bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge regarding human papillomavirus and cervical cancer prevention among medical students from Chulalongkorn University in Thailand
Authors: Sukrong Monchada , Prapaisilp Peerapong , Juntamongkol Tunchanok , Siranart Noppachai , Phoolcharoen Natacha , Assavapokee Nicha , Sirisabya Nakarin , Santibenchakul Somsook
Published: February 2024

Background

Cervical cancer is one of the leading causes of death among women in Thailand. General practitioners, within their primary healthcare role, play a vital role in the cervical cancer screening program, as they are the healthcare professionals most easily accessible to the general population. This study aims to determine the level of knowledge of cervical cancer and human papillomavirus (HPV) infection, HPV vaccination, and cervical cancer screening among last-year medical students.

Methods

A cross-sectional study was conducted among sixth-year medical students using an electronic self-administered questionnaire. The two-part questionnaire comprised demographic data and 12 true/false questions that assessed knowledge regarding HPV infection, HPV vaccination, and cervical cancer screening recommendations. Pilot testing revealed a high Cronbach’s alpha and test–retest reliability coefficient.

Results

A 67% response rate was achieved. Among the 198 respondents, only one (0.5%) student correctly answered over 80% of the questions while most respondents (172, 71.7%) correctly answered less than 60% of the questions. Less than half of the respondents correctly identified crucial aspects such as the primary cause of cervical cancer, recommended vaccination age, cytology sensitivity compared to HPV testing, and the recommended screening frequency for average-risk women.

Conclusions

This study highlights a significant lack of comprehension among Thai medical students concerning HPV infection, vaccination, and cervical cancer screening guidelines. Encouraging educational enhancement, effective communication, and heightened awareness of these crucial topics within the medical school curriculum are imperative.
Weathered granites and soils harbour microbes with lanthanide-dependent methylotrophic enzymes
Authors: Voutsinos Marcos Y. , West-Roberts Jacob A. , Sachdeva Rohan , Moreau John W. , Banfield Jillian F.
Published: February 2024

Background

Prior to soil formation, phosphate liberated by rock weathering is often sequestered into highly insoluble lanthanide phosphate minerals. Dissolution of these minerals releases phosphate and lanthanides to the biosphere. Currently, the microorganisms involved in phosphate mineral dissolution and the role of lanthanides in microbial metabolism are poorly understood.

Results

Although there have been many studies of soil microbiology, very little research has investigated microbiomes of weathered rock. Here, we sampled weathered granite and associated soil to identify the zones of lanthanide phosphate mineral solubilisation and genomically define the organisms implicated in lanthanide utilisation. We reconstructed 136 genomes from 11 bacterial phyla and found that gene clusters implicated in lanthanide-based metabolism of methanol (primarily xoxF3 and xoxF5) are surprisingly common in microbial communities in moderately weathered granite. Notably, xoxF3 systems were found in Verrucomicrobia for the first time, and in Acidobacteria, Gemmatimonadetes and Alphaproteobacteria. The xoxF-containing gene clusters are shared by diverse Acidobacteria and Gemmatimonadetes, and include conserved hypothetical proteins and transporters not associated with the few well studied xoxF systems. Given that siderophore-like molecules that strongly bind lanthanides may be required to solubilise lanthanide phosphates, it is notable that candidate metallophore biosynthesis systems were most prevalent in bacteria in moderately weathered rock, especially in Acidobacteria with lanthanide-based systems.

Conclusions

Phosphate mineral dissolution, putative metallophore production and lanthanide utilisation by enzymes involved in methanol oxidation linked to carbonic acid production co-occur in the zone of moderate granite weathering. In combination, these microbial processes likely accelerate the conversion of granitic rock to soil.
Osteomyelitis by Microsporum canis and Staphylococcus spp. in cat (Felis catus) – case report
Authors: Soares Fernanda O. , Rosado Isabel R. , Sousa Marcus V. C. , Dumont Carolyne F. , Bittar Joely F. F. , Martin Ian , Beletti Marcelo E. , Melo Roberta T. , Alves Endrigo G. L.
Published: February 2024

Background

Staphylococcus spp and Microsporum canis are zoonotic microorganisms which can cause infections and systemic diseases. The bone infection is usually caused by invasion of pathogen through the hematologic route. Mixed osteomyelitis caused by bacteria and fungi is rare, and to date, there have been no reports of mixed osteomyelitis with Staphylococcus spp. and Microsporum canis.

Case presentation

This essay reports an atypical presentation of mixed osteomyelitis (Staphylococcus spp. and Microsporum canis) in a domestic cat. A 15-month-old female Persian cat was presented to a veterinary service; the main complaint was the appearance of a nodule in the mandibular ventral rostral region. A radiographic exam performed on the animal showed proliferative and osteolytic bone lesions. The patient was submitted to a biopsy for histopathological evaluation, along with bacterial and fungal cultures. Results showed mixed osteomyelitis by Staphylococcus spp. and Microsporum canis. Microbial Sensitivity Test was performed to choose a more suitable treatment. Two surgical procedures were executed to resect and curette the lesion, and treatments with anti-inflammatory, antibiotic, and antifungal drugs were established, showing a positive clinical evolution. After 8 months of treatment, the patient’s owner moved to a different city, and the animal was seen by other veterinarians, who followed along with the same treatment. However, due to complications and a diminishing quality of life over 4 years of diagnosis, the patient was euthanized.

Conclusion

Given the above, mixed osteomyelitis is difficult to treat and can cause losses of life quality resulting death, especially in infections where M. canis is the agent causing the disease. Bacterial osteomyelitis is more frequently reported. But the lack of investigation of microorganisms other than bacteria, such as fungal cases, may imply in underdiagnosed cases. Treatment of osteomyelitis can be difficult considering the difficulties in isolating the pathological agent, resistance to the drug used, prolonged treatment time, and cost.
The effectiveness of simple heuristic features in sensor orientation and placement problems in human activity recognition using a single smartphone accelerometer
Authors: Barua Arnab , Jiang Xianta , Fuller Daniel
Published: February 2024

Background

Human activity Recognition (HAR) using smartphone sensors suffers from two major problems: sensor orientation and placement. Sensor orientation and sensor placement problems refer to the variation in sensor signal for a particular activity due to sensors’ altering orientation and placement. Extracting orientation and position invariant features from raw sensor signals is a simple solution for tackling these problems. Using few heuristic features rather than numerous time-domain and frequency-domain features offers more simplicity in this approach. The heuristic features are features which have very minimal effects of sensor orientation and placement. In this study, we evaluated the effectiveness of four simple heuristic features in solving the sensor orientation and placement problems using a 1D-CNN–LSTM model for a data set consisting of over 12 million samples.

Methods

We accumulated data from 42 participants for six common daily activities: Lying, Sitting, Walking, and Running at 3-Metabolic Equivalent of Tasks (METs), 5-METs and 7-METs from a single accelerometer sensor of a smartphone. We conducted our study for three smartphone positions: Pocket, Backpack and Hand. We extracted simple heuristic features from the accelerometer data and used them to train and test a 1D-CNN–LSTM model to evaluate their effectiveness in solving sensor orientation and placement problems.

Results

We performed intra-position and inter-position evaluations. In intra-position evaluation, we trained and tested the model using data from the same smartphone position, whereas, in inter-position evaluation, the training and test data was from different smartphone positions. For intra-position evaluation, we acquired 70–73% accuracy; for inter-position cases, the accuracies ranged between 59 and 69%. Moreover, we performed participant-specific and activity-specific analyses.

Conclusions

We found that the simple heuristic features are considerably effective in solving orientation problems. With further development, such as fusing the heuristic features with other methods that eliminate placement issues, we can also achieve a better result than the outcome we achieved using the heuristic features for the sensor placement problem. In addition, we found the heuristic features to be more effective in recognizing high-intensity activities.
Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study
Authors: Sun Cheng-Ming , Toulmonde Maud , Spalato-Ceruso Mariella , Peyraud Florent , Bessede Alban , Kind Michèle , Cousin Sophie , Buy Xavier , Palussiere Jean , Bougouin Antoine , Sautès-Fridman Catherine , Fridman Hervé Wolf , Pulido Marina , Italiano Antoine
Published: February 2024

Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin’s antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas. 50 patients participated: 20 in phase I and 30 in phase II. Changes in the TME were assessed in 28 patients using sequential tumor samples at baseline and day two of the cycle. Treatment notably decreased CD68 + CD163 + macrophages in biopsies from tumor lesions compared to pre-treatment samples in 9 of the 28 patients after 4 weeks. Baseline CD8 + T cell presence increased in 11 of these patients. In summary, up to 57% of patients exhibited a positive immunological response marked by reduced M2 macrophages or increased CD8 + T cells post-treatment. This positive shift in the TME correlated with improved clinical benefit and progression-free survival. This study offers the first prospective evidence of trabectedin’s immunological effect in advanced STS patients, highlighting a relationship between TME modulation and patient outcomes.

This study was registered with ClinicalTrial.gov, number NCT02406781.
Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice
Authors: Fu Yu , Zhang Yuan-lin , Liu Rong-qi , Xu Meng-meng , Xie Jun-ling , Zhang Xing-liao , Xie Guang-ming , Han Yao-ting , Zhang Xin-Min , Zhang Wan-ting , Zhang Jing , Zhang Jun
Published: February 2024

Background

The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear.

Results

The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis.

Conclusion

We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Graphical Abstract
Strategies for engaging older adults and informal caregivers in health policy development: A scoping review
Authors: Kolade Opeyemi Rashidat , Porat-Dahlerbruch Joshua , Makhmutov Rustem , van Achterberg Theo , Ellen Moriah Esther
Published: February 2024

Background

Care for older adults is high on the global policy agenda. Active involvement of older adults and their informal caregivers in policy-making can lead to cost–effective health and long-term care interventions. Yet, approaches for their involvement in health policy development have yet to be extensively explored. This review maps the literature on strategies for older adults (65+ years) and informal caregivers’ involvement in health policy development.

Method

As part of the European Union TRANS-SENIOR program, a scoping review was conducted using the Joanna Briggs Institute’s methodology. Published and grey literature was searched, and eligible studies were screened. Data were extracted from included studies and analysed using the Multidimensional Framework for Patient and Family Engagement in Health and Healthcare.

Results

A total of 13 engagement strategies were identified from 11 publications meeting the inclusion criteria. They were categorized as “traditional”, “deliberative” and “others”, adopting the World Bank’s categorization of engagement methods. Older adults and informal caregivers are often consulted to elicit opinions and identify priorities. However, their involvement in policy formulation, implementation and evaluation is unclear from the available literature. Findings indicate that older adults and their informal caregivers do not often have equal influence and shared leadership in policy-making.

Conclusion

Although approaches for involving older adults and their informal caregivers’ involvement were synthesized from literature, we found next to no information about their involvement in policy formulation, implementation and evaluation. Findings will guide future research in addressing identified gaps and guide policy-makers in identifying and incorporating engagement strategies to support evidence-informed policy-making processes that can improve health outcomes for older adults/informal caregivers.
DeepRisk network: an AI-based tool for digital pathology signature and treatment responsiveness of gastric cancer using whole-slide images
Authors: Tian Mengxin , Yao Zhao , Zhou Yufu , Gan Qiangjun , Wang Leihao , Lu Hongwei , Wang Siyuan , Zhou Peng , Dai Zhiqiang , Zhang Sijia , Sun Yihong , Tang Zhaoqing , Yu Jinhua , Wang Xuefei
Published: February 2024

Background

Digital histopathology provides valuable information for clinical decision-making. We hypothesized that a deep risk network (DeepRisk) based on digital pathology signature (DPS) derived from whole-slide images could improve the prognostic value of the tumor, node, and metastasis (TNM) staging system and offer chemotherapeutic benefits for gastric cancer (GC).

Methods

DeepRisk is a multi-scale, attention-based learning model developed on 1120 GCs in the Zhongshan dataset and validated with two external datasets. Then, we assessed its association with prognosis and treatment response. The multi-omics analysis and multiplex Immunohistochemistry were conducted to evaluate the potential pathogenesis and spatial immune contexture underlying DPS.

Results

Multivariate analysis indicated that the DPS was an independent prognosticator with a better C-index (0.84 for overall survival and 0.71 for disease-free survival). Patients with low-DPS after neoadjuvant chemotherapy responded favorably to treatment. Spatial analysis indicated that exhausted immune clusters and increased infiltration of CD11b+CD11c+ immune cells were present at the invasive margin of high-DPS group. Multi-omics data from the Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) hint at the relevance of DPS to myeloid derived suppressor cells infiltration and immune suppression.

Conclusion

DeepRisk network is a reliable tool that enhances prognostic value of TNM staging and aid in precise treatment, providing insights into the underlying pathogenic mechanisms.
Expanding the reach of commercial cell therapies requires changes at medical centers
Authors: Stroncek David F. , Zhang Nan , Ren Jiaqiang , Somerville Rob , Dinh Anh
Published: February 2024

The clinical application of cell therapies is becoming increasingly important for the treatment of cancer, congenital immune deficiencies, and hemoglobinopathies. These therapies have been primarily manufactured and used at academic medical centers. However, cell therapies are now increasingly being produced in centralized manufacturing facilities and shipped to medical centers for administration. Typically, these cell therapies are produced from a patient’s own cells, which are the critical starting material. For these therapies to achieve their full potential, more medical centers must develop the infrastructure to collect, label, cryopreserve, test, and ship these cells to the centralized laboratories where these cell therapies are manufactured. Medical centers must also develop systems to receive, store, and infuse the finished cell therapy products. Since most cell therapies are cryopreserved for shipment and storage, medical centers using these therapies will require access to liquid nitrogen product storage tanks and develop procedures to thaw cell therapies. These services could be provided by the hospital pharmacy or transfusion service, but the latter is likely most appropriate. Another barrier to implementing these services is the variability among providers of these cell therapies in the processes related to handling cell therapies. The provision of these services by medical centers would be facilitated by establishing a national coordinating center and a network of apheresis centers to collect and cryopreserve the cells needed to begin the manufacturing process and cell therapy laboratories to store and issue the cells. In addition to organizing cell collections, the coordinating center could establish uniform practices for collecting, labeling, shipping, receiving, thawing, and infusing the cell therapy.
Exploring the interplay of gut microbiota, inflammation, and LDL-cholesterol: a multiomics Mendelian randomization analysis of their causal relationship in acute pancreatitis and non-alcoholic fatty liver disease
Authors: Yan Congzhi , Bao Jingxia , Jin Jinji
Published: February 2024

Background

Acute pancreatitis and non-alcoholic fatty liver disease are both serious diseases in the digestive system. The pathogenesis of both diseases is extremely complex closely and it related to gut microbiota, inflammation, and blood fat. There is a close relationship between gut microbiota and blood lipids.

Methods

In this study, we used three types of exposure: 412 gut microbiota, 731 inflammatory cells, and 91 inflammatory proteins (pqtls), with LDL-C as an intermediary and acute pancreatitis and non-alcoholic fatty liver disease as outcomes. We mainly used MR-IVW, co-localization analysis, and reverse MR analysis methods for analysis.

Results

7 gut microbiota, 21 inflammatory cells, and 3 inflammatory proteins can affect LDL-C levels. LDL-C is associated with acute pancreatitis and non-alcoholic fatty liver disease.

Conclusions

Three omics were used: 412 gut microbiota, 731 inflammatory cells, and 91 inflammatory proteins (pqtls). It explains the causal relationship between multiomics, LDL- cholesterol, acute pancreatitis, and non-alcoholic fatty liver disease.
The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central–peripheral system interaction
Authors: Zhang Haiyang , Liu Yuting , Xia Duojin , Jiang Mengda , Li Yinwei , Sun Jing , Guan Haixia , Zhu Ling , Song Xuefei , Wang Jue , Fan Xianqun , Zhou Huifang
Published: February 2024

Background

Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status.

Methods

This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters.

Results

When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups.

Conclusions

This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central–peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central–peripheral system interaction mechanisms involved in autoimmune diseases.
Three-dimensional computed tomography analysis of airway volume in growing class II patients treated with Frankel II appliance
Authors: Ahmed Marwa Jameel , Diar-Bakirly Samira , Deirs Nelson , Hassan Amar , Ghoneima Ahmed
Published: February 2024

Objective

The purpose of this retrospective study was to assess the airway volume changes associated with the use of Frankel appliance (FR II) in Class II malocclusion patients using three-dimensional cone beam computed tomography (3D CBCT) imaging.

Materials and methods

The sample consisted of 31 Class II malocclusion patients (mean age 9.24 ± 1.93 years old, 17 males (54.8%) and 14 females (45.2%)) treated with FR II appliance by the same orthodontist for an average of 9 months ± 20 days. CBCT images were taken before and after treatment and upper airway volume changes were measured using Dolphin 3D software version11.0 (Dolphin Imaging, Chatsworth, CA) and statistically compared.

Results

Airway volume of nasal cavity, nasopharynx, oropharynx, hypopharynx and the total airway volume significantly increased after the use of FR II appliance. In addition, significant increase was reported in maxillary base, inter-molar, inter-premolar and inter-canine width. Significant increase in soft tissue thickness was only recorded opposite to CV2.

Conclusion

The use of the FR II appliance in growing subjects with Class II malocclusion led to a significant increase in the upper airway volume in addition to the anticipated dental and skeletal transverse expansion effects.
Intraoperative femurofibular angle combined with tibiofibular angle measurement has fewer correction errors in open-wedge high tibial osteotomy
Authors: Zhao Chen , Zhang Bing , Liu Xuejiao , Li Bo , Bao Liang , Liu Cong , Fan Lihong
Published: February 2024

Aim

This study aimed to verify the accuracy of intraoperative femurofibular angle combined with tibiofibular angle (FFA–TFA) measurement and compare it with traditional alignment line methods in open-wedge high tibial osteotomy (OWHTO).

Methods

A total of 174 knees of 122 patients undergoing OWHTO and using an alignment line or FFA–TFA measurement as an index of optimal correction were included in this retrospective study. The intraoperative alignment line passed through the targeted weight-bearing line (WBL) of the tibial plateau in the alignment line group. The intraoperative FFA–TFA aligned to the preplanned FFA–TFA angle in the FFA–TFA group. WBL, FFA, TFA, and knee joint-line convergence angle of the femur and tibia were assessed as radiological results preoperatively and one year after surgery. The Knee Society Score and the Western Ontario and McMaster Universities were assessed as objective clinical results.

Results

Postoperative WBL in the FFA–TFA group was closer to the target WBL than in the alignment line group (FFA–TFA vs alignment line group: 1.43 ± 1.20% vs 3.82 ± 3.29%; P < 0.001). The FFA–TFA group had fewer over-correction and under-correction rates than the alignment line group (28.7% and 12.6% vs 11.5% and 3.40%; P < 0.001). No significant differences were observed in the clinical results between the two groups one year after surgery (P > 0.05).

Conclusions

The intraoperative measurement of FFA–TFA had fewer complications in terms of under-correction and over-correction compared with the alignment line measurement. No significant differences between the two methods were observed in clinical results one year after surgery.
Moderating effect of work fatigue on the association between resilience and posttraumatic stress symptoms: a cross-sectional multi-country study among pharmacists during the COVID-19 pandemic
Authors: Younes Samar , Hallit Souheil , Mohammed Irfan , El Khatib Sarah , Brytek-Matera Anna , Eze Shadrach Chinecherem , Egwu Kenneth , Jabeen Rawshan , Pavlović Nebojša , Salameh Pascale , Cherfane Michelle , Akel Marwan , Haddad Chadia , Choueiry Randa , Fekih-Romdhane Feten , Iskandar Katia
Published: February 2024

Introduction

In the context of the COVID-19 pandemic, pharmacists, despite their vital contributions, have faced significant challenges that have impacted their mental well-being, potentially leading to the development of Post-Traumatic Stress symptoms (PTSS). The aim of this study was to investigate the role of work-related fatigue as a potential moderator in the relationship between pharmacists’ resilience and their likelihood of experiencing PTSS during the COVID-19 pandemic.

Methods

A cross-sectional survey was conducted online in eight countries from January to December 2021, including Brazil, Lebanon, Nigeria, Pakistan, Poland, Serbia, and Tunisia. The mediation analysis was conducted using PROCESS MACRO (an SPSS add-on) v3.4 model 1, taking work fatigue as a moderator in the association between resilience and PTSS.

Results

A total of 442 pharmacists were enrolled in this study (mean age = 33.91 ± 10.36 years) with 59.5% of them being females. The results were adjusted over country, gender, working in contact with COVID-19, working patients, working mandatory hours, working voluntary hours, age, household crowding index and number of months engaged in COVID-19. The interactions resilience by physical (Beta = 0.02; p = .029), mental (Beta = 0.02; p = .040) and emotional (Beta = 0.03; p = .008) work fatigue were significantly associated with PTSS; for pharmacists with low to moderate levels of physical (Beta = − 0.33; p < .001 and Beta = − 0.21; p = .001), mental (Beta = − 0.29; p < .001 and Beta = − 0.18; p = .006) and emotional (Beta = − 0.31; p < .001 and Beta = − 0.17; p = .008) work fatigue, higher resilience was significantly related to lower PTSS levels. However, for pharmacists with high levels of physical/mental/emotional work fatigue, the association between resilience and PTSS became non-significant.

Conclusion

This study highlights the complex relationship between work-related fatigue, resilience, and PTSS in pharmacists. It emphasizes the need to address work-related fatigue for pharmacists’ psychological well-being during crises, offering insights for tailored support and interventions.
Metformin versus metformin plus pioglitazone on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome: a single-center, open-labeled prospective randomized controlled trial
Authors: Zhao Han , Zhang Jiaqi , Xing Chuan , Cheng Xiangyi , He Bing
Published: February 2024

Objective

To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome (PCOS).

Methods

Sixty normal-weight women with PCOS were recruited between January and September 2022 at the Shengjing Hospital of China Medical University. They were randomly assigned to the MET or PIOMET groups for 12 weeks of MET monotherapy or PIOMET therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and the oral glucose insulin-releasing test (OGIRT) were performed at baseline and after the 12-week treatment.

Results

Thirty-six participants completed the trial. MET and PIOMET therapies improved menstrual cycles after the 4- and 12-week treatments; however, there was no statistical difference between the two groups. PIOMET therapy improved luteinizing hormone (LH), luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, and free androgen index (FAI) levels after the 4-week treatment, whereas MET monotherapy only improved total testosterone (TT) levels compared to baseline (P < 0.05). Both MET and PIOMET therapies improved TT and anti-Mullerian hormone (AMH) levels after the 12-week treatment (P < 0.05). In addition, only PIOMET therapy significantly improved sex hormone-binding globulin (SHBG), FAI, and androstenedione (AND) levels than the baseline (P < 0.05). PIOMET therapy improved SHBG and AMH levels more effectively than MET monotherapy (P < 0.05). Furthermore, PIOMET treatment was more effective in improving blood glucose levels at 120 and 180 min of OGIRT compared to MET monotherapy (P < 0.05).

Conclusions

In normal-weight women with PCOS, PIOMET treatment may have more benefits in improving SHBG, AMH, and postprandial glucose levels than MET monotherapy, and did not affect weight. However, the study findings need to be confirmed in PCOS study populations with larger sample sizes.
Arachidonic acid inhibit granulosa cell function by affecting metabolic function of liver in brown adipose transplantation rats
Authors: Yan Yan , Di Fangfang , Zhang Ruoxi , Song Liwen , Zhang Runjie , Qiu Jin
Published: February 2024

Background

Polycystic ovary syndrome (PCOS) is a gynecological endocrine disease and could be considered a metabolic disease because it is often accompanied by obesity and insulin resistance. Brown adipose tissue (BAT) transplantation has been shown to be effective in treating PCOS rats.

Results

The study demonstrated that BAT successfully recovered the reproductive and metabolic phenotype of PCOS rats. The disorder estrous cycle, abnormal hyperglycemia and the expression of liver factors were improved. Differentially expressed metabolites were analyzed, among them, arachidonic acid may play a role in inhibiting cell proliferation, enhancing oxidative stress reaction, promoting estrogen expression, and reducing progesterone level in KGN cells.

Conclusion

Our findings suggest that BAT transplantation may be a therapeutic strategy for PCOS by changing the expression of some cytokines and metabolites. Differentially expressed metabolites might be crucially important for the pathogenesis of PCOS.
Coexistence of a fluid responsive state and venous congestion signals in critically ill patients: a multicenter observational proof-of-concept study
Authors: Muñoz Felipe , Born Pablo , Bruna Mario , Ulloa Rodrigo , González Cecilia , Philp Valerie , Mondaca Roberto , Blanco Juan Pablo , Valenzuela Emilio Daniel , Retamal Jaime , Miralles Francisco , Wendel-Garcia Pedro D. , Ospina-Tascón Gustavo A. , Castro Ricardo , Rola Philippe , Bakker Jan , Hernández Glenn , Kattan Eduardo
Published: February 2024

Background

Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission.

Methods

Multicenter, prospective cross-sectional observational study conducted in three medical–surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected.

Results

Ninety patients were included. Median age was 63 [45–71] years old, and median SOFA score was 9 [7–11]. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR−). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR− groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals.

Conclusions

Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.
Human activities and densities shape insecticide resistance distribution and dynamics in the virus-vector Culex pipiens mosquitoes from Morocco
Authors: Arich Soukaina , Assaid Najlaa , Weill Mylène , Tmimi Fatim-Zohra , Taki Hassan , Sarih M’hammed , Labbé Pierrick
Published: February 2024

Background

Mosquitoes of the Culex pipiens complex are widely distributed vectors for several arboviruses affecting humans. Consequently, their populations have long been controlled using insecticides, in response to which different resistance mechanisms have been selected. Moreover, their ecological preferences and broad adaptability allow C. pipiens mosquitoes to breed in highly polluted water bodies where they are exposed to many residuals from anthropogenic activities. It has been observed for several mosquito species that anthropization (in particular urbanization and agricultural lands) can lead to increased exposure to insecticides and thus to increased resistance. The main objective of the present study was to investigate whether and how urbanization and/or agricultural lands had a similar impact on C. pipiens resistance to insecticides in Morocco.

Methods

Breeding sites were sampled along several transects in four regions around major Moroccan cities, following gradients of decreasing anthropization. The imprint of anthropogenic activities was evaluated around each site as the percentage of areas classified in three categories: urban, agricultural and natural. We then assessed the frequencies of four known resistance alleles in these samples and followed their dynamics in five urban breeding sites over 4 years.

Results

The distribution of resistance alleles revealed a strong impact of anthropization, in both agricultural and urbanized lands, although different between resistance mutations and between Moroccan regions; we did not find any clear trend in the dynamics of these resistance alleles during the survey.

Conclusions

Our study provides further evidence for the role of anthropic activities in the selection and maintenance of mutations selected for resistance to insecticides in mosquitoes. The consequences are worrying as this could decrease vector control capacities and thus result in epizootic and epidemic outbreaks. Consequently, concerted and integrated disease control strategies must be designed that include better management regarding the consequences of our activities.

Graphical Abstract
First molecular evidence of potential Culicoides vectors implicated in bluetongue virus transmission in Morocco
Authors: Daif Soukaina , El Berbri Ikhlass , Fassi Fihri Ouafaa
Published: February 2024

Background

Bluetongue is a non-contagious viral disease that affects both domestic and wild ruminants. It is transmitted primarily by small hematophagous Diptera belonging to the genus Culicoides (Diptera: Ceratopogonidae). The current study represents the first molecular investigation into the potential role of Culicoides imicola, Culicoides paolae, Culicoides newsteadi, Culicoides spp., and Culicoides circumscriptus as bluetongue virus (BTV) vectors in Morocco. Additionally, the study aimed to evaluate the vectorial activity of midges during the survey seasons.

Methods

Parous females of these species were captured from several regions of Morocco (6 out of 12) from 2018 to 2021 using Onderstepoort Veterinary Institute (OVI) traps. A total of 2003 parous female specimens were grouped into 55 batches. The midge body of each batch was dissected into three regions (head, thorax, and abdomen), and these regions were analyzed separately using reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Results

BTV RNA was detected in 45 out of the 55 batches tested, indicating a positivity rate of 81.8%. The RT-qPCR-positive pools of the studied Culicoides species exhibited high levels of BTV positivity in each body part (head, thorax, and abdomen), confirming the successful replication of the virus within midge bodies. The BTV circulation was substantial across all three survey seasons (spring, summer, and autumn). High infection rates, calculated using the minimum infection rate (MIR) and maximum likelihood estimation (MLE), were observed during the collection seasons, particularly in autumn and spring, and for all investigated Culicoides species, most notably for C. imicola and C. newsteadi. These increased infection rates underscore the significant risk of Culicoides transmitting the BTV in Morocco.

Conclusions

The detection of BTV positivity in Culicoides spp. (lacking wing spots that allow their differentiation according to morphological identification keys) suggested that other Culicoides species are competent for BTV transmission in Morocco. The study results indicated, for the first time at the molecular level, that C. imicola and C. newsteadi are the primary potential vectors of BTV in Morocco and that C. paolae and C. circumscriptus are strongly implicated in the propagation of bluetongue at the national level.

Graphical Abstract
Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis
Authors: Nimmo Camus , Ortiz Arturo Torres , Tan Cedric C. S. , Pang Juanita , Acman Mislav , Millard James , Padayatchi Nesri , Grant Alison D. , O’Donnell Max , Pym Alex , Brynildsrud Ola B. , Eldholm Vegard , Grandjean Louis , Didelot Xavier , Balloux François , van Dorp Lucy
Published: February 2024

Background

Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug.

Methods

We compiled a dataset of 3682 Mtb genomes, including 180 carrying variants in mmpR5, and its immediate background (i.e. mmpR5 promoter and adjacent mmpL5 gene), that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We characterised the occurrence of all nonsynonymous mutations in mmpR5 in this dataset and estimated, using time-resolved phylogenetic methods, the age of their emergence.

Results

We identified eight cases where RAVs were present in the genomes of strains collected prior to the use of bedaquiline in TB treatment regimes. Phylogenetic reconstruction points to multiple emergence events and circulation of RAVs in mmpR5, some estimated to predate the introduction of bedaquiline. However, epistatic interactions can complicate bedaquiline drug-susceptibility prediction from genetic sequence data. Indeed, in one clade, Ile67fs (a RAV when considered in isolation) was estimated to have emerged prior to the antibiotic era, together with a resistance reverting mmpL5 mutation.

Conclusions

The presence of a pre-existing reservoir of Mtb strains carrying bedaquiline RAVs prior to its clinical use augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control.
Targeting an inflammation-amplifying cell population can attenuate osteoarthritis-associated pain
Authors: Pandey Akshay , Singla Mamta , Geller Ana , Goodman Stuart B. , Bhutani Nidhi
Published: February 2024

Background

Understanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade.

Methods

In this study, we have tested the function of the cartilage-resident IL1R1+TNF-R2+ Inf-A cells in OA. We have identified that the IL1R1+TNF-R2+ Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice.

Results

Modulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants.

Conclusion

These studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling.
Different mechanisms underlie compulsive alcohol self-administration in male and female rats
Authors: Toivainen Sanne , Xu Li , Gobbo Francesco , Della Valle Andrea , Coppola Andrea , Heilig Markus , Domi Esi
Published: February 2024

Background

Sex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as continued use despite negative consequences (“compulsive use”). Studies in experimental animals can help provide an understanding of the role sex plays to influence these behaviors.

Methods

Large populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline (fixed ratio, unpunished) operant alcohol self-administration, motivation to self-administer alcohol (progressive ratio), and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety-like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study.

Results

Unpunished self-administration of alcohol did not differ between males and females when alcohol intake was corrected for body weight. Overall, females showed higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats when intermediate shock intensities were used (0.2 and 0.25 mA); at higher shock intensities, responding was uniformly suppressed in both males and females. We also found less steep discounting in females when alcohol was devalued by delaying its delivery. Males exhibited a stronger motivation to obtain alcohol under unpunished conditions, while females showed higher corticosterone levels at baseline. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor. We did not find differences in alcohol-related behaviors throughout the various stages of the estrous cycle.

Conclusions

Our results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction.