bluuebunny/crossref_metadata_2025 huggingface dataset:
Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT
Authors: Sanz Jaime , Labopin Myriam , Choi Goda , Kulagin Alexander , Peccatori Jacopo , Vydra Jan , Reményi Péter , Versluis Jurjen , Rovira Montserrat , Blaise Didier , Labussière-Wallet Hélène , Montoro Juan , Sica Simona , Meijer Ellen , Itälä-Remes Maija , Schaap Nicolaas , Bulabois Claude Eric , Piemontese Simona , Mohty Mohamad , Ciceri Fabio
Published: April 2024

There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS). Overall, 1011 patients were included with a median age of 54 years (range, 18-77). Donors had a median age of 29 years (range, 18-64); 304 (30%) were females, of which 150 (15% of the whole group) were donors to male recipients, and 621 (61%) were MUDs; 522 (52%) had negative cytomegalovirus (CMV-neg) serostatus, of which 189 (19%) were used for CMV-neg recipients. Donor age older than 30 years had a negative impact on relapse (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.06-1.8), LFS (HR, 1.4; 95% CI, 1.12-1.74), overall survival (HR 1.45; 95% CI, 1.14-1.85) and graft-versus-host disease (GVHD) free, relapse-free survival (HR, 1.29; 95% CI, 1.07-1.56). In addition, CMV-neg donors for CMV-neg recipients were associated with improved LFS (HR, 0.74; 95% CI, 0.55-0.99). The use of MMUD and female donors for male recipients did not significantly impact any transplant outcomes. For patients undergoing HSCT from a UD with PTCy for AML, donor age <30 years significantly improves survival. In this context, donor age might be prioritized over HLA match considerations. In addition, CMV-neg donors are preferable for CMV-neg recipients. However, further research is needed to validate and refine these recommendations.
Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials
Authors: Kyriakopoulos Christos , Gogali Athena , Markozannes Georgios , Kostikas Konstantinos
Published: April 2024

Background:

Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab.

Methods:

We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety.

Results:

48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51–0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27–0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09–0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI −0.46–−0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26–0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile.

Conclusions:

This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.
Prognostic indicators of corneal ulcer clinical outcomes at a tertiary care center in the Bronx, New York
Authors: Kodali Sruthi , Khan Behram , Zong Amanda M. , Moon Jee-Young , Shrivastava Anurag , Daily Johanna P. , Gibralter Richard P.
Published: April 2024

Purpose

Corneal ulcers frequently result in ocular morbidity and may lead to permanent visual impairment if severe or untreated. This study aims to evaluate the association of patient factors and ocular exam findings on clinical outcomes for patients diagnosed with a corneal ulcer at a tertiary care center in the Bronx, New York.

Methods

A retrospective chart review was conducted on all ambulatory and admitted patients diagnosed with a corneal ulcer (identified using ICD-10 code H16.0) at Montefiore Medical Center, Bronx, NY between 2016–2022. Patient demographics, presence of known risk factors, characteristics of subsequent clinical course, and microbiological studies were noted. Clinical outcomes following treatment were longitudinally evaluated and categorized based upon the following criteria: 1) ‘No Surgical Intervention’: No severe complications or surgery required after presentation, 2) ‘Surgical Intervention’: Decline in BCVA with surgery required for a severe complication.

Results

The search criteria identified 205 patients (205 eyes) with the diagnosis of a corneal ulcer. Mean age was 55.3 ± 21.1 years (mean ± SD). Mean ulcer area at presentation was 7 ± 10.5 mm2. Mean LogMAR at presentation was 1.2 ± 1, and following treatment, improved to 1.0 ± 1. ‘Surgical Intervention’ outcome was associated with advanced age (p = 0.005), presence of ocular surface disease (p = 0.008), central location of ulcer (p = 0.014), greater ulcer area at presentation (p = 0.003), worse visual acuity at presentation (p < 0.001), and isolation of fungi (p = 0.004).

Conclusion

Identification of risk factors associated with a poor clinical prognosis can guide treatment and inform expectations for patients diagnosed with a corneal ulcer. Our study highlights the importance of timely diagnosis, work-up, and initiation of appropriate management, particularly in vulnerable populations where access to specialty care is logistically challenging.
Analysis and prediction of interactions between transmembrane and non-transmembrane proteins
Authors: Lu Chang , Jiang Jiuhong , Chen Qiufen , Liu Huanhuan , Ju Xingda , Wang Han
Published: April 2024

Background

Most of the important biological mechanisms and functions of transmembrane proteins (TMPs) are realized through their interactions with non-transmembrane proteins(nonTMPs). The interactions between TMPs and nonTMPs in cells play vital roles in intracellular signaling, energy metabolism, investigating membrane-crossing mechanisms, correlations between disease and drugs.

Results

Despite the importance of TMP-nonTMP interactions, the study of them remains in the wet experimental stage, lacking specific and comprehensive studies in the field of bioinformatics. To fill this gap, we performed a comprehensive statistical analysis of known TMP-nonTMP interactions and constructed a deep learning-based predictor to identify potential interactions. The statistical analysis describes known TMP-nonTMP interactions from various perspectives, such as distributions of species and protein families, enrichment of GO and KEGG pathways, as well as hub proteins and subnetwork modules in the PPI network. The predictor implemented by an end-to-end deep learning model can identify potential interactions from protein primary sequence information. The experimental results over the independent validation demonstrated considerable prediction performance with an MCC of 0.541.

Conclusions

To our knowledge, we were the first to focus on TMP-nonTMP interactions. We comprehensively analyzed them using bioinformatics methods and predicted them via deep learning-based solely on their sequence. This research completes a key link in the protein network, benefits the understanding of protein functions, and helps in pathogenesis studies of diseases and associated drug development.
Identification of different myofiber types in pigs muscles and construction of regulatory networks
Authors: Li Chenchen , Wang Yinuo , Sun Xiaohui , Yang Jinjin , Ren Yingchun , Jia Jinrui , Yang Gongshe , Liao Mingzhi , Jin Jianjun , Shi Xin’e
Published: April 2024

Background

Skeletal muscle is composed of muscle fibers with different physiological characteristics, which plays an important role in regulating skeletal muscle metabolism, movement and body homeostasis. The type of skeletal muscle fiber directly affects meat quality. However, the transcriptome and gene interactions between different types of muscle fibers are not well understood.

Results

In this paper, we selected 180-days-old Large White pigs and found that longissimus dorsi (LD) muscle was dominated by fast-fermenting myofibrils and soleus (SOL) muscle was dominated by slow-oxidizing myofibrils by frozen sections and related mRNA and protein assays. Here, we selected LD muscle and SOL muscle for transcriptomic sequencing, and identified 312 differentially expressed mRNA (DEmRs), 30 differentially expressed miRNA (DEmiRs), 183 differentially expressed lncRNA (DElRs), and 3417 differentially expressed circRNA (DEcRs). The ceRNA network included ssc-miR-378, ssc-miR-378b-3p, ssc-miR-24-3p, XR_308817, XR_308823, SMIM8, MAVS and FOS as multiple core nodes that play important roles in muscle development. Moreover, we found that different members of the miR-10 family expressed differently in oxidized and glycolytic muscle fibers, among which miR-10a-5p was highly expressed in glycolytic muscle fibers (LD) and could target MYBPH gene mRNA. Therefore, we speculate that miR-10a-5p may be involved in the transformation of muscle fiber types by targeting the MYHBP gene. In addition, PPI analysis of differentially expressed mRNA genes showed that ACTC1, ACTG2 and ACTN2 gene had the highest node degree, suggesting that this gene may play a key role in the regulatory network of muscle fiber type determination.

Conclusions

We can conclude that these genes play a key role in regulating muscle fiber type transformation. Our study provides transcriptomic profiles and ceRNA interaction networks for different muscle fiber types in pigs, providing reference for the transformation of pig muscle fiber types and the improvement of meat quality.
Occurrence, antibiotic resistance profiles and associated risk factors of Klebsiella pneumoniae in poultry farms in selected districts of Somalia Reginal State, Ethiopia
Authors: Kahin Mohamed Abdi , mohamed Abdimalik Hussein , Mohomed Ahmed Abdi , Hassan Mubarik Ali , Gebremeskel Haben Fesseha , Kebede Isayas Asefa
Published: April 2024

Background

Klebsiella pneumoniae is an opportunistic infection that causes production losses and death in the chicken industry. A cross-sectional study was conducted on exotic chicken breeds reared at the Jigjiga poultry farm from November 2022 to May 2023 to estimate the occurrence, associated risk factors, and antimicrobial susceptibility profiles of Klebsiella pneumoniae. The chickens were selected using systematic random sampling techniques. A total of 384 cloacal swabs were collected aseptically and transported to the laboratory for analysis. For statistical analysis, STATA® version 14.0 statistical software was used.

Results

From 384 examined faecal samples, 258 (67.2%) prevalences of Klebsiella pneumoniae were found. Furthermore, the association of the study’s risk factors with the prevalence of Klebsiella pneumoniae was explored, and no statistically significant association was identified between sex and age. Nonetheless, relative prevalence at the age level was higher in chickens aged 12 months (67.6%) and Sasso breeds (90.0%). Similarly, male chickens and those raised for meat and egg production had a high prevalence rate of 72.5 and 75.8%, respectively. A total of 30 isolated Klebsiella pneumoniae colonies were tested in vitro for antibiotic sensitivity for six drugs, and it was shown that Klebsiella pneumoniae is moderately sensitive to Penicillin G (43.3%) while having higher resistance to Oxytetracycline (80.0%).

Conclusions

The current findings revealed that the research area had the highest prevalence of Klebsiella pneumoniae, and the isolates were resistant to commonly used drugs in the study area. Thus, a long-term intervention plan, thorough research to determine a nationwide status, as well as further multi-drug resistance patterns and molecular characterization, were urged.
Overexpression of OsNAR2.1 by OsNAR2.1 promoter increases drought resistance by increasing the expression of OsPLDα1 in rice
Authors: Wang Yamei , Liu Hongyan , Bai Lu , Liu Ruifang , Jiang Hongzhen , Tan Jinfang , Chen Jingguang
Published: April 2024

Background

pOsNAR2.1:OsNAR2.1 expression could significantly increase nitrogen uptake efficiency and grain yield of rice.

Result

This study reported the effects of overexpression of OsNAR2.1 by OsNAR2.1 promoter on physiological and agronomic traits associated with drought tolerance. In comparison to the wild-type (WT), the pOsNAR2.1:OsNAR2.1 transgenic lines exhibited a significant improvement in survival rate when subjected to drought stress and then irrigation. Under limited water supply conditions, compared with WT, the photosynthesis and water use efficiency (WUE) of transgenic lines were increased by 39.2% and 28.8%, respectively. Finally, the transgenic lines had 25.5% and 66.4% higher grain yield than the WT under full watering and limited water supply conditions, respectively. Compared with the WT, the agronomic nitrogen use efficiency (NUE) of transgenic lines increased by 25.5% and 66.4% under full watering and limited water supply conditions, and the N recovery efficiency of transgenic lines increased by 29.3% and 50.2%, respectively. The interaction between OsNAR2.1 protein and OsPLDα1 protein was verified by yeast hybrids. After drought treatment, PLDα activity on the plasma membrane of the transgenic line increased 85.0% compared with WT.

Conclusion

These results indicated that pOsNAR2.1:OsNAR2.1 expression could improve the drought resistance of rice by increasing nitrogen uptake and regulating the expression of OsPLDα1.
Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study
Authors: Sun Yanqiu , Zhang Chenhong , He Bo , Wang Lei , Tian Dengfeng , Kang Zhiqiang , Chen Lixin , Li Ruiwen , Ren Jialiang , Guo Yong , Zhang Yonghai , Duojie Dingda , Zhang Qiang , Gao Fabao
Published: April 2024

Background

Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment.

Methods

6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan.

Results

The plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05).

Conclusions

After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.
Cross-cultural adaptation and psychometric evaluation of the social frailty scale in Iranian older adults
Authors: Zare Hanieh , Tagharrobi Zahra , Zare Mohammad
Published: April 2024

Background

Social frailty is a holistic concept encompassing various social determinants of health. Considering its importance and impact on health-related outcomes in older adults, the present study was conducted to cross-culturally adapt and psychometrically evaluate the Social Frailty Scale in Iranian older adults in 2023.

Methods

This was a methodological study. The translation and cross-cultural adaptation of the Social Frailty Scale 8-item (SFS-8) was conducted according to Wild’s guideline. Content and face validity were assessed using qualitative and quantitative methods. Then, 250 older adults covered by comprehensive health centers were selected using multistage random sampling. Participants completed the demographic questionnaire, the Abbreviated Mental Test score, the SFS-8, and the Lubben Social Network Scale. Construct validity was assessed by principal component analysis (PCA) and known-group comparisons. The Mann‒Whitney U test was used to compare social frailty scores between the isolated and non-isolated older adults. Internal consistency, equivalence, and stability were assessed using the Kuder-Richardson method, the intraclass correlation coefficient (ICC), the standard error of measurement (SEM), and the minimum detectable change (MDC). The ceiling and floor effects were also assessed. The data were analyzed using JASP 0.17.3.

Results

The ratio and index of content validity and the modified kappa coefficient of all the items were 1.00. The impact score of the items was greater than 4.6. PCA identified the scale as a single component by removing two questions that could explain 52.9% of the total variance in the scale score. The Persian version of the Social Frailty Scale could distinguish between isolated and non-isolated older adults (p < 0.001). The Kuder–Richardson coefficient, ICC, SEM, and MDC were 0.606, 0.904, 0.129, and 0.358, respectively. The relative frequencies of the minimum and maximum scores obtained from the scale were 34.8 and 1.2, respectively.

Conclusions

The Persian version of the Social Frailty Scale (P-SFS) can be used as a valid and reliable scale to assess social frailty in Iranian older adults.
Herpes zoster (HZ) vaccine coverage and confidence in Italy: a Nationwide cross-sectional study, the OBVIOUS project
Authors: Salussolia Aurelia , Capodici Angelo , Scognamiglio Francesca , La Fauci Giusy , Soldà Giorgia , Montalti Marco , Di Valerio Zeno , Fantini Maria Pia , Odone Anna , Costantino Claudio , Larson Heidi J. , Leask Julie , Lenzi Jacopo , Gori Davide ,   on behalf of the OBVIOUS board, Capodici Angelo , Conversano Michele , Costantino Claudio , Esposti Mirko Degli , Di Valerio Zeno , Fantini Maria Pia , Gori Davide , Grignolio Andrea , La Fauci Giusy , Larson Heidi J. , Leask Julie , Lenzi Jacopo , Montalti Marco , Odone Anna , Remondini Daniel , Scognamiglio Francesca , Salussolia Aurelia , Soldà Giorgia , Toth Federico , Vitale Francesco
Published: April 2024

Background

Herpes Zoster is an age dependent disease and as such it represents a problem in the Italian social context, where the demographic curve is characterized by an overrepresentation of the elderly population. Vaccines against Herpes Zoster are available, safe and effective, however coverage remains sub-optimal. This study was therefore conducted to examine the variations in Herpes Zoster vaccine uptake and confidence across different regions in Italy.

Methods

This study utilized a cross-sectional computer-assisted web interview (CAWI) methodology. The survey was conducted by Dynata, an online panel provider, and involved 10,000 respondents recruited in Italy between April 11 and May 29, 2022. The sample was stratified based on geographic region, gender, and age group. Data management adhered to European Union data protection regulations, and the survey covered demographics, living conditions, and vaccination against herpes zoster (HZ), following the BeSD framework.

Results

The findings indicate regional disparities in herpes zoster vaccine uptake across Italy. Notably, the Islands region exhibits a particularly low vaccination rate (2.9%), highlighting the need for targeted interventions. The multivariate regression analysis showed that sociodemographic factors, limited access to healthcare services, and inadequate awareness of vaccine eligibility contribute to the lower uptake observed in this region.

Conclusion

In conclusion, this research emphasizes regional disparities in herpes zoster (HZ) vaccination uptake in Italy. Demographic, socioeconomic, and geographic factors impact individuals’ willingness to receive the vaccine. The study highlights the importance of awareness of vaccine eligibility and accessible vaccination facilities in increasing uptake rates.
Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition
Authors: Obrișcă Bogdan , Mocanu Valentin , Jurubiță Roxana , Vrabie Alexandra , Berechet Andreea , Lujinschi Ștefan , Sorohan Bogdan , Andronesi Andreea , Achim Camelia , Lupușoru Gabriela , Micu Georgia , Caceaune Nicu , Gherghiceanu Mihaela , Ismail Gener
Published: April 2024

Background

There is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN.

Methods

We conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year.

Results

This cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m2 and 1.5 g/day (IQR:0.8–3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and − 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21–9.2).

Conclusions

We have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN.
Analysis of risk factors of preeclampsia in pregnant women with chronic hypertension and its impact on pregnancy outcomes
Authors: Nie Xiaorui , Xu Zijie , Ren Hong
Published: April 2024

Objective

To investigate the risk factors and maternal and fetal outcomes of preeclampsia after pregnancy in patients with primary chronic hypertension.

Methods

A total of 500 singleton pregnant women with a history of hypertension who were admitted for delivery at our Hospital from March 2015 to May 2022 were retrospectively collected by random sampling and divided into the non-occurrence group (n = 200) and the occurrence group (n = 300) according to whether they were complicated by preeclampsia. Afterward, the general data and the pregnancy-related data of patients were collected for comparison.

Results

The univariate analysis showed significant differences between the non-occurrence group and the occurrence group in terms of the proportion of preeclampsia history (4.00% VS 24.67%, χ2 = 37.383, P < 0.001), duration of hypertension > 3 years (18.00% VS 31.67%, χ2 = 11.592, P < 0.001), systemic therapy (20.50% VS 10.00%, χ2 = 10.859, P < 0.001), gestational age at admission [37.72 (34.10, 38.71) VS 35.01 (31.91, 37.42) weeks, Z = -9.825, P < 0.001]. Meanwhile, the multivariate analysis showed that a history of preeclampsia (OR = 6.796, 95% CI: 3.575 ∼ 10.134, χ2 = 8.234, P < 0.001), duration of hypertension > 3 years (OR = 3.456, 95% CI: 2.157 ∼ 5.161, χ2 = 9.348, P < 0.001), and a lack of systemic antihypertensive treatment (OR = 8.983, 95% CI: 7.735 ∼ 9.933, χ2 = 9.123, P < 0.001) were risk factors for chronic hypertension complicated by preeclampsia during pregnancy.

Conclusion

A history of preeclampsia, a longer duration of hypertension, and a lack of systematic antihypertensive treatment are risk factors for chronic hypertension complicated by preeclampsia during pregnancy. The occurrence of preeclampsia in pregnant women with chronic hypertension increases the incidence of maternal HELLP syndrome and fetal distress.
Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis
Authors: Qiu Yang , Bai Lu , Zhao Haosen , Mei Xifan
Published: April 2024

Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). The survival rate of AML patients is lower due to the cardiotoxicity of daunorubicin. Clinically, homoharringtonine (HHT) plus Ara-C has been reported to be equally effective as Dau plus Ara-C in some types of AML patients with less toxic effects. We utilized the clinical use of homoharringtonine in combination with Ara-C to test its combination mechanism. We found that the insensitivity of AML cells to cytarabine-induced apoptosis is associated with increased Mcl-1 stability and p38 inactivation. HHT downregulates Mcl-1, phosphorylates H2AX and induces apoptosis by activating p38 MAPK. Inactivation of p38 through inhibitors and siRNA blocks apoptosis, H2AX phosphorylation and Mcl-1 reduction. HHT enhances Ara-C activation of the p38 MAPK signalling pathway, overcoming Ara-C tolerance to cell apoptosis by regulating the p38/H2AX/Mcl-1 axis. The optimal ratio of HHT to Ara-C for synergistic lethality in AML cells is 1:4 (M/M). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.
Spatial disparity and associated factors of diarrhea among under-five children in Rwanda: a multilevel logistic regression analysis
Authors: Tareke Abiyu Abadi , Jemal Sebwedin Surur , Yemane Getahun Dejene , Zakaria Hamdi Fekredin , Shiferaw Enyew Woretaw , Ngabonzima Anaclet
Published: April 2024

Background

Diarrhea, defined as three or more loose stool per day, is a major cause of child mortality. Exploring its spatial distribution, prevalence, and influencing factors is crucial for public health decision and targeted interventions. This study aimed to investigate these aspects using 2019 Rwanda demographic health survey data.

Method

A total 7,978 (weighted) under-five children were included in this study. Spatial clustering (hotspots areas) were mapped using ArcGIS and SaTscan software. A multilevel logistic regression model was fitted to assessed factors associated with diarrhea, reporting significance at p < 0.05 and a 95% confidence interval.

Results

diarrheal diseases in Rwanda showed a clustered spatial pattern (Moran’s I = 0.126, p = 0.001), with the primary cluster in west and north provinces. Under-five diarrhea prevalence was 14.3% (95% CI: 13.55, 15.08). Factors increasing likelihood included maternal age 15–34 years, child age 7–24 months, while full immunization was protective (aOR = 0.74, 95% CI: 0.56, 0.98).

Conclusion

Spatial clustering of diarrheal diseases is found in west and north provinces of Rwanda. Being born to a young mother, being a child aged 7–24 months, being fully immunized, being born to a low-educated mother and belonging to a community having low level education are factors associated with diarrheal diseases in Rwanda. Developing interventional plans based on identified clusters and approaching children based on their immunization status, maternal education and age could be cost-effective in reducing diarrheal diseases in Rwanda. Location based intervention could allow for the efficient allocation of resources by focusing on areas with higher prevalence and need.
Relationship between cognitive function and functional outcomes in remitted major depression
Authors: Luo Ruiqing , Fan Ningdan , Dou Yikai , Wang Yu , Wang Min , Yang Xiao , Ma Xiaohong
Published: April 2024

Background

Few studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear.

Methods

Participants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission.

Results

According to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31–0.93, p = 0.030) and IED (95%CI = 1.01–1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes.

Conclusion

Better performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory.
Mental health markers and protective factors in students with symptoms of physical pain across WEIRD and non-WEIRD samples – a network analysis
Authors: Tandon Tanya , Piccolo Mayron , Ledermann Katharina , McNally Richard J. , Gupta Rashmi , Morina Naser , Martin-Soelch Chantal
Published: April 2024

Background

Studies conducted in Western societies have identified variables associated with chronic pain, but few have done so across cultures. Our study aimed to clarify the relationship between specific mental health markers (i.e., depression, anxiety, posttraumatic stress disorder [PTSD], perceived stress) as well as specific protective factors (i.e., social support and self-efficacy) related to physical pain among university students across non-WEIRD and WEIRD samples.

Method

A total of 188 university students (131 women and 57 men) were included in the study. We used network analysis to ascertain mental health markers especially central to the experience of physical pain.

Results

No statistically significant difference was found between mental health markers (i.e., depression, anxiety, perceived stress, and PTSD) and protective factors (i.e., social support and self-efficacy) associated with physical pain symptoms for Swiss students versus Indian students (M = 0.325, p = .11). In addition, networks for Swiss versus Indian students did not differ in global strength (S = 0.29, p = .803). Anxiety was the most central mental health marker, and social support was the most important protective factor related to physical pain in both countries. However, for Swiss students, perceived stress, and for Indian students, PTSD symptoms were central mental health markers related to physical pain.

Conclusion

Our results identify factors that may serve as important treatment targets for pain interventions among students of both countries before it becomes chronic.
Is economic growth enough to propel rehabilitation expenditures? An empirical analysis of country panel data and policy implications
Authors: Neill Rachel , Kautsar Hunied , Trujillo Antonio
Published: April 2024

Purpose

Rehabilitation is a set of services designed to increase functioning and improve wellbeing across the life course. Despite being a core part of Universal Health Coverage, rehabilitation services often receive limited public expenditure, especially in lower income countries. This leads to limited service availability and high out of pocket payments for populations in need of care. The purpose of this research was to assess the association between macroeconomic conditions and rehabilitation expenditures across low-, middle-, and high-income countries and to understand its implications for overall rehabilitation expenditure trajectory across countries.

Materials and methods

We utilized a panel data set from the World Health Organization’s Global Health Expenditure Database comprising the total rehabilitation expenditure for 88 countries from 2016 to 2018. Basic macroeconomic and population data served as control variables. Multiple regression models were implemented to measure the relationship between macroeconomic conditions and rehabilitation expenditures. We used four different model specifications to check the robustness of our estimates: pooled data models (or naïve model) without control, pooled data models with controls (or expanded naïve model), fixed effect models with all controls, and lag models with all controls. Log-log specifications using fixed effects and lag-dependent variable models were deemed the most appropriate and controlled for time-invariant differences.

Results

Our regression models indicate that, with a 1% increase in economic growth, rehabilitation expenditure would be associated with a 0.9% and 1.3% increase in expenditure. Given low baseline levels of existing rehabilitation expenditure, we anticipate that predicted increases in rehabilitation expenditure due to economic growth may be insufficient to meet the growing demand for rehabilitation services. Existing expenditures may also be vulnerable during periods of economic recession.

Conclusion

This is the first known estimation of the association between rehabilitation expenditure and macroeconomic conditions. Our findings demonstrate that rehabilitation is sensitive to macroeconomic fluctuations and the path dependency of past expenditures. This would suggest the importance of increased financial prioritization of rehabilitation services and improved institutional strengthening to expand access to rehabilitation services for populations.
Assessment of the integrated disease surveillance and response system implementation in health zones at risk for viral hemorrhagic fever outbreaks in North Kivu, Democratic Republic of the Congo, following a major Ebola outbreak, 2021
Authors: Kallay Ruth , Mbuyi Gisèle , Eggers Carrie , Coulibaly Soumaila , Kangoye David Tiga , Kubuya Janvier , Soke Gnakub Norbert , Mossoko Mathias , Kazambu Ditu , Magazani Alain , Fonjungo Peter , Luce Richard , Aruna Aaron
Published: April 2024

Background

The Democratic Republic of the Congo (DRC) experienced its largest Ebola Virus Disease Outbreak in 2018–2020. As a result of the outbreak, significant funding and international support were provided to Eastern DRC to improve disease surveillance. The Integrated Disease Surveillance and Response (IDSR) strategy has been used in the DRC as a framework to strengthen public health surveillance, and full implementation could be critical as the DRC continues to face threats of various epidemic-prone diseases. In 2021, the DRC initiated an IDSR assessment in North Kivu province to assess the capabilities of the public health system to detect and respond to new public health threats.

Methods

The study utilized a mixed-methods design consisting of quantitative and qualitative methods. Quantitative assessment of the performance in IDSR core functions was conducted at multiple levels of the tiered health system through a standardized questionnaire and analysis of health data. Qualitative data were also collected through observations, focus groups and open-ended questions. Data were collected at the North Kivu provincial public health office, five health zones, 66 healthcare facilities, and from community health workers in 15 health areas.

Results

Thirty-six percent of health facilities had no case definition documents and 53% had no blank case reporting forms, limiting identification and reporting. Data completeness and timeliness among health facilities were 53% and 75% overall but varied widely by health zone. While these indicators seemingly improved at the health zone level at 100% and 97% respectively, the health facility data feeding into the reporting structure were inconsistent. The use of electronic Integrated Disease Surveillance and Response is not widely implemented. Rapid response teams were generally available, but functionality was low with lack of guidance documents and long response times.

Conclusion

Support is needed at the lower levels of the public health system and to address specific zones with low performance. Limitations in materials, resources for communication and transportation, and workforce training continue to be challenges. This assessment highlights the need to move from outbreak-focused support and funding to building systems that can improve the long-term functionality of the routine disease surveillance system.
A case of hypercalcemia from Pneumocystis jirovecii in an immunosuppressed non-HIV patient
Authors: Gulhati Vishrut , Desy Janeve , Thornton Christina S.
Published: April 2024

Background

The prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ transplant recipients on immunosuppressive therapy presenting with mild hypercalcemia, leading to a diagnosis of PJP. Recent studies have shown efficacy of PJP prophylaxis for patients treated with rituximab with a favourable adverse effect profile.

Case Presentation

A 78-year-old male with a history of PR3-ANCA vasculitis, chronic kidney disease and heart failure with reduced ejection fraction presented to our tertiary care hospital with a two-week history of confusion and non-productive cough. Background immunosuppression with rituximab was completed every six months. The patient was found to have hypercalcemia and new infiltrates and ground glass opacities on cross-sectional imaging. Bronchoscopy was performed that was positive for Pneumocystis jirovecii. He was treated with 21 days of trimethoprim-sulfamethoxazole and prednisone with resolution of symptoms and hypercalcemia.

Conclusions

Herein, we present a novel case of PJP in a non-transplant recipient preceded by hypercalcemia. Our case demonstrates the importance for a high suspicion for PJP in chronically immunosuppressed patients on rituximab presenting with PTH-independent hypercalcemia.
Embosphere microspheres size for bronchial artery embolization in patients with hemoptysis caused by bronchiectasis: a retrospective comparative analysis of 500–750 versus 700–900 μm microspheres
Authors: Xu Hong-Dou , Yang Liang , Hu Shi-Bing
Published: April 2024

Background

Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE.

Methods

A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500–750 μm microspheres, and group B patients were treated with 700–900 μm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis.

Results

Median follow-up was 30.2 months (range, 20.3–56.5 months). The final analysis included a total of 112 patients (49–77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500–750 μm Embosphere microspheres, and group B (N = 44), which received 700–900 μm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12–2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10–2.72; P = 0.028) were independent risk factors for recurrent bleeding.

Conclusions

For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500–750 μm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700–900 μm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700–900 μm) Embosphere microspheres is associated with the reduced cost of an embolic agent.
Comparison of acute outcomes from elective total hip replacements and after fragility femoral neck fractures in nonagenarians
Authors: Al-Essah Zahra , Curlewis Keegan , Chan Gareth , Tokeisham Karim , Ghosh Koushik , Stott Philip , Rogers Benedict A.
Published: April 2024

Background

Hip hemiarthroplasty has traditionally been used to treat displaced femoral neck fractures in older, frailer patients whilst total hip replacements (THR) have been reserved for younger and fitter patients. However, not all elderly patients are frail, and some may be able to tolerate and benefit from an acute THR. Nonagenarians are a particularly heterogenous subpopulation of the elderly, with varying degrees of independence. Since THRs are performed electively as a routine treatment for osteoarthritis in the elderly, its safety is well established in the older patient. The aim of this study was to compare the safety of emergency THR to elective THR in nonagenarians.

Methods

A retrospective 10-year cohort study was conducted using data submitted to the National Hip Fracture Database (NHFD) across three hospitals in one large NHS Trust. Data was collected from 126 nonagenarians who underwent THRs between 1st January 2010 – 31st December 2020 and was categorised into emergency THR and elective THR groups. Mortality rates were compared between the two groups. Secondary outcomes were also compared including postoperative complications (dislocations, revision surgeries, and periprosthetic fracture), length of stay in hospital, and discharge destination.

Results

There was no significant difference in mortality between the two groups, with 1-year mortality rates of 11.4% and 12.1% reported for emergency and elective patients respectively (p = 0.848). There were no significant differences in postoperative complication rate and discharge destination. Patients who had emergency THR spent 5.56 days longer in hospital compared to elective patients (p = 0.015).

Conclusion

There is no increased risk of 1-year mortality in emergency THR compared to elective THR, in a nonagenarian population. Therefore, nonagenarians presenting with a hip fracture who would have been considered for a THR if presenting on an elective basis should not be precluded from an emergency THR on safety grounds.

Trial registration

Not necessary as this was deemed not to be clinical research, and was considered to be a service evaluation.