was associated with a change in volume or trend of subacromial decompression(SAD) surgery in patients with subacromial pain syndrome(SAPS) treated in hospitals across various countries.

Methods

Routinely collected administrative data of the Global Health Data@work collaborative were used to identify SAPS patients who underwent SAD surgery in six hospitals from five countries (Australia, Belgium, Netherlands, United Kingdom, United States) between 01/2016 and 02/2020. Following a controlled interrupted time series design, segmented Poisson regression was used to compare trends in monthly SAD surgeries before(01/2016-01/2018) and after(02/2018-02/2020) publication of the RCTs. The control group consisted of musculoskeletal patients undergoing other procedures.

Results

A total of 3.046 SAD surgeries were performed among SAPS patients treated in five hospitals; one hospital did not perform any SAD surgeries. Overall, publication of trial results was associated with a significant reduction in the trend to use SAD surgery of 2% per month (Incidence rate ratio (IRR) 0.984[0.971–0.998]; P = 0.021), but with large variation between hospitals. No changes in the control group were observed. However, publication of trial results was also associated with a 2% monthly increased trend (IRR 1.019[1.004–1.034]; P = 0.014) towards other procedures performed in SAPS patients.

Conclusion

Publication of RCT results was associated with a significantly decreased trend in SAD surgery for SAPS patients, although large variation between participating hospitals existed and a possible shift in coding practices cannot be ruled out. This highlights the complexities of implementing recommendations to change routine clinical practice even if based on high-quality evidence.
Effects of the obstruction of erector spinae plane in affected people undergoing percutaneous vertebroplasty
Authors: Ju Peng , Jiang Dianming
Published: June 2023

Background

We aimed to compare the difference between the therapeutic effects of percutaneous vertebroplasty (PVP) as well as PVP combined with erector spinae plane blocked (ESPB) in osteoporotic vertebral compression fractures (OVCFs) therapy.

Methods

After the reception, 100 affected people to OVCFs were randomly divided into the PVP group as a control as well as the PVP + ESPB group as the observation, which included fifty affected people per group. The visual analog scale (VAS) for pain as well as the Oswestry Disability Index (ODI) per group was assessed before the operation, two hours after the operation, and when patients were discharged from the hospital. Operating time was also evaluated on the charged bulk of bone cement during the surgery, blood loss during the surgery, as well as operating costs for each group. Additionally, to assess differences, comparisons have been done among available groups in terms of ambulation as well as defecation or stool after the operation at the earlier time.

Results

The PVP + ESPB category acquired lower VAS and ODI scores when assessments were processed 2 h after the operation and when they were discharged from a hospital. They also had earlier postoperative ambulation and defecation time than the category of PVP (p < 0.05). Regarding the other indicators, there did not show significant differences. Besides, no complications occurred within both group, either after the operation or when they discharge from the hospital.

Conclusion

PVP + ESPB for OVCF is related to less VAS, further effective alleviation of pain, and fewer ODI values in affected people after the operation than only PVP. Besides, affected people can involve in ambulation more swiftly. The PVP + ESPB therapy improves the quicker recuperation of intestinal function as well as helps to improve the overall life quality of patients.
Salivary levels of five microorganisms of root caries in nursing home elderly: a preliminary investigation
Authors: Chen Lin , Qin Yuandong , Lin Yuhong , Du Minquan , Li Yuhong , Fan Mingwen
Published: June 2023

Background

Streptococcus, Bifidobacteria, Lactobacillus and Actinomyces are acidogenic aciduria that may be associated with root caries (RC). The aim of the study was to analyze Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), Bifidobacterium spp., Lactobacillus spp. and Actinomyces naeslundii (A. naeslundii) in the saliva of nursing home elderly, to assess the correlation between bacterial composition and RC for five putative catiogenic organisms.

Methods

In this study, we collected 43 saliva samples and divided into two groups: the root caries group (RCG, n = 21) and the caries-free group (CFG, n = 22). Bacterial DNA was extracted from the saliva samples. The presence and abundance of the five microorganisms were detected by Quantitative real-time PCR (qPCR). Spearman correlation test was performed to evaluate the relationship between the numbers of root decayed filled surfaces (RDFS) and root caries index (RCI) and salivary levels of the bacteria.

Results

The salivary levels of S. mutans, S. sobrinus, Bifidobacterium spp. and Lactobacillus spp. were significantly higher in RCG than in CFG (p < 0.05). RDFS and RCI (RDFS/RCI) were positively associated with salivary levels of S. mutans, S. sobrinus and Bifidobacterium spp. (r = 0.658/0.635, r = 0.465/0.420 and r = 0.407/0.406, respectively). No significant differences in presence and amounts of A. naeslundii was observed between the two groups (p > 0.05).

Conclusion

S. mutans, S. sobrinus and Bifidobacterium spp. in saliva appear to be associated with RC in the elderly. Taken together, the findings indicate that specific salivary bacteria may be involved in the progression of RC.
Improvement of oral health knowledge and behavior of diabetic patients: an interventional study using the social media
Authors: Haghdoost Atousa , Bakhshandeh Soheila , Tohidi Sajjad , Ghorbani Zahra , Namdari Mahshid
Published: June 2023

Background

Diabetic patients are not often aware of relationship between diabetes mellitus (DM) and periodontal diseases, and the researchers recommend further knowledge enhancement of diabetic patients in this regard. This study aimed to enhance oral health knowledge of diabetic adults via an educational intervention.

Methods

In this interventional study, three private offices of endocrinologists specialized in treatment of DM were selected for the recruitment of participants. In total, 120 diabetic adults (40 from each office) took part in an educational intervention in three groups (patients from each office made up one group): (I) physician-aid, (II) researcher-aid, and (III) social media. In group (I), participants received educational materials (brochure and CD) from their endocrinologist, in group (II) participants received educational materials from researcher. Group (III) joining an educational group in WhatsApp for 3 months. A self-reported standard questionnaire was filled out by the patients before, and after the intervention to assess oral health knowledge. Data were analyzed by SPSS version 21 using independent t-test, Mann-Whitney test, Chi-square test, and ANCOVA.

Results

The mean oral health knowledge score increased in all three groups after the educational interventions (P < 0.001); the highest increase occurred in the social media group. Toothbrushing twice daily or more had the greatest improvement in the physician-aid group compared with the other two groups (P < 0.001). The greatest improvement in dental flossing once daily or more occurred in the social media group (P = 0.01). The mean level of the hemoglobin A1c (HbA1c) decreased in all three groups, but not significantly (P = 0.83).

Conclusion

The results showed that educational interventions enhance oral health knowledge, and improve the behavior of diabetic adults. The education via the social media can be an efficient method for knowledge enhancement of diabetic patients.
Increased levels of PD1 and glycolysis in CD4+ T cells are positively associated with lymph node metastasis in OSCC
Authors: Wu Kun , Han Nannan , Mao Yuanyuan , Li Yan
Published: June 2023

Background

Cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC). Activated immune cells generally have metabolic abnormalities in the tumour microenvironment. However, it is unknown whether abnormal glycolysis in T cells could facilitate metastatic lymph nodes in OSCC patients. The aim of this study was to investigate the effects of immune checkpoints in metastatic lymph nodes and determine the correlation between glycolysis and immune checkpoint expression in CD4+ T cells.

Methods

Flow cytometry and immunofluorescence staining were used to analyse the differences in CD4+ PD1+ T cells between metastatic lymph nodes (LN+) and negative lymph nodes (LN−). RT‒PCR was performed to detail the expression of immune checkpoints and glycolysis-related enzymes in LN+ and LN−.

Results

The frequency of CD4+ T cells decreased in LN+ patients (p = 0.0019). The PD1 expression of LN+ increased markedly compared to that of LN− (p = 0.0205). Similarly, the PD1 of CD4+ T cells in LN+ increased significantly compared to that of LN−. Additionally, glycolysis-related enzyme levels in CD4+ T cells from LN+ patients were dramatically higher than those in LN− patients. PD1 and Hk2 expression in CD4+ T cells was also increased in LN+ OSCC patients with prior surgical treatment compared to those without.

Conclusions

These findings suggest that lymph node metastasis and recurrence in OSCC are associated with increases in PD1 and glycolysis in CD4+ T cells; this response may serve as a potential regulator of OSCC progression.
Prevalence and genotype screening of human papillomavirus among women attending a private hospital in Northern Cyprus: an 11-year retrospective study
Authors: Baddal Buket , Oktay Makbule Naz , Bostanci Aysegul , Yenen Mufit Cemal
Published: June 2023

Background

Human papillomavirus (HPV) is the most common sexually transmitted pathogen both in men and women. Accumulating epidemiological evidence supports a strong association between HPV infection and cancer of the cervix, vulva, vagina, anus, and penis. Currently, data on the HPV prevalence and genotyping is lacking in Northern Cyprus, a region in which HPV vaccination is not freely accessible via the national immunization program. The aim of this study was to evaluate the HPV type-specific prevalence in women with and without cytological abnormalities living in Northern Cyprus.

Methods

A total of 885 women who presented to the Department of Gynecology and Obstetrics Clinic between January 2011 and December 2022 were included in the study. Samples were collected for cytology. Cervical specimens were investigated for the presence of HPV-DNA and genotyping of HPV was performed using real-time polymerase chain reaction (rtPCR). Cytological examination was interpreted according to the Bethesda system.

Results

Among all patients, overall high-risk HPV DNA prevalence was 44.3%. HPV-16 and HPV-18 positivity was found in 10.4% and 3.7% of women respectively, while other high-risk HPV (OHR-HPV) was the most frequent type of HPV (30.2%). The highest frequency of HPV infection was observed in the 30–55 age group (51.0%), followed by the < 30 age group (45.7%). Co-infection with two or more HPV types was observed in 17.0% of all positive samples, in which the prevalence of HPV-16 + HPV-18 was 2.3%, HPV-16 + OHR-HPV and HPV-18 + OHR-HPV was 12.0% and 5.1%, respectively. Among the screened patients, 37.5% had abnormal and 62.5% had normal cytology results. HR-HPV positivity was 65.7% and 34.0% in patients with abnormal and normal cytology. The highest incidence of HRC-HPV was OHR-HPV types (44.7%) in positive cytology cases. Among women with a cytology result of ASCUS, L-SIL, H-SIL and unspecified dysplasia, 52.1%, 67.6%, 97.5% and 75.6% were respectively infected with HR-HPV.

Conclusion

The present study provides the latest epidemiological data related to HPV prevalence and genotype distribution among women living in Northern Cyprus. Considering the unavailability of free vaccination in the community, it is imperative to implement local HPV screening programs and provide guidelines on HPV prevention and measures during early school education.
SDG indicator 3.b.3 – an analysis of its robustness and challenges for measuring access to medicines for children
Authors: Joosse I. R. , Wirtz V. J. , van Mourik A. T. , Wagner B. A. , Mantel-Teeuwisse A. K. , Suleman F. , van den Ham H. A.
Published: June 2023

Background

Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines’ accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses.

Methods

Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared.

Results

The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0–58.8%) and 76.3% (range 57.2–90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range.

Conclusion

This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.
Clinical isolates of uncomplicated falciparum malaria from high and low malaria transmission areas show distinct pfcrt and pfmdr1 polymorphisms in western Ethiopia
Authors: Tadele Geletta , Jawara Aminata , Oboh Mary , Oriero Eniyou , Dugassa Sisay , Amambua-Ngwa Alfred , Golassa Lemu
Published: June 2023

Background

Pfcrt gene has been associated with chloroquine resistance and the pfmdr1 gene can alter malaria parasite susceptibility to lumefantrine, mefloquine, and chloroquine. In the absence of chloroquine (CQ) and extensive use of artemether–lumefantrine (AL) from 2004 to 2020 to treat uncomplicated falciparum malaria, pfcrt haplotype, and pfmdr1 single nucleotide polymorphisms (SNPs) were determined in two sites of West Ethiopia with a gradient of malaria transmission.

Methods

230 microscopically confirmed P. falciparum isolates were collected from Assosa (high transmission area) and Gida Ayana (low transmission area) sites, of which 225 of them tested positive by PCR. High-Resolution Melting Assay (HRM) was used to determine the prevalence of pfcrt haplotypes and pfmdr1 SNPs. Furthermore, the pfmdr1 gene copy number (CNV) was determined using real-time PCR. A P-value of less or equal to 0.05 was considered significant.

Results

Of the 225 samples, 95.5%, 94.4%, 86.7%, 91.1%, and 94.2% were successfully genotyped with HRM for pfcrt haplotype, pfmdr1-86, pfmdr1-184, pfmdr1-1042 and pfmdr1-1246, respectively. The mutant pfcrt haplotypes were detected among 33.5% (52/155) and 80% (48/60) of isolates collected from the Assosa and Gida Ayana sites, respectively. Plasmodium falciparum with chloroquine-resistant haplotypes was more prevalent in the Gida Ayana area compared with the Assosa area (COR = 8.4, P = 0.00). Pfmdr1-N86Y wild type and 184F mutations were found in 79.8% (166/208) and 73.4% (146/199) samples, respectively. No single mutation was observed at the pfmdr1-1042 locus; however, 89.6% (190/212) of parasites in West Ethiopia carry the wild-type D1246Y variants. Eight pfmdr1 haplotypes at codons N86Y–Y184F–D1246Y were identified with the dominant NFD 61% (122/200). There was no difference in the distribution of pfmdr1 SNPs, haplotypes, and CNV between the two study sites (P > 0.05).

Conclusion

Plasmodium falciparum with the pfcrt wild-type haplotype was prevalent in high malaria transmission site than in low transmission area. The NFD haplotype was the predominant haplotype of the N86Y–Y184F–D1246Y. A continuous investigation is needed to closely monitor the changes in the pfmdr1 SNPs, which are associated with the selection of parasite populations by ACT.
CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth
Authors: Yang J. , Bergdorf K. , Yan C. , Luo W. , Chen S. C. , Ayers G.D. , Liu Q. , Liu X. , Boothby M. , Weiss V.L. , Groves S. M. , Oleskie A. N. , Zhang X. , Maeda D. Y. , Zebala J. A. , Quaranta V. , Richmond A.
Published: June 2023

Background

Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established.

Methods

To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter drivenBrafV600E/Pten−/−/Cxcr2−/−andNRasQ61R/INK4a−/−/Cxcr2−/−melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated inBrafV600E/Pten−/−andNRasQ61R/INK4a−/−mice and in melanoma cell lines. Potential mechanisms by whichCxcr2affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA).

Results

Genetic loss ofCxcr2or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, afterCxcr2ablation,Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2fold-change greater than 2 in these three different melanoma models.

Conclusions

Here, we provide novel mechanistic insight revealing how loss ofCxcr2expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor,Tfcp2l1,along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.
3D-printed hydrogel particles containing PRP laden with TDSCs promote tendon repair in a rat model of tendinopathy
Authors: Li Congsun , Wang Jie , Yang Weinan , Yu Kang , Hong Jianqiao , Ji Xiaoxiao , Yao Minjun , Li Sihao , Lu Jinwei , Chen Yazhou , Yan Shigui , Wu Haobo , Ma Chiyuan , Yu Xiaohua , Jiang Guangyao , Liu An
Published: June 2023

Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP–TDSC–GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP–TDSC–GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K–AKT pathway, thus promoting the structural and functional repair of tendons in vivo.

Graphical Abstract
Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial
Authors: Lv Xin , Ding Bo , Xu JingYun , Shen Yang
Published: June 2023

Background

The long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and effectiveness of the endocutter in radical laparoscopic hysterectomy for early cervical cancer.

Methods

A single-center, prospective, randomized controlled trial of modified radical laparoscopic hysterectomy on patients with FIGO stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer, between January 2020 and July 2021. Patients were randomly assigned into laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) groups. The ORH group used right-angle sealing forceps for vaginal stump closure, whereas the LRH group used endoscopic staplers. The primary outcomes included the evaluation of the patient’s perioperative indicators, as well as short- and long-term complications. Recurrence and overall survival were considered secondary outcomes.

Results

As of July 2021, 17 patients were enrolled in the laparoscopic surgery group and 17 in the open surgery group. The hospitalization time of the laparoscopic group was significantly shorter than those of the open group (15 min vs. 9 min, P < 0.001). The vaginal stump closure time in the laparoscopic group was longer than that in the open surgery group, and the difference was statistically significant (P < 0.001). Post-operative catheter removal (P = 0.72), drainage tube removal time (P = 0.27), number of lymph node dissections (P = 0.72), and incidence of intraoperative and post-operative complications between the two groups (P > 0.05). The median blood loss in the laparoscopic group was 278 ml, and it was 350 ml in the laparotomy group. The intraoperative blood transfusion rate was lower in the laparoscopic group; however, these differences did not reach statistical significance (P = 0.175). Vaginal margin pathology and peritoneal lavage cytology were negative, and all the patient’s vaginal stumps healed without infection. The median follow-up time of the laparoscopic group was 20.5 months, and it was 22 months for the open surgery group. There was no recurrence in all patients during the follow-up period.

Conclusions

Modified LRH with endocutter closure of the vaginal stump is an effective approach and not inferior to ORH in treating patients with early-stage cervical cancer.

Trial registration

ChiCTR2000030160, date of registration February 26, 2020 (https://www.chictr.org.cn/showprojen.aspx?proj=49809).
Preschool- and childcare center-based interventions to increase fruit and vegetable intake in preschool children in the United States: a systematic review of effectiveness and behavior change techniques
Authors: Hasan Faten , Nguyen Andy V. , Reynolds Amaya R. , You Wen , Zoellner Jamie , Nguyen Amanda J. , Swift Damon , Kranz Sibylle
Published: June 2023

Background

Fruit and vegetable (FV) consumption in children in the United States (US) is very low. Adequate FV consumption is required for proper development during childhood, and dietary habits are established during preschool-age and tend to persist into adulthood. As most U.S. preschool-aged children attend childcare or preschool, this may be an opportune time and setting to conduct interventions to improve FV intake. These interventions should be based in theory and use behavior change techniques (BCTs) to explain mechanisms for expected change. To date, no published reviews have examined the effectiveness of childcare- or preschool-based FV interventions in preschoolers and their use of theoretical frameworks and BCTs.

Methods

This systematic review was completed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were randomized controlled trials (RCTs) published between 2012 and 2022 of interventions to improve diet or FV intake in preschoolers (aged 2–5 years) in childcare or preschool-settings. A search of four databases was conducted between in September 2022 using search terms pertaining to the study’s primary aim (FV consumption), age group (preschool-aged), settings (US childcare or preschool settings), and study design (RCT). Additional criteria were objective measures of FV consumption or skin carotenoids, as a proxy for FV intake. Included studies were narratively synthesized based on intervention type, measured effect, and use of theory and BCTs.

Results

The search resulted in six studies that reported on nine interventions. Overall, six interventions increased FV intake, of which five used nutrition education and one manipulated the feeding environment. Among the three interventions with no measured effect, two manipulated the feeding environment and one used peer modeling. Effective studies used at least three BCTs, though no pattern was observed between use of theory or BCTs and intervention effect.

Conclusions

While several studies have shown promising results, the limited number of studies identified in this review highlights key gaps in this field: there is a need for studies to test FV interventions in US childcare settings that use objective measures of FV intake, directly compare intervention components and BCTs, are theory-based, and assess long-term behavior change.
The relevance of ototoxicity induced by radiotherapy
Authors: Huang Yan , Zhou Hong , An Fenglan , Zhao Aimei , Wu Jian , Wang Meihua , Luo Judong
Published: June 2023

Background

The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have undergone head-neck or brain radiation, or a combination of the two. To provide optimal care for these cancer survivors and minimize subsequent complications, it is crucial to comprehend the relationship between radiotherapy and ototoxicity.

Methods

A comprehensive search of databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was conducted from the inception of the knowledge base up until January 2023. The metafor-package was employed to compare ototoxicity rates in individuals receiving radiotherapy. Two independent assessors extracted data and analyzed targets using a random-effects model.

Results

Out of the 28 randomized controlled trials (RCTs) included in the analysis, 25 were prospective RCTs. Subgroup analysis revealed that mean cochlear radiation dose, primary tumor location, radiotherapy modality, and patient age significantly influenced total hearing impairment. Intensity-modulated radiotherapy was associated with less ototoxicity than 2D conventional radiotherapy (OR, 0.53; 95% CI, 0.47–0.60; P = 0.73; I2 = 0%). Stereotactic radiotherapy appeared to be a superior option for hearing preservation compared to radiosurgery (OR, 1.44; 95% CI, 1.00–2.07; P = 0.69; I2 = 0%). Children demonstrated a higher risk of hearing impairment than adults. More than 50% of patients with vestibular neuroadenoma experienced hearing impairment following radiation therapy. A strong association was observed between the average cochlear radiation dose and hearing impairment. Increased cochlear radiation doses may result in a heightened risk of hearing impairment.

Conclusion

Several risk factors for radiation-induced hearing impairment were identified in this study. High cochlear radiation doses were found to exacerbate the risk of hearing impairment resulting from radiation therapy.
Main and contralateral side stages of lesion affected bone union in the conservative treatment of adolescent lumbar spondylolysis: a multivariable analysis of 217 patients and 298 lesions in a retrospective cohort study
Authors: Gamada Hisanori , Tatsumura Masaki , Asai Reo , Okuwaki Shun , Funayama Toru , Yamazaki Masashi
Published: June 2023

Background

Factors affecting bone union in the conservative treatment of adolescent lumbar spondylolysis remain controversial. We aimed to examine these factors along with advances in diagnostic imaging using multivariable analysis of a sufficient number of patients and lesions.

Methods

In this retrospective study, high-school-aged patients or younger (n = 514) who were diagnosed with lumbar spondylolysis from 2014 to 2021 were investigated. We included patients with acute fractures who showed signal changes around the pedicle on magnetic resonance imaging and who completed conservative treatment. The following factors were investigated at the initial visit: age, sex, level of lesion, main side stage, presence and stage of contralateral side lesion, and presence of spina bifida occulta. The association of each factor with bone union was evaluated through a multivariable analysis.

Results

Altogether, 298 lesions in 217 patients (174 boys and 43 girls; mean age: 14.3 years) were included in this study. Multivariable logistic regression analysis of all factors showed that the main side progressive stage was more likely associated with nonunion as compared to the pre-lysis (OR: 5.86; 95% confidence interval [CI]: 2.00–18.8; p = 0.0011) and early stages (OR: 3.77; 95% CI: 1.72–8.46; p = 0.0009). Regarding the contralateral side stage, the terminal stage was more likely to be associated with nonunion.

Conclusion

In the conservative treatment of lumbar spondylolysis, the factors affecting bone union were the main and contralateral side stages. Sex, age, level of lesion, or spina bifida occulta had no significant effects on bone union. The main, progressive, and contralateral side terminal stages were negative predictors of bone union.

Trial registration This study was retrospectively registered.
Posterior intra-articular fixation stabilizes both primary and secondary sacroiliac joints: a cadaveric study and comparison to lateral trans-articular fixation literature
Authors: Sayed Dawood , Amirdelfan Kasra , Hunter Corey , Raji Oluwatodimu Richard
Published: June 2023

Background

Posterior and lateral techniques have been described as approaches to sacroiliac joint arthrodesis. The purpose of this study was to compare the stabilizing effects of a novel posterior stabilization implant and technique to a previously published lateral approach in a cadaveric multidirectional bending model. We hypothesized that both approaches would have an equivalent stabilizing effect in flexion–extension and that the posterior approach would exhibit better performance in lateral bending and axial rotation. We further hypothesized that unilateral and bilateral posterior fixation would stabilize both the primary and secondary joints.

Methods

Ranges of motion (RoMs) of six cadaveric sacroiliac joints were evaluated by an optical tracking system, in a multidirectional flexibility pure moment model, between ± 7.5 N-m applied moment in flexion–extension, lateral bending, and axial rotation under intact, unilateral fixation, and bilateral fixation conditions.

Results

Intact RoMs were equivalent between both samples. For the posterior intra-articular technique, unilateral fixation reduced the RoMs of both primary and secondary joints in all loading planes (flexion–extension RoM by 45%, lateral bending RoM by 47%, and axial RoM by 33%), and bilateral fixation maintained this stabilizing effect in both joints (flexion–extension at 48%, lateral bending at 53%, and axial rotation at 42%). For the lateral trans-articular technique, only bilateral fixation reduced mean RoM of both primary and secondary sacroiliac joints, and only under flexion–extension loads (60%).

Conclusion

During flexion–extension, the posterior approach is equivalent to the lateral approach, while producing superior stabilization during lateral bend and axial rotation.