bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of prognostic models for small cell lung cancer patients with liver metastasis: a SEER population-based study
Authors: Li Qiaofeng , Zhao Yandong , Xu Zheng , Ma Yongqing , Wu Chengyu , Shi Huayue
Published: January 2024

Background

This study was to establish and validate prediction models to predict the cancer-specific survival (CSS) and overall survival (OS) of small-cell lung cancer (SCLC) patients with liver metastasis.

Methods

In the retrospective cohort study, SCLC patients with liver metastasis between 2010 and 2015 were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training group and testing group (3: 1 ratio). The Cox proportional hazards model was used to determine the predictive factors for CSS and OS in SCLC with liver metastasis. The prediction models were conducted based on the predictive factors. The performances of the prediction models were evaluated by concordance indexes (C-index), and calibration plots. The clinical value of the models was evaluated by decision curve analysis (DCA).

Results

In total, 8,587 patients were included, with 154 patients experiencing CSS and 154 patients experiencing OS. The median follow-up was 3 months. Age, gender, marital status, N stage, lung metastases, multiple metastases surgery of metastatic site, chemotherapy, and radiotherapy were independent predictive factors for the CSS and OS of SCLC patients with liver metastasis. The prediction models presented good performances of CSS and OS among patients with liver metastasis, with the C-index for CSS being 0.724, whereas the C-index for OS was 0.732, in the training set. The calibration curve showed a high degree of consistency between the actual and predicted CSS and OS. DCA suggested that the prediction models provided greater net clinical benefit to these patients.

Conclusion

Our prediction models showed good predictive performance for the CSS and OS among SCLC patients with liver metastasis. Our developed nomograms may help clinicians predict CSS and OS in SCLC patients with liver metastasis.
The role of cannabinoid receptor 2 in bone remodeling during orthodontic tooth movement
Authors: Fan Deng-ying , Zhai Hao-yan , Zhao Yuan , Qiao Xing , Zhu De-chao , Liu Hui-Juan , Liu Chunyan
Published: January 2024

Background

The purpose of this study is to explore the effects of CB2 on bone regulation during orthodontic tooth movement.

Methods

Thirty male mice were allocated into 2 groups (n = 15 in each group): wild type (WT) group and CB2 knockout (CB2−/−) group. Orthodontic tooth movement (OTM) was induced by applying a nickel-titanium coil spring between the maxillary first molar and the central incisors. There are three subgroups within the WT groups (0, 7 and 14 days) and the CB2−/− groups (0, 7 and 14 days). 0-day groups without force application. Tooth displacement, alveolar bone mass and alveolar bone volume were assessed by micro-CT on 0, 7 and 14 days, and the number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the expression levels of RANKL and OPG in the compression area were measured histomorphometrically.

Results

The WT group exhibited the typical pattern of OTM, characterized by narrowed periodontal space and bone resorption on the compression area. In contrast, the accelerated tooth displacement, increased osteoclast number (P < 0.0001) and bone resorption on the compression area in CB2−/− group. Additionally, the expression of RANKL was significantly upregulated, while OPG showed low levels in the compression area of the CB2 − / − group (P < 0.0001).

Conclusions

CB2 modulated OTM and bone remodeling through regulating osteoclast activity and RANKL/OPG balance.
Association between DMFT and primary headaches: a study based on the Rafsanjan cohort study
Authors: Ayoobi Fatemeh , khalili Parvin , Jamali Zahra , Moghaddam Sogand Esmaeil , Sardari Farimah , Vakilian Alireza
Published: January 2024

Background

Although primary headaches are common disorders, there is little research on the possible relationship between primary headaches and oral health (decayed, missing, and filled teeth: DMFT). The present study aims to investigate the relationship between the DMFT index and primary headaches.

Method

This descriptive study was performed on 8682 cases from the Rafsanjani cohort population based on the Rafsanjani cohort study (RCS) and Oral Health Branch of the Rafsanjan Cohort Study (OHBRCS). Episodic primary headache (EPH) and chronic primary headache (CPH) of RCS patients who participated in OHBRCS were studied according to their DMFT score in comparison to nonprimary headache patients. Demographic characteristics and risk factors were compared in different groups. We used crude and multiple logistic regression analyses in this study.

Results

The missing teeth were significantly higher in the CPH group than in the no CPH group (P < 0.001), and filled teeth were significantly higher in the EPH group than in the no EPH group (P < 0.001). In the crude model, there was a direct significant association between the prevalence of EPH and filled teeth total and > 5 filled teeth, and after adjusting for confounders, this relationship remained significant. The odds ratios of CPH were not associated with DMFT or its components in the adjusted models.

Conclusion

Our study found a correlation between filled teeth and EPH cases, but no correlation between CPH and DMFT or its components.
A new practical approach using TeamSTEPPS strategies and tools: – an educational design
Authors: Khoshnoodifar Mehrnoosh , Emadi Navaz , Mosalanejad Leili , Maghsoodzadeh Sara , Shokrpour Nasrin
Published: January 2024

Background

Teamwork has played a critical role in ensuring patients’ safety and preventing human errors in surgery. With advancements in educational technologies, including virtual reality, it is necessary to develop new teaching methods for interpersonal teamwork based on local needs assessments in countries with indigenous cultures. This study aimed to design and develop a new method of teaching teamwork in cesarean section surgery using virtual reality; we further evaluated the effects of this method on healthcare professionals’ knowledge and attitudes about teamwork.

Methods

This study was designed using the ADDIE instructional design model. The TeamSTEPPS Learning Benchmarks questionnaire was used to assess the educational needs of 85 participants who were members of the cesarean section surgery team. A specialized panel analyzed the extracted needs, and the scenario was compiled during the design stage. Finally, four virtual reality contents were created using 360-video H.265 format, which were prepared from specified scenarios in the development of the educational program. The TeamSTEPPS Learning Benchmarks questionnaire was used to measure knowledge, and the T-TAQ was used to measure the participants’ attitudes.

Results

Six micro- skills were identified as training needs, including briefing, debriefing, cross-monitoring, I'M SAFE checklist, call-out and check-back, and two-challenge rule. Intervention results showed that the virtual reality content improved teamwork competencies in an interprofessional team performing cesarean section surgery. A significant increase was observed in the mean score of knowledge and attitude after the intervention.

Conclusion

Through addressing the need for teamwork training, utilizing the TeamSTEPPS strategy, and incorporating new educational technologies like virtual reality, the collaboration among surgical team members can be enhanced.
Blended teaching mode based on small private online course and case-based learning in analgesia and sedation education in China: a comparison with an offline mode
Authors: Li Shu , Su Longxiang , Lou Ran , Liu Ying , Zhang Hua , Jiang Li ,   on behalf of the Chinese Analgesia and Sedation Education and Research (CASER) group
Published: January 2024

Background

Standardized training for pain, agitation-sedation, and delirium (PAD) management is urgently needed for Chinese intensivists’ continuing education. Since 2020, because of the COVID-19 pandemic, the Chinese Analgesia and Sedation Education and Research (CASER) group has used an online blended teaching mode based on a small private online course (SPOC) and case-based learning (CBL). This study evaluated whether an online blended teaching mode has similar effects on PAD management training when an offline mode cannot be used.

Materials and methods

Since 2020, the CASER group has provided offline training and online SPOC&CBL training three times each, targeting intensivists and ICU nurses in China. All participants were divided into an offline group and SPOC&CBL group. A final examination was offered in each training session to assess the students' mastery of professional knowledge. Teachers’ and students’ perceptions regarding the online SPOC&CBL mode were evaluated through questionnaires.

Results

Of all participants (n = 117), 106 completed all examinations and questionnaires. Most participants were aged 31–40 years (53, 50.0%), had an academic degree (60, 56.6%), and worked in a tertiary hospital (100, 94.34%). We assessed the learning effect on participants from two aspects: theory and clinical practice. There was no significant difference between the SPOC&CBL and offline groups in terms of theoretical, case analysis, and total scores (p > 0.05). In terms of the participants’ perceptions regarding the SPOC&CBL mode, 91.5% considered the online mode to be a useful and accessible alternative to improve knowledge and skills. A total of 95.7% of the participants believed that they could interact well with group members, and 87.2% believed that they had a good degree of participation. Of these participants, 76.6% believed that they had received valuable learning resources. All instructors believed that the SPOC&CBL mode was more flexible than the offline mode in terms of teaching time and location, and they were all willing to carry out training with the SPOC&CBL mode.

Conclusion

Compared to the offline mode, the SPOC&CBL mode can also enhance participants’ knowledge and skills and meets their expectations. Therefore, an online mode can be considered a potential method in PAD management education in China.
Revision total knee replacement finances: a detailed cost-analysis of operative practice at a regional tertiary referral centre
Authors: Alexiadis Aris , Reynolds Patrick , Al-Mouazzen Louay , Toms Andrew , Phillips John , Waterson Ben
Published: January 2024

Background

The revision knee complexity classification (RKCC) stratifies knee revision operations depending on their level of complexity from simple revisions (R1) to highly complex cases (R3). Current financial codes used for calculation of reimbursement for knee revision services provided at the Trust, rely on patients’ comorbidities. However, previous research has demonstrated that this approach may not yield an accurate financial account of knee revision arthroplasty cost. This is a single centre study from a secondary and tertiary revision unit, with work previously presented by the authors demonstrating that the majority of complex revision knee replacement within the region, take place in this unit. The aims of this study were to illustrate the current cost profile and renumeration service currently in place for revision knee and show the differences in cost based on complexity of the operation.

Methods

In this retrospective study, 90 cases who underwent revision knee operations in 2019 were analysed. Data was obtained from a tertiary referral centre where the episodes had occurred. Mean cost, tariff, and subsequent deficit were calculated for the R1, R2 and R3 episodes.

Results

R2 and R3 episodes were significantly more expensive than R1 episodes. The increase in cost between R3 and R2 episodes was not significant. The total cost of the revision operations was £1,162,343. Tariffs received for R2 and R3 revision operations were significantly more expensive than R1 operations. However, the increase in tariffs received for R3 operations was not significant in relation to R2 operations. The total amount of tariffs received by the Trust was £ 770,996 generating a net deficit of - £ 391,347.

Conclusion

Current financial coding for revision knee does not accurately predict costs associated with revision knee surgery. Net deficit varies depending on the RKCC grade of the knee revision episode with more complex operations resulting in a higher mean net deficit. Implementation of the RKCC could prove to be a useful tool in generating an accurate prediction of the cost associated with knee revision surgery.
Access to automated comparative feedback reports in primary care – a study of intensity of use and relationship with clinical performance among Swedish primary care practices
Authors: Anell Anders , Arvidsson Eva , Dackehag Margareta , Ellegård Lina Maria , Glenngård Anna Häger
Published: January 2024

Background

Digital applications that automatically extract information from electronic medical records and provide comparative visualizations of the data in the form of quality indicators to primary care practices may facilitate local quality improvement (QI). A necessary condition for such QI to work is that practices actively access the data. The purpose of this study was to explore the use of an application that visualizes quality indicators in Swedish primary care, developed by a profession-led QI initiative (“Primärvårdskvalitet”). We also describe the characteristics of practices that used the application more or less extensively, and the relationships between the intensity of use and changes in selected performance indicators.

Methods

We studied longitudinal data on 122 primary care practices’ visits to pages (page views) in the application over a period up to 5 years. We compared high and low users, classified by the average number of monthly page views, with respect to practice and patient characteristics as well as baseline measurements of a subset of the performance indicators. We estimated linear associations between visits to pages with diabetes-related indicators and the change in measurements of selected diabetes indicators over 1.5 years.

Results

Less than half of all practices accessed the data in a given month, although most practices accessed the data during at least one third of the observed months. High and low users were similar in terms of most studied characteristics. We found statistically significant positive associations between use of the diabetes indicators and changes in measurements of three diabetes indicators.

Conclusions

Although most practices in this study indicated an interest in the automated feedback reports, the intensity of use can be described as varying and on average limited. The positive associations between the use and changes in performance suggest that policymakers should increase their support of practices’ QI efforts. Such support may include providing a formalized structure for peer group discussions of data, facilitating both understanding of the data and possible action points to improve performance, while maintaining a profession-led use of applications.
Cost and availability of selected medicines after implementation of increased import verification fees
Authors: Ndagije Helen Byomire , Kesi Diana Nakitto , Rajab Kalidi , Onen Solomon , Serwanga Allan , Manirakiza Leonard , Ampaire Sheila , Mutasaaga Joseph , Mwesigwa Denis , Nahamya David
Published: January 2024

Background

Uganda imports approximately 90% of its medicines, with about 60% being distributed by the private sector. To discourage importation and promote local production of 37 selected locally manufactured medicines, the Ugandan government through the Ministry of Health in 2017 increased the import verification fees from 2 to 12%. The increase in verification fees ultimately affects cost and availability of these medicines. This study aimed to assess the cost and availability of the selected essential medicines after the 12% increase in verification fees in Uganda.

Methods

A cross sectional study among 328 wholesale and retail pharmacies and seven key informant interviews was conducted using a pretested data collection checklist and in-depth interview guide from February to September 2021 in Uganda. Data on the availability and prices of the medicines before (2017) and after (2020) the increase in verification fees was collected. Paired sample T-Test was used to test if there is a significant difference in prices before and after the 12% increase in verification fees.

Results

Mean availability of imported medicines was higher (54.8%, CI: 49.3–60.4) than the locally produced medicines (37.1%, CI: 31.9–42.7) except for locally manufactured parenteral preparations (54.6.%, CI: 49.1–60.1). Availability of locally produced medicines was mainly low (45%) while the imported medicines were fairly high (74%). Most commonly available locally manufactured medicines were Surgical spirit (89.9%), ORS (86%), Dextrose 5% solution (74.4%), Paracetamol 500 mg Tablets (73.8%) and Sodium Chloride 0.9% solution (72.9%). Most commonly available imported medicines were; Omeprazole 20 mg (94.2%), Amoxicillin Trihydrate 125 mg/5 ml (92.4%), Ciprofloxacin 500 mg (91.4%), Paracetamol Suspension 120 mg/5 ml (91.5%) and Metronidazole 200 mg Tablets (88.1%). Increase in lowest-priced local and imported medicines was significant for 10 (23.8%) and 7 (15.9%) of the medicines respectively. The median prices of imported medicines were generally higher than locally produced medicines. The median unit prices of 12 (28.6%) locally produced medicines and 20 (47.6%) imported medicines were higher than the international median unit prices.

Conclusions

The overall availability of imported medicines was still higher than the local medicines. The median prices of local and imported medicines generally increased or remained the same after the introduction of import verification fees. There is a need for price controls and transparency in the private sector.
Factors associated with work ability among employees of an Italian university hospital
Authors: Casolari Loretta , Curzi Ylenia , Mastroberardino Michele , Pistoresi Barbara , Poma Erica , Broccoli Lorenzo , Fabbri Tommaso
Published: January 2024

Background

A growing body of evidence clearly documents the benefits of integrated systems approaches to protecting and promoting the safety, health and well-being of workers. The purpose of this study is to provide a holistic view of the work ability of employees of an Italian University Hospital measuring their resources in relation to job demands. In particular, it examines socio-demographics, family and organizational antecedents of health professionals’ work ability.

Methods

A survey was conducted to assess the work ability of healthcare professionals, including physicians, nurses and administrative staff, working at the University Hospital of Modena (Italy). The data collection allows us to get a sample of 443 workers, who correspond to 11% of the target population. The data were analyzed using preliminary statistics on the main characteristics of the sample in terms of work ability, socio-demographic variables, family and organizational characteristics. In addition, logit models of the likelihood of having high work ability were estimated using SPSS version 25.

Results

Work ability decreases with increasing age, comorbidity, high body mass index, having at least one child under 5 and/or a dependent adult, having a poor work-life balance, and doing more than 20 h of housework. Specific job resources can significantly promote work ability, including relationship-oriented leadership, autonomy in decision making and individuals’ skill match. The nursing profession is associated with a low work ability. Finally, a significant gender gap has been documented. Women find it more difficult to reconcile life and work, especially when they have children of preschool age and work in professions with greater responsibilities, as in the case of women doctors, who experience lower work capacity.

Conclusions

Our results suggest that it is necessary to consider other factors, in addition to age, that are equally relevant in influencing work ability. Consequently, organisational interventions could be implemented to improve the work ability of all workers. In addition, we propose targeted interventions for groups at risk of reduced work capacity, in particular older workers (45 years and over), nurses, women with children of preschool age and in the position of physician.
Health care providers acceptance of default prescribing of TB preventive treatment for people living with HIV in Malawi: a qualitative study
Authors: De Groot L. M. , Shearer K. , Sambani C. , Kaonga E. , Nyirenda R. , Mbendera K. , Golub J. E. , Hoffmann C. J. , Mulder C.
Published: January 2024

Background

Tuberculosis (TB) preventive treatment (TPT) substantially reduces the risk of developing active TB for people living with HIV (PLHIV). We utilized a novel implementation strategy based on choice architecture (CAT) which makes TPT prescribing the default option. Through CAT, health care workers (HCWs) need to “opt-out” when choosing not to prescribe TPT to PLHIV. We assessed the prospective, concurrent, and retrospective acceptability of TPT prescribing among HCWs in Malawi who worked in clinics participating in a cluster randomized trial of the CAT intervention.

Methods

28 in-depth semi-structured interviews were conducted with HCWs from control (standard prescribing approach) and intervention (CAT approach) clinics. The CAT approach was facilitated in intervention clinics using a default prescribing module built into the point-of-care HIV Electronic Medical Record (EMR) system. An interview guide for the qualitative CAT assessment was developed based on the theoretical framework of acceptability and on the normalization process theory. Thematic analysis was used to code the data, using NVivo 12 software.

Results

We identified eight themes belonging to the three chronological constructs of acceptability. HCWs expressed no tension for changing the standard approach to TPT prescribing (prospective acceptability); however, those exposed to CAT described several advantages, including that it served as a reminder to prescribe TPT and routinized TPT prescribing (concurrent acceptability). Some felt that CAT may reduce HCW´s autonomy and might lead to inappropriate TPT prescribing (retrospective acceptability).

Conclusions

The default prescribing module for TPT has now been incorporated into the point-of-care EMR system nationally in Malawi. This seems to fit the acceptability of the HCWs. Moving forward, it is important to train HCWs on how the EMR can be leveraged to determine who is eligible for TPT and who is not, while acknowledging the autonomy of HCWs.
Cracking the code of health security: unveiling the balanced indices through rank-ordered effect analysis
Authors: Zhu Jianping , Wu Qi , Zhang Shiqi , Song Boliang , Wang Weiwei
Published: January 2024

Background

Health security is a critical issue which involves multiple dimensions. It has received increasing attention in recent years, especially in China. In order to improve the national health level, China has made many efforts, such as the “Healthy China 2030” plan proposed several years ago. However, due to the complexity of its national conditions and the difficulty of index design, the results of these efforts are not significant. Therefore, it is necessary to construct a new measurement index system.

Methods

Based on the questionnaire of “Health China 2030”, we have collected a total of 3,000 participants from all 31 provinces, autonomous regions, and municipalities in China. We used statistical methods such as multiple correspondence analysis and rank-ordered effect analysis to process the data. The balance index is constructed by a series of actions such as weight division, order calculation and ranking.

Results

Through multiple correspondence analysis, we can find that there was a close relation in the correspondence space between the satisfaction degrees 1, 2, and 3, while a far distance from satisfaction degrees 4 and 5. There were four positive and four negative indices separately based on the average expected level and four clusters after ordinal rank cluster analysis. Generally speaking, there are no prominent discrepancies across gender and residential areas.

Conclusions

We created and examined balanced indicators for health security in China based on the “Health China 2030” questionnaire. The findings of this study give insight into the overall situation of health security in China and indicate opportunities for improvement.
An exploration of relocation initiatives deployed within and between nursing homes: a qualitative study
Authors: Broekharst Damien S. E. , Stoop Annerieke , Achterberg Wilco P. , Caljouw Monique A. A. ,   on behalf of the RELOCARE Consortium, Luijkx Katrien G. , Verbeek Hilde , Hamers Jan P. H. , Schols Jos M. G. A. , de Boer Bram , Urlings Judith H. J. , Brouwers Mara , Landeweer Elleke G. M. , Luijendijk Dika H. J. , Schreuder Miranda C. , Zuidema Sytse U. , Perry Marieke , Koopmans Raymond T. C. M. , Groen Wim G.
Published: January 2024

Background

Relocations within and between nursing homes often induce stress, anxiety, and depression in residents and cause additional workload for and burnout in staff. To prevent this, many nursing homes deploy pre-transition initiatives, bridging initiatives, and post-transition initiatives to support residents and staff during the relocation process. As little is known about these initiatives, this study aims to explore the pre-relocation, bridging and post-relocation initiatives used for relocations within and between nursing homes.

Methods

In seven Dutch nursing homes, eight focus groups were conducted with two to six participants (N = 37) who were actively involved in relocation processes in different roles (i.e., managers, healthcare professionals, support staff, client council members, residents and family). The focus groups were conducted based on a predefined topic list and lasted approximately 60 min. The transcripts were recorded, transcribed verbatim and analysed using thematic coding.

Results

Nursing homes had to be inventive in developing relocation initiatives as neither shared guidelines nor knowledge exchange on this topic were available. A total of thirty-seven relocation initiatives were identified in these seven nursing homes. Nineteen pre-relocation initiatives were identified, of which eight emphasized information and engagement, three highlighted training and practice and eight stressed orientation and visualization. Seven bridging initiatives were identified, of which four emphasized coordination and continuity and three highlighted entertainment and celebration. Eleven post-relocation initiatives were identified, of which seven emphasized evaluation and troubleshooting and four highlighted change and adjustment.

Conclusion

The identified relocation initiatives were developed unassisted by nursing homes, due to a lack of shared guidelines, knowledge exchange and mutual learning on this topic. Therefore, it may be expedient and more effective to develop general guidelines for relocations within and between nursing homes in collaboration with nursing homes.
Predictors of extubation failure and prolonged mechanical ventilation among patients with intracerebral hemorrhage after surgery
Authors: Ho Ue-Cheung , Hsieh Chia-Jung , Lu Hsueh-Yi , Huang Abel Po-Hao , Kuo Lu-Ting
Published: January 2024

Background

Spontaneous intracerebral hemorrhage (ICH) is a condition associated with high mortality and morbidity. Survivors may require prolonged intubation with mechanical ventilation (MV). The aim of this study was to analyze the predictors of extubation failure and prolonged MV in patients who undergo surgical evacuation.

Methods

This retrospective study was conducted on adult patients with ICH who underwent MV for at least 48 h and survived > 14 days after surgery. The demographics, clinical characteristics, laboratory tests, and Glasgow Coma Scale score were analyzed.

Results

A total of 134 patients with ICH were included in the study. The average age of the patients was 60.34 ± 15.59 years, and 79.9% (n = 107) were extubated after satisfying the weaning parameters. Extubation failure occurred in 11.2% (n = 12) and prolonged MV in 48.5% (n = 65) patients. Multivariable regression analysis revealed that a white blood cell count > 10,000/mm3 at the time of extubation was an independent predictor of reintubation. Meanwhile, age and initial Glasgow Coma Scale scores were predictors of prolonged MV.

Conclusions

This study provided the first comprehensive characterization and analysis of the predictors of extubation failure and prolonged MV in patients with ICH after surgery. Knowledge of potential predictors is essential to improve the strategies for early initiation of adequate treatment and prognosis assessment in the early stages of the disease.
Oscillometry for personalizing continuous distending pressure maneuvers: an observational study in extremely preterm infants
Authors: Veneroni Chiara , Dellacà Raffaele L. , Küng Erik , Bonomi Beatrice , Berger Angelika , Werther Tobias
Published: January 2024

Rationale

Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values.

Objectives

In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization.

Methods

In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs).

Results

We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1–23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH2O). However, CDPXrs were equal to CDPOpt_SpO2 in only 6 infants, greater than CDPOpt_SpO2 in 10, and lower in 24 infants.

Conclusions

The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.
High-dose vitamin D3 supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections
Authors: Wall-Gremstrup Gustav , Holt Rune , Yahyavi Sam Kafai , Jorsal Mads Joon , Juul Anders , Jørgensen Niels , Blomberg Jensen Martin
Published: January 2024

Background

Vitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D3 supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs.

Methods

A double-blinded, randomized, placebo-controlled clinical trial of 307 infertile men with multiple secondary immunological endpoints. The vitamin D3 group (n = 151) initially received 300,000 IU (7,500 µg) cholecalciferol once - followed by 1,400 IU (35 µg) daily for 150 days. The placebo group (n = 156) did not receive active ingredients.

Results

At baseline, stratification into clinically relevant groups of vitamin D status (< 25; 25–50; 50–75; >75 nmol/L), showed an inverse association with total leucocyte concentrations (7.0 vs. 6.0 vs. 6.0 vs. 5.5 (109/L); p = 0.007), lymphocytes (2.4 vs. 2.1 vs. 2.0 vs. 2.0 (109/L); p = 0.048), CRP (2.0 vs. 1.7 vs. 1.2 vs. 1.2 (mg/L); p = 0.037), and orosomucoid (0.82 vs. 0.77 vs. 0.76 vs. 0.70 (g/L); p = 0.015). After 150 days, no differences were detected in WBC counts or APRs between the vitamin D3 and the placebo group. However, vitamin D3 treated men had a higher prevalence of self-reported RTIs compared with the placebo group (55% vs. 39%; p = 0.005).

Conclusions

High-dose vitamin D3 supplementation did not alter WBCs or APRs, but a higher prevalence of respiratory infections was observed in the vitamin D3 group. Serum 25(OH)D3 was negatively correlated with most WBCs, indicating that vitamin D status may be linked with inflammation and WBC turnover, but not an important determinant of developing RTIs.

Trial registration

NCT01304927 (ClinicalTrials.gov). Registered February 20, 2011.
MIF contribution to progressive brain diseases
Authors: Matejuk Agata , Benedek Gil , Bucala Richard , Matejuk Szymon , Offner Halina , Vandenbark Arthur A.
Published: January 2024

Progressive brain diseases create a huge social and economic burden on modern societies as a major cause of disability and death. Incidence of brain diseases has a significantly increasing trend and merits new therapeutic strategies. At the base of many progressive brain malfunctions is a process of unresolved, chronic inflammation. Macrophage migration inhibitory factor, MIF, is an inflammatory mediator that recently gained interest of neuro-researchers due to its varied effects on the CNS such as participation of nervous system development, neuroendocrine functions, and modulation of neuroinflammation. MIF appears to be a candidate as a new biomarker and target of novel therapeutics against numerous neurologic diseases ranging from cancer, autoimmune diseases, vascular diseases, neurodegenerative pathology to psychiatric disorders. In this review, we will focus on MIF’s crucial role in neurological diseases such as multiple sclerosis (MS), Alzheimer’s disease (AD) and glioblastoma (GBM).
Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model
Authors: Hao Yue , Su Yinchun , He Yifan , Zhang Wenyuan , Liu Yang , Guo Yu , Chen Xingfan , Liu Chunhan , Han Siyu , Wang Buyi , Liu Yushuang , Zhao Wei , Mu Lili , Wang Jinghua , Peng Haisheng , Han Junwei , Kong Qingfei
Published: January 2024

Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood–brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/β-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain–blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/β-catenin pathway.

Graphical Abstract
Autoimmune demyelination alters hypothalamic transcriptome and endocrine function
Authors: Carver Jonathan J. , Lau Kristy M. , Puckett Alexandra E. , Didonna Alessandro
Published: January 2024

The hypothalamus is a brain structure that is deputed to maintain organism homeostasis by regulating autonomic function and hormonal production as part of the neuroendocrine system. Dysfunction in hypothalamic activity results in behavioral alterations, depression, metabolic syndromes, fatigue, and infertility. Remarkably, many of these symptoms are associated with multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS) characterized by focal demyelination, immune cell infiltration into the brain parenchyma, and neurodegeneration. Furthermore, altered hormonal levels have been documented in MS patients, suggesting the putative involvement of hypothalamic deficits in MS clinical manifestations. Yet, a systematic analysis of hypothalamic function in response to neuroinflammatory stress is still lacking. To fill this gap, here we performed a longitudinal profiling of the hypothalamic transcriptome upon experimental autoimmune encephalomyelitis (EAE)—a murine disease model recapitulating key MS phenotypes at both histopathological and molecular levels. We show that changes in gene expression connected with an anti-inflammatory response start already at pre-onset and persist along EAE progression. Altered levels of hypothalamic neuropeptides were also detected, which possibly underlie homeostatic responses to stress and aberrant feeding behaviors. Last, a thorough investigation of the principal endocrine glands highlighted defects in the main steroidogenic pathways upon disease. Collectively, our findings corroborate the central role of hypothalamic dysfunction in CNS autoimmunity.
Mixed infection of ITPase-encoding potyvirid and secovirid in Mercurialis perennis: evidences for a convergent euphorbia-specific viral counterstrike
Authors: Mahillon Mathieu , Brodard Justine , Dubuis Nathalie , Gugerli Paul , Blouin Arnaud G. , Schumpp Olivier
Published: January 2024

Background

In cellular organisms, inosine triphosphate pyrophosphatases (ITPases) prevent the incorporation of mutagenic deaminated purines into nucleic acids. These enzymes have also been detected in the genomes of several plant RNA viruses infecting two euphorbia species. In particular, two ipomoviruses produce replicase-associated ITPases to cope with high concentration of non-canonical nucleotides found in cassava tissues.

Method

Using high-throughput RNA sequencing on the wild euphorbia species Mercurialis perennis, two new members of the families Potyviridae and Secoviridae were identified. Both viruses encode for a putative ITPase, and were found in mixed infection with a new partitivirid. Following biological and genomic characterization of these viruses, the origin and function of the phytoviral ITPases were investigated.

Results

While the potyvirid was shown to be pathogenic, the secovirid and partitivirid could not be transmitted. The secovirid was found belonging to a proposed new Comovirinae genus tentatively named "Mercomovirus", which also accommodates other viruses identified through transcriptome mining, and for which an asymptomatic pollen-associated lifestyle is suspected. Homology and phylogenetic analyses inferred that the ITPases encoded by the potyvirid and secovirid were likely acquired through independent horizontal gene transfer events, forming lineages distinct from the enzymes found in cassava ipomoviruses. Possible origins from cellular organisms are discussed for these proteins. In parallel, the endogenous ITPase of M. perennis was predicted to encode for a C-terminal nuclear localization signal, which appears to be conserved among the ITPases of euphorbias but absent in other plant families. This subcellular localization is in line with the idea that nucleic acids remain protected in the nucleus, while deaminated nucleotides accumulate in the cytoplasm where they act as antiviral molecules.

Conclusion

Three new RNA viruses infecting M. perennis are described, two of which encoding for ITPases. These enzymes have distinct origins, and are likely required by viruses to circumvent high level of cytoplasmic non-canonical nucleotides. This putative plant defense mechanism has emerged early in the evolution of euphorbias, and seems to specifically target certain groups of RNA viruses infecting perennial hosts.

Graphical Abstract
Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice
Authors: Tong Xiao J. , Akdemir Gokhan , Wadhwa Meetu , Verkman Alan S. , Smith Alex J.
Published: January 2024

It has been proposed that cerebrospinal fluid (CSF) can enter and leave the retina and optic nerve along perivascular spaces surrounding the central retinal vessels as part of an aquaporin-4 (AQP4) dependent ocular ‘glymphatic’ system. Here, we injected fluorescent dextrans and antibodies into the CSF of mice at the cisterna magna and measured their distribution in the optic nerve and retina. We found that uptake of dextrans in the perivascular spaces and parenchyma of the optic nerve is highly sensitive to the cisternal injection rate, where high injection rates, in which dextran disperses fully in the sub-arachnoid space, led to uptake along the full length of the optic nerve. Accumulation of dextrans in the optic nerve did not differ significantly in wild-type and AQP4 knockout mice. Dextrans did not enter the retina, even when intracranial pressure was greatly increased over intraocular pressure. However, elevation of intraocular pressure reduced accumulation of fluorescent dextrans in the optic nerve head, and intravitreally injected dextrans left the retina via perivascular spaces surrounding the central retinal vessels. Human IgG distributed throughout the perivascular and parenchymal areas of the optic nerve to a similar extent as dextran following cisternal injection. However, uptake of a cisternally injected AQP4-IgG antibody, derived from a seropositive neuromyelitis optica spectrum disorder subject, was limited by AQP4 binding. We conclude that large molecules injected in the CSF can accumulate along the length of the optic nerve if they are fully dispersed in the optic nerve sub-arachnoid space but that they do not enter the retina.
Patterns of remission from alcohol dependence in the United Kingdom: results from an online panel general population survey
Authors: Cunningham John A. , Schell Christina , Walker Hollie , Godinho Alexandra
Published: January 2024

Background

Previous research has demonstrated that remissions from alcohol use disorders can occur without accessing treatment. The current study explored the prevalence of such untreated remissions in the UK and further, examined the extent to which people who resolved an alcohol use disorder regarded themselves as ever, or currently, being in recovery.

Methods

Participants were recruited using the Prolific online platform. Participants who met criteria for lifetime alcohol dependence (ICD-10) were asked about their drinking at its heaviest, use of treatment services, whether they identified as being in recovery, and their current alcohol consumption (to identify those who were abstinent or drinking in a moderate fashion).

Results

A total of 3,994 participants completed surveys to identify 166 participants with lifetime alcohol dependence who were currently abstinent (n = 67) or drinking in a moderate fashion (n = 99). Participants who were currently abstinent were more likely to have accessed treatment than those who were currently moderate drinkers (44.4% versus 16.0%; Fischer’s exact test = 0.001). Further, those who were abstinent were heavier drinkers prior to remission [Mean (SD) drinks per week = 53.6 (31.7) versus 29.1 (21.7); t-test = 5.6, 118.7 df, p < .001] and were more likely to have ever identified themselves as ‘in recovery’ (51.5% versus 18.9%; Fischer’s exact test = 0.001) than current moderate drinkers.

Conclusions

While participants with an abstinent remission were more likely than those currently drinking in a moderate fashion to have accessed treatment and to identify as being ‘in recovery,’ the majority of participants reduced their drinking without treatment (and did not regard themselves as in recovery).
Investigating the complexity of the double distance problems
Authors: Braga Marília D. V. , Brockmann Leonie R. , Klerx Katharina , Stoye Jens
Published: January 2024

Background

Two genomes $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
over the same set of gene families form a canonical pair when each of them has exactly one gene from each family. Denote by $$n_*$$

n

∗

the number of common families of $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
. Different distances of canonical genomes can be derived from a structure called breakpoint graph, which represents the relation between the two given genomes as a collection of cycles of even length and paths. Let $$c_i$$

c
i

and $$p_j$$

p
j

be respectively the numbers of cycles of length i and of paths of length j in the breakpoint graph of genomes $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
. Then, the breakpoint distance of $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
is equal to $$n_*-\left( c_2+\frac{p_0}{2}\right)$$

n

∗

-

c
2

+

p
0

2

. Similarly, when the considered rearrangements are those modeled by the double-cut-and-join (DCJ) operation, the rearrangement distance of $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
is $$n_*-\left( c+\frac{p_e }{2}\right)$$

n

∗

-

c
+

p
e

2

, where c is the total number of cycles and $$p_e$$

p
e

is the total number of paths of even length.

Motivation

The distance formulation is a basic unit for several other combinatorial problems related to genome evolution and ancestral reconstruction, such as median or double distance. Interestingly, both median and double distance problems can be solved in polynomial time for the breakpoint distance, while they are NP-hard for the rearrangement distance. One way of exploring the complexity space between these two extremes is to consider a $$\sigma _k$$

σ
k

distance, defined to be $$n_*-\left( c_2+c_4+\ldots +c_k+\frac{p_0+p_2+\ldots +p_{k-2}}{2}\right)$$

n

∗

-

c
2

+

c
4

+
…
+

c
k

+

p
0

+

p
2

+
…
+

p

k
-
2

2

, and increasingly investigate the complexities of median and double distance for the $$\sigma _4$$

σ
4

distance, then the $$\sigma _6$$

σ
6

distance, and so on.

Results

While for the median much effort was done in our and in other research groups but no progress was obtained even for the $$\sigma _4$$

σ
4

distance, for solving the double distance under $$\sigma _4$$

σ
4

and $$\sigma _6$$

σ
6

distances we could devise linear time algorithms, which we present here.