bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
Authors: Defois Anais , Bon Nina , Charpentier Alexandre , Georget Melina , Gaigeard Nicolas , Blanchard Frederic , Hamel Antoine , Waast Denis , Armengaud Jean , Renoult Ophelie , Pecqueur Claire , Maugars Yves , Boutet Marie-Astrid , Guicheux Jerome , Vinatier Claire 
Published: June 2023

Abstract
Background
Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes.

Methods
Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays.

Results
We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF.

Conclusion
These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis.
The tumor promoter cysteinyl leukotriene receptor 1 regulates PD-L1 expression in colon cancer cells via the Wnt/β-catenin signaling axis
Authors: Satapathy Shakti Ranjan , Ghatak Souvik , Sjölander Anita 
Published: June 2023

AbstractImmunotherapy targeting programmed death-ligand 1 (PD-L1) or PD-1 in solid tumors has been shown to be clinically beneficial. However, in colorectal cancer (CRC), only a subset of patients benefit from PD-1/PD-L1 treatment. Previously, we showed that high cysteinyl leukotriene receptor 1 (CysLT1R) levels are associated with poor prognosis in CRC patients. Recently, we have revealed the role of the tumor promoter CysLT1R in drug resistance and stemness in colon cancer (CC) cells. Here, we show the role of the CysLT1R/Wnt/β-catenin signaling axis in the regulation of PD-L1 using both in vitro and in vivo preclinical model systems. Interestingly, we found that both endogenous and IFNγ-induced PD-L1 expression in CC cells is mediated through upregulation of CysLT1R, which enhances Wnt/β-catenin signaling. Therapeutic targeting of CysLT1R with its antagonist montelukast (Mo), as well as CRISPR/Cas9-mediated or doxycycline-inducible functional absence of CysLT1R, negatively regulated PD-L1 expression in CC cells. Interestingly, an anti-PD-L1 neutralizing antibody exhibited stronger effects together with the CysLT1R antagonist in cells (Apcmut or CTNNB1mut) with either endogenous or IFNγ-induced PD-L1 expression. Additionally, mice treated with Mo showed depletion of PD-L1 mRNA and protein. Moreover, in CC cells with combined treatment of a Wnt inhibitor and an anti-PD-L1 antibody was effective only in β-catenin-dependent (APCmut) context. Finally, analysis of public dataset showed positive correlations between the PD-L1 and CysLT1R mRNA levels. These results elucidate a previously underappreciated CysLT1R/Wnt/β-catenin signaling pathway in the context of PD-L1 inhibition in CC, which might be considered for improving the efficacy of anti-PD-L1 therapy in CC patients.
Breastfeeding environment and experiences at the workplace among health workers in the Upper East Region of Ghana
Authors: Kubuga Clement Kubreziga , Tindana Juliana 
Published: June 2023

Abstract
Background
Employed mothers have lower rates of breastfeeding, including health workers who are supposed to be advocates for breastfeeding. These working mothers need a supportive workplace environment to breastfeed, yet Ghana’s breastfeeding policy neither mentions the workplace breastfeeding environment nor offers any information on it.

Methods
A convergent parallel mixed-methods design was used in this study to determine: facilities with a complete breastfeeding support environment (BFSE); breastfeeding challenges experienced; coping strategies and motivators for breastfeeding among health workers in the Upper East Region of Ghana; and Management’s awareness of the need for an institutional breastfeeding support policy. Quantitative and qualitative data were analyzed using descriptive statistics and thematic analysis respectively. The research was conducted from January to April 2020.

Results
All facilities (39) had incomplete BFSE and management representatives of health facilities (39) did not have and were not aware that their respective facilities needed to have a specific workplace breastfeeding policy that fed into the national policy agenda. Breastfeeding challenges at workplaces included: lack of private space for breastfeeding; inadequate support from co-workers and management; emotional stress; and inadequate breastfeeding breaks and work options. Women adapted to these challenges by employing coping strategies such as: bringing children to work with / without caretakers; leaving children at home; seeking support from co-workers and family members; feeding children with supplementary foods; adding annual leave to maternity leave; breastfeeding in cars / offices; and sending children to daycare. Interestingly, the women were still motivated to breastfeed. Health benefits of breastmilk, the convenience and readily available nature of breastmilk, moral obligation to breastfeed, and cheap cost of breastmilk emerged as key motivators to breastfeed.

Conclusion
Our findings suggest that health workers have poor BFSE and are faced with numerous breastfeeding challenges. There is a need for programs that improve BFSE in health facilities.
Establishment and validation of a prognostic risk classification for patients with stage T1-3N0M0 esophageal squamous cell carcinoma
Authors: Huang Yang-Yu , Zheng Yan , Liang Shen-Hua , Wu Lei-Lei , Liu Xuan , Xing Wen-Qun , Ma Guo-Wei 
Published: June 2023

Abstract
Introduction
At present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model.

Methods
Stage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)—who had undergone esophagectomy in 1995–2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses.

Results
The Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history − 0.012 × hemoglobin–0.042 × albumin − 0.032 × lymph nodes]. Patients were grouped into three classes—Class A (5.14–7.26, low risk), Class B (7.27–7.70, middle risk), and Class C (7.71–9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P < 0.001). Similar findings were observed in the validation group. Additionally, Cox regression analysis showed that Esorisk aggregate score remained significantly associated with CSS in the training cohort and validation cohort after adjusting for other confounders.

Conclusions
We combined the data of two large clinical centers, and comprehensively considered their valuable clinical factors and hematological indicators, established and verified a new prognostic risk classification that can predict CSS of stage T1-3N0M0 ESCC patients.
The challenges of international collaboration in conflict and health research: experience from the Research for Health in Conflict-Middle East and North Africa (R4HC-MENA) partnership
Authors: Lin Chiu-Yi , Meagher Kristen , Bricknell Martin , Patel Preeti , El Achi Nassim , Kutluk Tezer , Harding Richard , Kienzler Hanna , Giacaman Rita , Mukherji Deborah , Shamieh Omar , Sullivan Richard 
Published: June 2023

Abstract
Background
Healthcare is a basic human right extending across all humanitarian contexts, including conflict. Globally, two billion people are living under conditions of insecurity and violent armed conflict with a consequent impact on public health. Health research in conflict-affected regions has been recognised as important to gain more understanding of the actual needs of such populations, to optimise healthcare delivery, as well as to inform advocacy and policy change. International collaborative research maximises the resources and skills available for dealing with global health issues, builds capacity and endeavours to ensure the research reflects real needs of the populations. Under the UK’s Global Challenge Research Fund in 2017 a number of such international programs were created including the Research for Health in Conflict-Middle East and North Africa (R4HC-MENA) partnership to build capacity in conflict and health research as well as study specific areas, namely noncommunicable diseases in conflict (cancer & mental health) and the political economy of health in conflict.

Methods
A qualitative study using semi-structured online interviews was conducted to explore researchers’ and stakeholders’ perspectives on the R4HC-MENA programme over its lifetime from 2017 to 2021. It aimed to understand the factors that influenced and accelerated international collaboration within the R4HC-MENA programme on conflict and health research, and to provide deeper insights into the implementation of the programme. Data collection was conducted from March 2022 to June 2022. Purposive and snowball sampling techniques were used for participant recruitment. Thematic analysis was applied for data analysis.

Results
Twelve researchers/stakeholders participated in this study: four men and eight women. Four main themes were generated: Theme 1: Network building (personal and institutional levels); Theme 2: Hierarchies and power dynamics (power imbalance between different academic status, genders and institutions); Theme 3: Communication challenges; Theme 4: Career development (management, leadership, research, and teaching skills).

Conclusions
This study provided preliminary insights into perspectives on international collaboration in a major international programme of research on conflict and health. Several key challenges and outputs were generated by the researchers in this study. The findings are important for further developing effective strategies to tackle the challenge of power imbalance and ineffective communication in international research collaborations.
How do Italian pediatric endocrinologists approach gender incongruence?
Authors: Ciancia Silvia , Iughetti Lorenzo 
Published: June 2023

Abstract
Background
Gender incongruence (GI) is a term used to describe a marked and persistent incompatibility between the sex assigned at birth (SAAB) and the experienced gender. Some persons presenting with GI experience a severe psychological distress defined as gender dysphoria (GD).. Although the prevalence of GI is probably underestimated, recently a great increase in numbers of transgender and gender diverse (TGD) youths presenting at the gender clinics has been registered. After a careful multidisciplinary evaluation and upon acquisition of informed consent from the youth and the legal guardian(s), puberty suppression can be started in TGD youths, followed by the addition of gender affirming hormones (GAH) by the age of 16 years. Although Italian specific guidelines are available, their application is often complex because of (among other reasons) lack of specialized centers and healthcare professional with experience in the field and the regional differences within the Italian healthcare system.

Main body
To investigate the care offered to TGD youths across Italy, we proposed a survey of 20 questions to the directors of the 32 Italian Centers of pediatric endocrinology participating to the Study Group on Growth and Puberty of the Italian Society of Pediatric Endocrinology (ISPED). Eighteen pediatric endocrinologists representative of 16 different centers belonging to 11 different regions responded to the survey. In the large majority of centers TGD youths are taken in charge between the age of 12 and 18 years and at least three healthcare professional are involved. Most of Italian pediatric endocrinologists follow only a very limited number of TGD youths and reference centers for TGD youths are lacking.

Conclusion
There is an urgent need for gender clinics (homogeneously distributed on the national territory) where TGD youths can access high standard care.
Spatial distribution pattern across multiple microbial groups along an environmental stress gradient in tobacco soil
Authors: Li Pengfei , Xu Tianyang , Hu Qiulong , Gu Songsong , Yang Yishuai , Wang Zhengqiang , Deng Xiangdong , Wang Bin , Li Wei , Zhu Yanmei 
Published: June 2023

Abstract
Background
It has become commonplace to explore the spatial distribution patterns of microbial communities in natural ecosystems. However, few have looked at the responses of community diversity, structure, and assembly processes from different microbial groups to changes in environmental stress caused by altitude.

Purpose
We investigated the spatial and biogeographical patterns of different microbial groups, including bacteria, fungi, and protists, from tobacco soil along an altitudinal gradient to evaluate the influence of geographic distance and environmental stress on microbial distribution pattern.

Methods
DDR (distance decay relationship) model was calculated to evaluate the spatial distribution pattern. Then, NCM (neutral community model) and two null-modelling-based approaches, NST (normalized stochasticity ratio) and iCAMP (the infer community assembly mechanism by phylogenetic-bin-based null model analysis), were used to reveal the importance of stochastic and deterministic processes to microbial community assembly by utilizing high-throughput sequencing data.

Result
Bacterial community α-diversity decreased significantly (P < 0.05) with increasing environmental stress. Moreover, all communities exhibited a significant DDR pattern (P < 0.001), with the slope of bacteria (0.146) being significantly higher (P < 0.05) than that of fungi (0.059) and protists (0.060). The results of NCM and the two null-modelling-based approaches revealed the importance of stochastic processes to bacterial (83.4%) and protist (69.9%) communities, which were primarily shaped by drift and dispersal limitation, respectively; meanwhile, deterministic processes were important to the fungal community (53.7%). Additionally, we found a significant correlation between the assembly process and geographic distance (P < 0.05).

Conclusion
Our study provides a complementary perspective to the study of multiple hierarchical groups across different spatial scales (i.e., horizontal and vertical scales).

Graphical Abstract
Stereotactic ablative body radiation therapy for isolated pulmonary metastases from pancreatic cancer after metastectomy with positive margins: a case report
Authors: Alnsour Anoud , Le Hien , Byrne Adam , Rodgers Nick , Roos Daniel 
Published: June 2023

Abstract
Background
Isolated pulmonary oligometastases as the first site of dissemination after initial resection of pancreatic ductal adenocarcinoma (PC) is a rare event, and the treatment in this subgroup is challenging. Recurrence in the lung after initial primary tumour resection is associated with the most long-term survivors of patients with metastatic PC. Stereotactic ablative body radiation therapy (SABR) or metastectomy for pulmonary oligometastases from PC is becoming more common. However, patients with close or positive margins after metastectomy for isolated pulmonary metastatic PC are at high risk for recurrence. This requires a treatment capable of achieving high rates of local control and improved quality of life by delaying the need for systemic chemotherapy. In other settings, SABR has been shown to achieve these goals, allowing safe dose escalation with excellent conformity and short duration of treatment.

Case presentation
We report the case of a 48-year old Caucasian man with a history of locally advanced PC initially treated with neoadjuvant chemotherapy followed by Whipple’s resection in August 2016. After a disease-free interval of 3 years, he developed three isolated pulmonary metastases which were treated with local resection. In the setting of microscopically positive resection margins (R1), adjuvant lung SABR was delivered to all three sites. His treated lung disease remained radiologically stable for up to twenty months after SABR. Treatment was well tolerated. In January 2021, he developed a malignant pre-tracheal node which was treated with conventionally fractionated radiotherapy and remained controlled for the duration of follow-up. A year later, he developed widespread metastatic disease including pleura, bone and adrenal gland, together with presumed progression in one of the original lung lesions, receiving palliative radiotherapy for right chest wall pain. He was later found to have an intracranial metastasis and died in February 2022, 5½ years after initial treatment.

Conclusion
We present the case of a patient treated with SABR after R1 resection of 3 isolated pulmonary metastases from PC, with no treatment toxicities and durable local control. For well-selected patients in this setting, adjuvant lung SABR may be a safe and effective treatment option.
Bioactivity of human adult stem cells and functional relevance of stem cell-derived extracellular matrix in chondrogenesis
Authors: Jiang Yangzi , Tuan Rocky S. 
Published: June 2023

Abstract
Background
Autologous chondrocyte implantation (ACI) has been used to treat articular cartilage defects for over two decades. Adult stem cells have been proposed as a solution to inadequate donor cell numbers often encountered in ACI. Multipotent stem/progenitor cells isolated from adipose, bone marrow, and cartilage are the most promising cell therapy candidates. However, different essential growth factors are required to induce these tissue-specific stem cells to initiate chondrogenic differentiation and subsequent deposition of extracellular matrix (ECM) to form cartilage-like tissue. Upon transplantation into cartilage defects in vivo, the levels of growth factors in the host tissue are likely to be inadequate to support chondrogenesis of these cells in situ. The contribution of stem/progenitor cells to cartilage repair and the quality of ECM produced by the implanted cells required for cartilage repair remain largely unknown. Here, we evaluated the bioactivity and chondrogenic induction ability of the ECM produced by different adult stem cells.

Methods
Adult stem/progenitor cells were isolated from human adipose (hADSCs), bone marrow (hBMSCs), and articular cartilage (hCDPCs) and cultured for 14 days in monolayer in mesenchymal stromal cell (MSC)–ECM induction medium to allow matrix deposition and cell sheet formation. The cell sheets were then decellularized, and the protein composition of the decellularized ECM (dECM) was analyzed by BCA assay, SDS-PAGE, and immunoblotting for fibronectin (FN), collagen types I (COL1) and III (COL3). The chondrogenic induction ability of the dECM was examined by seeding undifferentiated hBMSCs onto the respective freeze-dried solid dECM followed by culturing in serum-free medium for 7 days. The expression levels of chondrogenic genes SOX9, COL2, AGN, and CD44 were analyzed by q-PCR.

Results
hADSCs, hBMSCs, and hCDPCs generated different ECM protein profiles and exhibited significantly different chondrogenic effects. hADSCs produced 20–60% more proteins than hBMSCs and hCDPCs and showed a fibrillar-like ECM pattern (FNhigh, COL1high). hCDPCs produced more COL3 and deposited less FN and COL1 than the other cell types. The dECM derived from hBMSCs and hCDPCs induced spontaneous chondrogenic gene expression in hBMSCs.

Conclusions
These findings provide new insights on application of adult stem cells and stem cell-derived ECM to enhance cartilage regeneration.
Geographical variability and cultural diversity of reindeer pastoralism in northern Russia: delimitation of areas with different types of reindeer husbandry
Authors: Klokov Konstantin B. 
Published: June 2023

AbstractTraditional reindeer husbandry in Russia is a fascinating phenomenon of northern pastoralism and nomadism. Russia is home to over two-thirds of the world’s total domesticated reindeer herd. Reindeer husbandry in Russia is practised by 15 indigenous peoples, some of whom still pursue a nomadic lifestyle. The purpose of this article is to visualise reindeer husbandry, together with its hosting biophysical and social environment, as a socio-ecological system or a reindeer pastoralist landscape, and to present its diversity as a geographical system of landscape zones and regions. Such a holistic landscape approach is rooted in the landscape ecology and reflects the basic patterns of reindeer husbandry’s connections with its surroundings. The research includes 3 stages. We started by dividing the entire reindeer husbandry area of the Russian North into several landscape zones focusing on the predominant migration patterns of reindeer herders, as such patterns reflect the interaction of reindeer husbandry with the geographical environment as a whole. The next stage was zoning by cultural types of reindeer husbandry. In the final stage, we divided the particular reindeer husbandry areas into smaller regions according to the local features of reindeer pastoralism. The research has resulted in a map of traditional reindeer husbandry landscape zoning. This map embraces the whole territory of Russia where traditional reindeer husbandry still exists and comprises 35 units (reindeer pastoralist landscapes) related to four taxonomic levels. The present zoning scheme of Russian reindeer husbandry is, on the one hand, a result but, on the other hand, a tool for further research on reindeer pastoralism within a holistic landscape ecology approach.