bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical analysis of the effect of doping with Na(I), K(I), Mg(II), Ca(II) and Fe(II) on the electronic and mechanical properties of pyrophyllite
Authors: Zhao Jian , Wang Yi-Fei , Luan Zhao-Long , Cao Yu , He Man-Chao
Published: August 2023

Pyrophyllite is an important layered phyllosilicate material that is used in many fields due to its beneficial physicochemical and mechanical properties. Due to the presence of multiple defects in pyrophyllite, an in-depth investigation was conducted using density functional theory to explore the effects of Na(I), K(I), Mg(II), Ca(II) and Fe(II) doping on the atomic structure, electronic properties and mechanical characteristics of pyrophyllite. The results demonstrated that, among the studied defects, K(I) doping had the most pronounced effects on the lattice constants and bonding lengths of pyrophyllite, while the least significant effects were observed in the case of Fe(II) doping. Moreover, the partial and total densities of states and band structures of the five kinds of doped pyrophyllite also changed significantly due to the redistribution of electrons. Finally, the elastic constants of the doped pyrophyllite were lower than that of the undoped pyrophyllite. Doping with Na(I), K(I), Mg(II), Ca(II) and Fe(II) reduced the deformation resistance, stiffness and elastic wave velocity but increased the degree of anisotropy in pyrophyllite. The observed effects on the mechanical properties of pyrophyllite followed the order: Mg(II) > Fe(II) > Ca(II) >K(I) > Na(I).
Desorption behaviour of polymers on sepiolite surfaces under high-temperature and high-salinity conditions
Authors: Lin Ling , Yang Yukun , Li Xin , Jiang Guobin , Luo Pingya
Published: August 2023

Polymers maintain colloidal stability by adsorbing onto the surface of sepiolite particles, and changes in temperature and salinity can affect this process. We chose three typical polymers to investigate their interactions with sepiolite under high-salinity (15 wt.% NaCl) conditions at >180°C. Sepiolite samples were characterized using infrared testing, X-ray diffraction testing, contact angle testing, thermogravimetric testing, filtration loss testing and rheological testing. The experimental results showed that the desorption of the polymers under high-temperature and high-salinity conditions reduces the stability and filtration control of the suspension significantly. Adding polymers to sepiolite suspensions can maintain good stability even after thermal ageing at 240°C. In terms of drilling fluid regulation, sepiolite can play a role in regulating rheological properties, and the interactions between various polymers and sepiolite can be utilized to maintain the stable colloidal state of the drilling fluid. Studying the adsorption behaviour of various types of polymers on the surface of sepiolite under high-temperature and high-salinity conditions has important implications for the design and selection of sepiolite drilling fluid treatment agents.
Sézary syndrome originates from heavily mutated hematopoietic progenitors
Authors: Harro Carly M. , Sprenger Kimberly B. , Chaurio Ricardo A. , Powers John J. , Innamarato Patrick , Anadon Carmen M. , Zhang Yumeng , Biswas Subir , Mandal Gunjan , Mine Jessica A. , Cortina Carla , Nagy Mate Z. , Martin Alexandra L. , Handley Katelyn F. , Borjas Gustavo J. , Chen Pei-Ling , Pinilla-Ibarz Javier , Sokol Lubomir , Yu Xiaoqing , Conejo-Garcia Jose R.
Published: August 2023

The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26−/CD7− lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-sequencing of 26,411 CD3+CD4+ and CD26+/CD7+ and 33 841 CD3+CD4+ and CD26−/CD7− lymphocytes, we show that tumor cells in Sézary syndrome and mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment. Surprisingly, we identified ≥200 mutations in hematopoietic stem cells from multiple patients with Sézary syndrome. Mutations in key oncogenes were also present in peripheral Sézary cells, which also showed the hallmarks of recent thymic egression. Together our data suggest that CTCL arises from mutated lymphocyte progenitors that acquire TCRs in the thymus, which complete their malignant transformation in the periphery.
Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study
Authors: Ansell Stephen M. , Bröckelmann Paul J. , von Keudell Gottfried , Lee Hun Ju , Santoro Armando , Zinzani Pier Luigi , Collins Graham P. , Cohen Jonathon B. , de Boer Jan Paul , Kuruvilla John , Savage Kerry J. , Trněný Marek , Provencio Mariano , Jäger Ulrich , Willenbacher Wolfgang , Wen Rachael , Akyol Alev , Mikita-Geoffroy Joanna , Shipp Margaret A. , Engert Andreas , Armand Philippe
Published: August 2023

Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) for whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase 2 CheckMate 205 trial. We present updated results (median follow-up, ∼5 years). Patients with R/R cHL who were brentuximab vedotin (BV)–naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C) were administered with nivolumab 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. Patients in cohort C with complete remission (CR) for 1 year could discontinue nivolumab and resume upon relapse. Among 243 patients (cohort A, n = 63; B, n = 80; and C, n = 100), the objective response rate (ORR) was 71.2% (95% confidence interval [CI], 65.1-76.8); the CR rate was 21.4% (95% CI, 16.4-27.1). Median duration of response, CR, and partial remission were 18.2 (95% CI, 14.7-26.1), 30.3, and 13.5 months, respectively. Median progression-free survival was 15.1 months (95% CI, 11.3-18.5). Median overall survival (OS) was not reached; OS at 5 years was 71.4% (95% CI, 64.8-77.1). In cohort C, all 3 patients who discontinued in CR and were subsequently re-treated achieved objective response. No new or unexpected safety signals were identified. This 5-year follow-up of CheckMate 205 demonstrated favorable OS and confirmed efficacy and safety of nivolumab in R/R cHL after auto-HCT failure. Results suggest patients may discontinue treatment after persistent CR and reinitiate upon progression. This trial was registered at www.clinicaltrials.gov as #NCT02181713.
Machine learning-based models for predicting mortality and acute kidney injury in critical pulmonary embolism
Authors: Wang Geng , Xu Jiatang , Lin Xixia , Lai Weijie , Lv Lin , Peng Senyi , Li Kechen , Luo Mingli , Chen Jiale , Zhu Dongxi , Chen Xiong , Yao Chen , Wu Shaoxu , Huang Kai
Published: August 2023

Objectives

We aimed to use machine learning (ML) algorithms to risk stratify the prognosis of critical pulmonary embolism (PE).

Material and methods

In total, 1229 patients were obtained from MIMIC-IV database. Main outcomes were set as all-cause mortality within 30 days. Logistic regression (LR) and simplified eXtreme gradient boosting (XGBoost) were applied for model constructions. We chose the final models based on their matching degree with data. To simplify the model and increase its usefulness, finally simplified models were built based on the most important 8 variables. Discrimination and calibration were exploited to evaluate the prediction ability. We stratified the risk groups based on risk estimate deciles.

Results

The simplified XGB model performed better in model discrimination, which AUC were 0.82 (95% CI: 0.78–0.87) in the validation cohort, compared with the AUC of simplified LR model (0.75 [95% CI: 0.69—0.80]). And XGB performed better than sPESI in the validation cohort. A new risk-classification based on XGB could accurately predict low-risk of mortality, and had high consistency with acknowledged risk scores.

Conclusions

ML models can accurately predict the 30-day mortality of critical PE patients, which could further be used to reduce the burden of ICU stay, decrease the mortality and improve the quality of life for critical PE patients.
Experiences of patients and next of kin on informed consent process for emergency surgery in two Urban university teaching hospitals in Uganda: a comparative cross sectional study
Authors: Kituuka Olivia , Mwaka Erisa , Munabi Ian , Galukande Moses
Published: August 2023

Informed consent for emergency surgery is a process in which a patient or their next of kin must make quick decisions required for surgery in a life-threatening situation or surgery that may have life-altering outcomes. The objective of the study was to describe patients and their next of kin experiences and factors influencing the informed consent process in two urban university teaching hospitals in Uganda. Methods: A cross-sectional survey involving patients who underwent emergency surgery and their next of kin was conducted in two tertiary care hospitals; one public and one private-not-for profit institution. A questionnaire was administered to collect sociodemographic information, type of Surgery that was done, how informed consent was obtained and experiences and expectations from the informed consent process. Univariate and multivariate analyses of the variables was done. Results: We collected data from 210 patients from a public hospital and 170 from a private-not-for profit hospital. Overall, most patients did not have the risks of the surgery communicated to them (79.7%), were not given alternative options (87.6%) and had no opportunity to ask questions (57.4%). Patients at the private institution had 3.35 times the odds of expecting the consent form to be explained to them than those at the public institution. Patients at the public hospital had 0.12 times the odds of preferring to have consent administered by a nurse than patients at the private institution OR 0.12 (0.05–0.29, p < 0.001). Patients in the public institution had 0.18 times the odds of preferring to have consent administered by a doctor than patients in the private institution OR 0.18 (0.08–0.45, p < 0.001). Conclusion: Patients in both public and private institutions are not informed about the risks of surgery, alternative options and are not given the opportunity to ask questions. Interpretation of the findings of this study on patient preferences on who administered consent though statistically significant were inconclusive due to the responses not being mutually exclusive.
Adverse perinatal outcomes after Roux-en-Y Gastric Bypass vs. Sleeve Gastrectomy: a systematic review
Authors: Kistner Astrid , Werner Alva , Zaigham Mehreen
Published: August 2023

Background

Pregnancies occurring after bariatric surgery are associated with various perinatal complications. However, there may be differences in the type of perinatal complications occurring after different methods of bariatric surgery. The aim of the current study was to compare adverse perinatal outcomes in pregnant women following Roux-en-Y Gastric Bypass (RYGB) vs. Sleeve Gastrectomy (SG).

Methods

A systematic database search was performed in PubMed, Embase, Scopus and CINAHL. Observational studies comparing perinatal outcomes post-bariatric (RYGB and SG) surgery to pregnancies without prior surgery were selected. Outcomes of interest were: maternal body mass index (BMI) at the time of conception, mode of delivery, time from surgery to conception, birth weight, gestational age and intrauterine fetal death. Article selection, risk of bias assessment and data extraction, were performed by two authors. The study protocol was published in its revised form in PROSPERO, registration number: CRD42021234480.

Results

A total of 3201 records were extracted. After duplicates were removed, 3143 records were screened for inclusion. Six studies fitted the selection criteria, of which four studies were RYGB and two SG (1100 post-RYGB vs. 209 post-SG). For the included studies, higher incidence of both SGA (22.9%, 11.9%, 14.2%) and LGA (4.2%, 4.8%, 1.7%) in SG compared to Roux-en-Y (SGA: 8.8%, 7.7%, 11.5%, 8.3% and LGA: 3.4%, 0.7%) were observed. SG had a shorter surgery to conception interval as compared to RYGB. Risk of bias assessment was moderate to serious for the studies included in the review, with bias in selection of participants being the major reason.

Conclusion

Our systematic review demonstrated no major differences in BMI, mode of delivery, birthweight, gestational age, or rates of intrauterine death between women having undergone RYGB vs. SG. The rate of SGA and LGA births were higher in the SG group, but this group also had a shorter surgery to conception interval. Future studies are indicated to counsel women of reproductive age on the most appropriate type of bariatric surgery that is associated with the best perinatal outcomes.
Comment: pregnancy after bariatric surgery – achievements and open questions
Authors: Göbl Christian S. , Feichtinger Michael , Henrich Wolfgang
Published: August 2023

Bariatric surgery confers potential advantages for obese patients, but also risks for pregnancy. Perinatal outcomes may be varying between surgical procedures. This topic was recently addressed by a systematic review in BMC Pregnancy and Childbirth. This commentary will discuss the scientific background and implications for future research.
Elective surgery cancellations in pediatric surgery: rate and reasons
Authors: Ben Mansour Maha , Lassioued Oussama , Chakroun Sawsen , Slimene Amine , Ben Youssef Sabrine , Ksiaa Amine , Gahbiche Mourad
Published: August 2023

Introduction

Canceling pediatric elective surgery leads to multiple disturbances regarding the inefficient operating room (OR) management, the financial repercussions, and the psychological impact on the patient and his family. This study aims to identify the reasons for cancellations among the pediatric population in our setting and suggest some convenient solutions.

Methods

We carried out a prospective and descriptive study over 12 months in the pediatric surgery department of Fattouma Bourguiba University Hospital.

Results

One thousand four hundred twenty-six patients were scheduled for surgery at the pediatric surgery department, of whom 131 (9.2%) were canceled. Medical and anesthesia-related reasons accounted for 62.5% of all cancellations, followed by surgical reasons at 16%, organizational or administrative issues at 11.5%, and patient-related reasons at 10%. The most significant causes were upper respiratory tract infections (URTIs) in 36.6%, abnormal blood test results in 16%, and non-adherence to preoperative fasting in 9.2%.

Conclusions

The rate of pediatric elective surgery cancellations at Fattouma Bourguiba University Hospital was higher than the accepted average rate (5%). Therefore, to prevent these cancellations as much as possible, efforts should be made to promote children’s medical care, operation scheduling, and efficient institution resource utilization.
Decrease in cognitive performance and increase of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with higher doses of antipsychotics in women with schizophrenia: a cross-sectional study
Authors: Frota Ilgner Justa , de Oliveira Alissandra Lima Barbosa , De Lima David Nunes , Costa Filho Carlos Winston Luz , Menezes Carlos Eduardo de Souza , Soares Michelle Verde Ramo , Chaves Filho Adriano José Maia , Lós Deniele Bezerra , Moreira Roberta Tavares de Araújo , Viana Glautemberg de Almeida , Campos Eugênio de Moura , Vasconcelos Silvânia Maria Mendes , Seeman Mary V. , Macêdo Danielle S. , Sanders Lia Lira Olivier
Published: August 2023

Background

We explored the relationship between symptoms, cognitive performance, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) (three markers of inflammation), and antipsychotic dose (in chlorpromazine units) in male and female patients with schizophrenia.

Methods

We conducted a cross-sectional analysis in patients with schizophrenia of the complete blood count and the results of neuropsychological testing, using the Welch t-test to compare groups and the Pearson test for correlations.

Results

We found that the NLR and the PLR are higher among women with schizophrenia when compared with men. In women, the NLR and the PLR correlate positively with antipsychotic drug dose and inversely with a working memory test (Direct Digit Span). Higher doses of antipsychotics are associated with worse working and semantic memory and mental flexibility in the women in our sample.

Conclusion

Higher doses of antipsychotics were associated with worse working and semantic memory and mental flexibility in women with schizophrenia. No such correlations were present in men, suggesting that, in female patients, cognitive performance deteriorates as the antipsychotic dose is increased, a finding that could be mediated by inflammatory mechanisms, given the demonstrated relationship to biomarkers of inflammation – e.g., the NLR and the PLR.

Trial registration

NCT03788759 (ClinicalTrials.gov).
Prevalence of chronic obstructive pulmonary disease and associated factors among small-holder fish vendors along coastal areas in Tanzania
Authors: Onesmo Brigitha M. , Mamuya Simon H. , Mwema Mwema Felix , Hella Jerry
Published: August 2023

Background

In Tanzania little is known about how the respiratory system of small-holder fish vendors is affected by occupational exposure to biomass smoke and other associated factors. This study assessed the prevalence of lung obstruction and associated factors among small-holder fish vendors along coastal areas in Tanzania.

Methods

A cross-sectional descriptive study was conducted in Bagamoyo and Kunduchi fish markets along coastal areas of Tanzania. Environmental air pollutant levels and composition were measured using a hand-held device. A standardized questionnaire was used to assess respiratory symptoms while EasyOne spirometer was used to test for lung function among small-holder fish vendors. Chronic Obstructive Pulmonary Disease (COPD) was defined as FEV1/FVC below the lower limit of normal. Data were analyzed using STATA Version 17. Descriptive statistics was performed and logistic regression analysis was used to determine factors that are associated with poor lung function presented as crude and adjusted odds ratio and their 95% confidence intervals.

Results

A total of 103 participants were included in the study who were predominantly males 82 (79.6%). The participants’ mean age was 35.47 (± 8.77 SD) years. The hourly average concentration levels of PM1, PM2.5, PM10, and CO exposure during fish frying were 653.6 (± 206.3 SD) μg/m3, 748.48 (± 200.6 SD) μg/m3, 798.66 (± 181.71 SD) μg/m3 and 62.6 (± 12.3 SD) ppm respectively which are higher than the WHO recommended limits. The prevalence of COPD was found to be 32.04% (95% CI 0.23–0.42). Most of the participants reported respiratory symptoms like coughing, wheezing, sputum production and breathlessness during performing their daily activities.

Conclusion

Findings suggest that three out of ten participants had COPD and the major environmental air pollutants (PMs and CO) concentration levels were too high, suggesting that occupational exposure to biomass smoke may be a risk factor. This calls for effective approaches to reduce exposure and prevent known acute and chronic respiratory diseases that are associated with such exposure to air pollutants. Also the study calls for follow up or cohort studies to be conducted in this area.
Committee experiences of using formal consensus in healthcare guidelines: a longitudinal qualitative study
Authors: Roberts V , Carter Patrice , Barnett P , Mugglestone MA , Pilling S
Published: August 2023

Background

This feasibility study has the primary aim of capturing and comparing participant expectations and experiences of using a formal consensus method (FCM) and to explore whether these views change following participation within a guideline committee where FCM are used.

Methods

Twelve healthcare committee members and associated technical team members participated in semi-structured qualitative interviews before and after using FCM during guideline committee meetings. Interviews also focused on past experiences and expectations of informal consensus methods.

Results

Participants said formal consensus included a greater range of evidence. They described positive reactions and found it a useful way to encourage involvement by balancing group power dynamics. Group discussion time was identified as important to clarify ideas, supported by good group chairing. However, participants reported that undertaking FCM required additional resources and suggested targeting its use for low quality evidence, limited committee expertise, or where the evidence is controversial.

Conclusions

FCM is an acceptable alternative to informal consensus methods that has qualities specifically helpful to healthcare guidelines such as encouraging participation, inclusivity of a broad range of evidence, and managing group dynamics. More research is required to better understand when using formal consensus is most appropriate and effective.
Study on risk factors of diabetic peripheral neuropathy and establishment of a prediction model by machine learning
Authors: Lian Xiaoyang , Qi Juanzhi , Yuan Mengqian , Li Xiaojie , Wang Ming , Li Gang , Yang Tao , Zhong Jingchen
Published: August 2023

Background

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Predicting the risk of developing DPN is important for clinical decision-making and designing clinical trials.

Methods

We retrospectively reviewed the data of 1278 patients with diabetes treated in two central hospitals from 2020 to 2022. The data included medical history, physical examination, and biochemical index test results. After feature selection and data balancing, the cohort was divided into training and internal validation datasets at a 7:3 ratio. Training was made in logistic regression, k-nearest neighbor, decision tree, naive bayes, random forest, and extreme gradient boosting (XGBoost) based on machine learning. The k-fold cross-validation was used for model assessment, and the accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC) were adopted to validate the models’ discrimination and clinical practicality. The SHapley Additive exPlanation (SHAP) was used to interpret the best-performing model.

Results

The XGBoost model outperformed other models, which had an accuracy of 0·746, precision of 0·765, recall of 0·711, F1-score of 0·736, and AUC of 0·813. The SHAP results indicated that age, disease duration, glycated hemoglobin, insulin resistance index, 24-h urine protein quantification, and urine protein concentration were risk factors for DPN, while the ratio between 2-h postprandial C-peptide and fasting C-peptide(C2/C0), total cholesterol, activated partial thromboplastin time, and creatinine were protective factors.

Conclusions

The machine learning approach helped established a DPN risk prediction model with good performance. The model identified the factors most closely related to DPN.
Inventory management practices: implications on the pharmaceuticals expenditure of rabies vaccine in public health facilities, Namibia
Authors: Shibabaw Alemnew Dessie , Nakambale Hilma N. , Bangalee Varsha
Published: August 2023

Background

To achieve well-regulated distribution, storage, and utilization of the rabies vaccine, health facilities should adhere to standard operating procedures. In Namibia, information on inventory management, utilization, monitoring, and reporting of rabies vaccine adherence to standard operating procedures in public healthcare facilities is insufficient. The aim of this study was to assess adherence to rabies vaccine standard operating procedures and inventory management and to compare rabies vaccine expenditure to the number of patients who received rabies vaccination at the Ministry of Health and Social Services’ public healthcare facilities from 2018 to 2020.

Methods

A cross-sectional, web-based questionnaire consisting of closed-ended questions was sent to 147 pharmacy staff and warehouse managers working in the 14 regions of Namibia during the period of May 1, 2021, to June 2, 2021. The overall expenditure and the total number of patients vaccinated from 2018 to 2020 were obtained from national-level logistic and vaccination program coordinators. Data were coded and transcribed into Microsoft® Excel® 2013 and analyzed using SPSS® version 27.

Results

One hundred and thirty-three completed questionnaires were received from sixty-nine public health centers and hospitals. The group of respondents consisted of pharmacist assistants (50%), pharmacy technicians (12%), pharmacists (36.8%), senior pharmacists (0.8%), and chief pharmacists (1.5%). Overall, adherence to standard operating procedures was poor (27.1%). Rabies vaccine distributed to public health facilities from 2018 to 2020 was worth N$75,381,419.91 (~ US$4,074,671.46) and was expected to vaccinate 87,269 patients; however, only 95 cases of both rabies and rabid dog-bite patients were reported. The major inventory management challenges for public healthcare facilities include an inadequate number of pharmacy staff, poor adherence to standardized pharmaceutical warehousing, lack of regular supervision, and inadequate staff training.

Conclusion

Inventory management practices in public healthcare facilities were not in compliance with standard operating procedures. There is a significant discrepancy between rabies vaccine expenditure and the number of patients that were vaccinated. Therefore, there is a need for adequate staff training on inventory management and regular facility supervision to enforce optimal rabies vaccine inventory management practices.
Leprosy and tuberculosis control scenario of the national program for the improvement of access and quality of primary care in Brazil
Authors: Ferreira Glenda R. O. N. , Miranda Amanda L. C. , Farias Viviane A. , Martins Melissa B. , Neri Débora Talitha , Borges William D. , Cunha Carlos Leonardo F. , Dias Geyse Aline R. , Santos Dirceu C. , Sousa Fabianne J. D.
Published: August 2023

Background

In Brazil, despite advances in public health policies aimed at eliminating and controlling infectious and parasitic diseases, the incidence of neglected diseases is still high. The epidemiological scenario in Brazil of diseases such as tuberculosis and leprosy evidences a public policy agenda that has not been resolute in terms of control, nor in terms of elimination.

Objective

To analyze the actions of diagnosis and treatment of leprosy and tuberculosis in the context of primary health care.

Methods

In this ecological study, data from the third cycle of the Program for the Improvement of Access and Quality of Primary Care were extracted from electronic address of the Primary Health Care Secretariat of Brazil in the area of Actions, Programs and Strategies. A total of 37,350 primary health care teams were that answered the questionnaire were eligible, with variables extracted from leprosy and tuberculosis control actions. The municipalities were grouped according to the characteristic of the Brazilian municipality. The partition chi-square and the Residuals Test were used to assess whether there was a difference in the proportion of tuberculosis and leprosy actions between types of municipalities. Statistics were carried out using Minitab 20 and Bioestat 5.3.

Results

Regarding the leprosy treatment location, there is a higher proportion of people referred to be treated at the reference in adjacent rural (p = 0.0097) and urban (p < 0.0001) municipalities; monitoring of people with leprosy referred to the service network (p. = 0.0057) in remote rural areas. Lower proportion of teams requesting bacilloscopy in remote rural areas (p = 0.0019). Rural areas have a higher proportion of teams that diagnose new cases (p = 0.0004). Regarding the actions of diagnosis and treatment of tuberculosis. There is a higher proportion of teams that carry out consultations at the unit itself in rural areas when compared to adjacent intermediaries (p = 0.0099) and urban (p < 0.0001); who requested sputum smear microscopy in adjacent intermediaries (p = 0.0021); X-ray in adjacent intermediaries (p < 0.0001) and urban (p < 0.0001); collection of the first sputum sample in urban (p < 0.0001) and adjacent rural areas (p < 0.0001); directly observed treatment (p < 0.0001) in adjacent rural municipalities.

Conclusion

There are inequalities in the diagnosis and treatment of leprosy and tuberculosis among the types of municipalities.
Ageing as risk factor for tinnitus and its complex interplay with hearing loss—evidence from online and NHANES data
Authors: Reisinger Lisa , Schmidt Fabian , Benz Kaja , Vignali Lorenzo , Roesch Sebastian , Kronbichler Martin , Weisz Nathan
Published: August 2023

Background

Tinnitus affects 10 to 15% of the population, but its underlying causes are not yet fully understood. Hearing loss has been established as the most important risk factor. Ageing is also known to accompany increased prevalence; however, the risk is normally seen in context with (age-related) hearing loss. Whether ageing per se is a risk factor has not yet been established. We specifically focused on the effect of ageing and the relationship between age, hearing loss, and tinnitus.

Methods

We used two samples for our analyses. The first, exploratory analyses comprised 2249 Austrian individuals. The second included data from 16,008 people, drawn from a publicly available dataset (NHANES). We used logistic regressions to investigate the effect of age on tinnitus.

Results

In both samples, ageing per se was found to be a significant predictor of tinnitus. In the more decisive NHANES sample, there was an additional interaction effect between age and hearing loss. Odds ratio analyses show that per unit increase of hearing loss, the odds of reporting tinnitus is higher in older people (1.06 vs 1.03).

Conclusions

Expanding previous findings of hearing loss as the main risk factor for tinnitus, we established ageing as a risk factor in its own right. Underlying mechanisms remain unclear, and this work calls for urgent research efforts to link biological ageing processes, hearing loss, and tinnitus. We therefore suggest a novel working hypothesis that integrates these aspects from an ageing brain viewpoint.
Lack of durable natriuresis and objective decongestion following SGLT2 inhibition in randomized controlled trials of patients with heart failure
Authors: Packer Milton
Published: August 2023

Patients with heart failure have increased cardiac filling pressures, circulating natriuretic peptides, and physical signs of fluid retention, which are related to sodium retention by the kidneys and are alleviated by conventional diuretics. Sodium-glucose cotransporter 2 (SGLT2) inhibitors interfere with sodium and glucose reabsorption in the proximal renal tubule, but they evoke a marked counterregulatory activation of sodium and water reabsorption in distal nephron segments, which opposes and negates any diuretic effect. Nevertheless, it has been postulated that SGLT2 inhibitors modulate the volume set point, leading selectively to decongestion in patients with fluid overload. This hypothesis was tested in a review of 15 randomized controlled trials of SGLT2 inhibitors in patients with heart failure, with 7 trials focusing on urinary volume within the first week, and 8 trials focusing on objective decongestion at 12 weeks. In trials < 1 week, SGLT2 inhibition increased urine volume in the first 24 h, but typically without a change in urinary sodium excretion, and this diuresis was not sustained. In 8 trials of 12 weeks’ duration, none reported alleviation of edema, ascites or pulmonary rales. The 2 trials that evaluated changes in left ventricular filling pressure noted no or small changes (1–2 mm Hg); the two trials that measured interstitial lung water or total blood volume found no effect; and 6 of the 7 trials found no decrease in circulating natriuretic peptides. Therefore, randomized controlled trials do not indicate that SGLT2 inhibitors produce a durable natriuresis or objective decongestion in patients with heart failure.
Nano-engineering nanomedicines with customized functions for tumor treatment applications
Authors: Wang Yuxin , Li Shimei , Ren Xiangling , Yu Shiping , Meng Xianwei
Published: August 2023

Nano-engineering with unique “custom function” capability has shown great potential in solving technical difficulties of nanomaterials in tumor treatment. Through tuning the size and surface properties controllablly, nanoparticles can be endoewd with tailored structure, and then the characteristic functions to improve the therapeutic effect of nanomedicines. Based on nano-engineering, many have been carried out to advance nano-engineering nanomedicine. In this review, the main research related to cancer therapy attached to the development of nanoengineering nanomedicines has been presented as follows. Firstly, therapeutic agents that target to tumor area can exert the therapeutic effect effectively. Secondly, drug resistance of tumor cells can be overcome to enhance the efficacy. Thirdly, remodeling the immunosuppressive microenvironment makes the therapeutic agents work with the autoimmune system to eliminate the primary tumor and then prevent tumor recurrence and metastasis. Finally, the development prospects of nano-engineering nanomedicine are also outlined.
Heterotypic tumor spheroids: a platform for nanomedicine evaluation
Authors: Vakhshiteh Faezeh , Bagheri Zeinab , Soleimani Marziye , Ahvaraki Akram , Pournemat Parisa , Alavi Seyed Ebrahim , Madjd Zahra
Published: August 2023

Nanomedicine has emerged as a promising therapeutic approach, but its translation to the clinic has been hindered by the lack of cellular models to anticipate how tumor cells will respond to therapy. Three-dimensional (3D) cell culture models are thought to more accurately recapitulate key features of primary tumors than two-dimensional (2D) cultures. Heterotypic 3D tumor spheroids, composed of multiple cell types, have become more popular than homotypic spheroids, which consist of a single cell type, as a superior model for mimicking in vivo tumor heterogeneity and physiology. The stromal interactions demonstrated in heterotypic 3D tumor spheroids can affect various aspects, including response to therapy, cancer progression, nanomedicine penetration, and drug resistance. Accordingly, to design more effective anticancer nanomedicinal therapeutics, not only tumor cells but also stromal cells (e.g., fibroblasts and immune cells) should be considered to create a more physiologically relevant in vivo microenvironment. This review aims to demonstrate current knowledge of heterotypic 3D tumor spheroids in cancer research, to illustrate current advances in utilizing these tumor models as a novel and versatile platform for in vitro evaluation of nanomedicine-based therapeutics in cancer research, and to discuss challenges, guidelines, and future directions in this field.

Graphical Abstract
Equity and trends in general practitioners’ allocation in China: based on ten years of data from 2012 to 2021
Authors: Kou Ruxin , Mei Kangni , Bi Yuqing , Huang Jingwen , Yang Shilan , Chen Kexuan , Li Wei
Published: August 2023

Background

General practitioners (GP) are the gatekeepers of residents' health, 2021 is the 10th year of the establishment of the GP system in China. This study aims to assess the equity and trends of GP allocation in China from 2012 to 2021, summarize the efforts and progress of GPs in China during the decade, predict the development trend of GPs in mainland China in the next 5 years to provide a reference for regional health planning and rational allocation of GPs in China.

Methods

Data from 2012 to 2021 on GPs in 22 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in mainland China (excluding Hong Kong, Macao, and Taiwan) are collected by us. Gini coefficient, Lorenz curve and health resource agglomeration degree (HRAD) were used to analyze the equity of the allocation of GPs in China from different dimensions, a Grey prediction model was used to forecast the number of GPs in 2022–2026.

Results

The number of GPs in mainland China increased from 109 794 to 434 868 from 2012 to 2021, with 3.08 GPs per 10 000 people in 2021. The Gini coefficient of GPs allocation by population in China decreased from 0.312 to 0.147 from 2012 to 2021, while the Gini coefficient of geographic dimension remained between 0.700 and 0.750. Compared with the degree of curvature of the Lorenz curve in the geographic dimension, the degree of curvature of the population and economic dimension were smaller. In 2021, the HRAD in the Eastern region was 4.618, the Central region was 1.493, with different degrees of imbalance among regions, the HRAD/PAD (population agglomeration degree) in the Eastern, Central and Western regions were 1.196, 0.880 and 0.821, respectively. GPs in the Eastern region is still concentrated, while the Central and Western regions were at a similar level, GPs were more scarce. The GM (1,1) model predicts that the number of GPs in mainland China will reach about 720 000 in 2026, the number of GPs per 10 000 people will reach 4.9.

Conclusion

After a decade of development, the number of GPs in China has increased significantly. It has reached the goal of the GP system when it was first established. However, the equity of the geographical dimension, both in terms of Gini coefficient and HRAD, has great differences between different regions. The average Gini coefficient at the geographic dimension is 0.723. The average HRAD index was 4.969 in the East and 0.293 in the West. The Western region has the problem of insufficient GP allocation in both population and geographical dimension. In the future, the number of GPs in China will continue to grow rapidly with the support of policies. The “2030” goal, proposed in 2018, is expected to be achieved by 2026. Due to certain factors (such as COVID-19), the actual situation may be different from the predicted results.
Prmt5 deficiency inhibits CD4+ T-cell Klf2/S1pr1 expression and ameliorates EAE disease
Authors: Zheng Yingxia , Chen Zheyi , Zhou Bingqian , Chen Shiyu , Chen Ningdai , Shen Lisong
Published: August 2023

Background

Protein arginine methyltransferase 5 (Prmt5) is the main type II methyltransferase, catalyzes protein arginine residue symmetric dimethylation, and modulates normal cellular physiology and disease progression. Prmt5 inhibition or deletion in CD4+ T cells has been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), but the detailed molecular mechanisms have not yet been elucidated.

Methods

EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35–55) in T cells Prmt5 conditional knockout (CD4-cre-Prmt5fl/fl, Prmt5cko) and Prmt5fl/fl (WT) mice. Flow cytometry, single-cell RNA sequencing, ATAC sequencing and chromatin immunoprecipitation assay (ChIP) approaches were used to explore the detail mechanisms.

Results

We find that Prmt5cko mice are resistant to EAE; infiltrating inflammatory CD4+ T cells in the central nervous system (CNS) are greatly reduced. However, in Prmt5cko mice, T cells in the spleen show much more proliferation and activation properties, the total number of CD4+ T cells in the spleen is not reduced, and the percentage of Rora+ CD4+ T cells is elevated. Also, CD4+ T cells express lower levels of S1pr1 and Klf2 than WT mice, which may influence pathogenic CD4+ T-cell egress from the spleen and migration to the CNS. Moreover, the single-cell ATAC sequence and ChIP assay reveal that the transcription factor Klf2 is enriched at the S1pr1 promoter and that Klf2 motif activity is reduced in Prmt5cko mice.

Conclusions

Our study delineates the undiscovered role of Prmt5 in T-cell biology in which Prmt5 may inhibit Klf2-S1pr1 pathway to ameliorate EAE disease. Controlling T-cell Prmt5 expression may be helpful for the treatment of autoimmune diseases.
Intracortical and intercortical networks in patients after stroke: a concurrent TMS-EEG study
Authors: Bai Zhongfei , Zhang Jack Jiaqi , Fong Kenneth N. K.
Published: August 2023

Background

Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) recording provides information on both intracortical reorganization and networking, and that information could yield new insights into post-stroke neuroplasticity. However, a comprehensive investigation using both concurrent TMS-EEG and motor-evoked potential-based outcomes has not been carried out in patients with chronic stroke. Therefore, this study sought to investigate the intracortical and network neurophysiological features of patients with chronic stroke, using concurrent TMS-EEG and motor-evoked potential-based outcomes.

Methods

A battery of motor-evoked potential-based measures and concurrent TMS-EEG recording were performed in 23 patients with chronic stroke and 21 age-matched healthy controls.

Results

The ipsilesional primary motor cortex (M1) of the patients with stroke showed significantly higher resting motor threshold (P = 0.002), reduced active motor-evoked potential amplitudes (P = 0.001) and a prolonged cortical silent period (P = 0.007), compared with their contralesional M1. The ipsilesional stimulation also produced a reduction in N100 amplitude of TMS-evoked potentials around the stimulated M1 (P = 0.007), which was significantly correlated with the ipsilesional resting motor threshold (P = 0.011) and motor-evoked potential amplitudes (P = 0.020). In addition, TMS-related oscillatory power was significantly reduced over the ipsilesional midline-prefrontal and parietal regions. Both intra/interhemispheric connectivity and network measures in the theta band were significantly reduced in the ipsilesional hemisphere compared with those in the contralesional hemisphere.

Conclusions

The ipsilesional M1 demonstrated impaired GABA-B receptor-mediated intracortical inhibition characterized by reduced duration, but reduced magnitude. The N100 of TMS-evoked potentials appears to be a useful biomarker of post-stroke recovery.
Detection of human adenoviruses in influenza-negative patients with respiratory tract infections in Nanning, China
Authors: Qin Jianqiu , Yan Tengyue , Yin Liujiang , Yang Cheng , Wang Liang , Qiu Hong , Hu Yanling , Xu Bin
Published: August 2023

Background

Human adenoviruses (HAdV) have been known to cause a range of diseases, including respiratory tract infections (RTIs). However, there is limited information available regarding the genotype diversity and epidemiology of HAdV associated with RTIs in Nanning.

Methods

Between June 2019 and December 2021, throat swab, nasal swab, or nasopharyngeal swab samples were obtained from individuals hospitalized with respiratory tract infections (RTIs). Statistical software was used to analyze the epidemiological data. The highly conserved 132-bp gene region of the HAdV hexon was targeted for the detection of HAdV using a qPCR assay. An 875-bp hexon gene fragment was subjected to phylogenetic analysis.

Results

Significant variations were observed in the age and gender distribution of HAdV-positive patients (P = 0.004 and P = 0.025, respectively). The age distribution of HAdV-positive patients showed that 67.89% of those who tested positive were the age group of 0–6 years. Furthermore, the prevalence of HAdV detection was highest during spring and autumn, with a peak in February. Additionally, genotyping of the 36 HAdV-positive samples with 875-bp fragments identified the presence of circulating HAdV species B, C, and E in Nanning between 2019 and 2021.

Conclusions

This study identified an association between HAdV prevalence and age as well as season. Among hospitalized patients with RTIs in Nanning, HAdV-B, HAdV-C, and HAdV-E were found to be co-circulating. The most commonly detected genotypes were HAdV-C1, HAdV-C6, and HAdV-E4.
Methyltransferase-like proteins in cancer biology and potential therapeutic targeting
Authors: Qi Ya-Nan , Liu Zhu , Hong Lian-Lian , Li Pei , Ling Zhi-Qiang
Published: August 2023

RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family of proteins plays a critical role in RNA modification, methylating various types of RNAs, including mRNA, tRNA, microRNA, rRNA, and mitochondrial RNAs. METTL proteins consist of a unique seven-beta-strand domain, which binds to the methyl donor SAM to catalyze methyl transfer. The most typical family member METTL3/METTL14 forms a methyltransferase complex involved in N6-methyladenosine (m6A) modification of RNA, regulating tumor proliferation, metastasis and invasion, immunotherapy resistance, and metabolic reprogramming of tumor cells. METTL1, METTL4, METTL5, and METTL16 have also been recently identified to have some regulatory ability in tumorigenesis, and the rest of the METTL family members rely on their methyltransferase activity for methylation of different nucleotides, proteins, and small molecules, which regulate translation and affect processes such as cell differentiation and development. Herein, we summarize the literature on METTLs in the last three years to elucidate their roles in human cancers and provide a theoretical basis for their future use as potential therapeutic targets.
CT and MRI imaging in Sweden: retrospective appropriateness analysis of large referral samples
Authors: Ståhlbrandt Henriettæ , Björnfot Ida , Cederlund Torsten , Almén Anja
Published: August 2023

Objectives

The numbers of computed tomography (CT) and magnetic resonance imaging (MRI) examinations per capita continue to increase in Sweden and in other parts of Europe. The appropriateness of CT and MRI examinations was audited using established European appropriateness criteria. Alternative modalities were also explored. The results were compared with those of a previous study performed in Sweden.

Methods

A semi-automatic retrospective evaluation of referrals from examinations performed in four healthcare regions using the European appropriateness criteria in ESR iGuide was undertaken. The clinical indications from a total of 13,075 referrals were assessed against these criteria. The ESR iGuide was used to identify alternative modalities resulting in a higher degree of appropriateness. A qualitative comparison with re-evaluated results from the previous study was made.

Results

The appropriateness was higher for MRI examinations than for CT examinations with procedures classed as usually appropriate for 76% and 63% of the examinations, respectively. The degree of appropriateness for CT was higher for referrals from hospitals compared to those from primary care centres. The opposite was found for MRI examinations. The alternative modalities that would result in higher appropriateness included all main imaging modalities. The result for CT did not show improvement compared with the former study.

Conclusions

A high proportion of both CT and MRI examinations were inappropriate. The study indicates that 37% of CT examinations and 24% of MRI examinations were inappropriate and that the appropriateness for CT has not improved in the last 15 years.

Critical relevance statement

A high proportion of CT and MRI examinations in this retrospective study using evidence-based referral guidelines were inappropriate.

Key points

∙ A high proportion of CT and MRI examinations were inappropriate.

∙ The CT referrals from general practitioners were less appropriate that those from hospital specialists.

∙ The MRI referrals from hospital specialists were less appropriate that those from general practitioners.

∙ Adherence to radiological appropriateness guidelines may improve the appropriateness of conducted examinations.

Graphical abstract