bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of tumor-infiltrating lymphocytes (TILs) in molecular subtypes of an Indian cohort of breast cancer patients
Authors: Vaid Pooja M. , Puntambekar Anirudha K. , Jumle Nutan S. , Banale Rituja A. , Ansari Danish , Reddy Ruhi R. , Unde Rohini R. , Namewar Namrata P. , Kelkar Devaki A. , Shashidhara L. S. , Koppiker Chaitanyanand B. , Kulkarni Madhura D. 
Published: November 2022

Abstract
Objectives
Evaluation of tumor-infiltrating lymphocytes (TILs) distribution in an Indian cohort of breast cancer patients for its prognostic significance.

Methods
A retrospective cohort of breast cancer patients from a single onco-surgeon’s breast cancer clinic with a uniform treatment strategy was evaluated for TILs. Tumor sections were H&E stained and scored for the spatial distribution and percent stromal TILs infiltration by a certified pathologist. The scores were analysed for association with treatment response and survival outcomes across molecular subtypes.

Results
Total 229 breast cancer tumors were evaluated. Within spatial distribution categories, intra-tumoral TILs were observed to be associated with complete pathological response and lower recurrence frequency for the entire cohort. Subtype-wise analysis of stromal TILs (sTILs) re-enforced significantly higher infiltration in TNBC compared to HER2-positive and ER-positive tumors. A favourable association of higher stromal infiltration was observed with treatment response and disease outcomes, specifically in TNBC.

Conclusion
Intra-tumoral TILs showed a higher proportion with favourable association with better patient outcomes in an Indian cohort, unlike western cohorts where both stromal and intra-tumoral TILs show similar association with prognosis. With further validation, TILs can be developed as a cost-effective surrogate marker for treatment response, especially in a low-resource setting such as India.
Treatment barriers among young adults living with a substance use disorder in Tshwane, South Africa
Authors: Nyashanu Tichaenzana , Visser Maretha 
Published: November 2022

Abstract
Background
Despite increasing substance use globally, substance use treatment utilisation remains low. This study sought to explore and measure substance use treatment barriers among young adults in South Africa.

Methods
The study was done in collaboration with the Community-Oriented Substance Use Programme run in Tshwane, South Africa. A mixed methods approach employing focus group discussions with key informants (n = 15), a survey with a random sample of people using substances and receiving treatment (n = 206), and individual semi-structured interviews (n = 15) was used. Descriptive statistics and thematic analysis were used to analyse data.

Results
Contextual barriers seemed more prominent than attitudinal barriers in the South African context. Fragmented services, stigma-related factors, an information gap and lack of resources and support (contextual factors), perceived lack of treatment efficacy, privacy concerns, and denial and unreadiness to give up (attitudinal factors) were treatment barriers that emerged as themes in both quantitative and qualitative data. Culture and religion/spirituality emerged as an important barrier/facilitator theme in the qualitative data.

Conclusion
Interventions need to embrace contextual factors such as culture, and more resources should be channelled towards substance use treatment. Multi-level stakeholder engagement is needed to minimise stigmatising behaviours from the community and to raise awareness of available treatment services. There is a need for strategies to integrate cultural factors, such as religion/spirituality and traditional healing, into treatment processes so that they complementarily work together with pharmacological treatments to improve health outcomes.
Chemoradiation versus surgery for superficial esophageal squamous cell carcinoma after noncurative endoscopic submucosal dissection: comparison of long-term oncologic outcomes
Authors: Suzuki Gen , Yamazaki Hideya , Aibe Norihiro , Masui Koji , Kimoto Takuya , Nagasawa Shinsuke , Watanabe Shou , Seri Shou , Asato Akito , Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Dohi Osamu , Ishikawa Takeshi , Elsaleh Hany , Yamada Kei 
Published: November 2022

Abstract
Background
Esophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD.

Methods
This study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC.

Results
Data were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups.

Conclusions
CRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.
Clinical and radiological outcome of Mason-Johnston types III and IV radial head fractures treated by an on-table reconstruction
Authors: Kastenberger Tobias , Kaiser Peter , Spicher Anna , Stock Kerstin , Benedikt Stefan , Schmidle Gernot , Arora Rohit 
Published: November 2022

Abstract
Background
Only few methods treating comminuted radial head fractures have been established providing sufficient joint reconstruction, restoring radial length and enabling early joint mobilization. When an anatomical reconstruction using open reduction and internal fixation is not possible, radial head resection or primary arthroplasty is often conducted. An “Ex situ/on-table” reconstruction is widely disregarded but can be an option. The purpose of this study was to evaluate the functional and radiological outcome of comminuted radial head fractures treated with an “on-table” reconstruction and internal fixation using a low profile plate.

Methods
Fourteen patients who sustained a radial head fracture (9 Mason-Johnston type III and 5 Mason-Johnston type IV) and were treated with an “on-table” reconstruction between 2010 and 2020 were evaluated retrospectively. The patients mean age was 41.3 years (range 21–69). The clinical evaluation included active range of motion, grip strength, pain level and elbow stability. The functional outcome was assessed using the Disability of Arm, Shoulder and the Hand (DASH) score, Mayo Elbow Performance Index (MEPI), Broberg and Morrey score. The radiological examination included a.p. and lateral views of the injured elbow to evaluate nonunions, loss of reduction, joint alignment, avascular radial head necrosis, heterotopic ossifications and posttraumatic osteoarthritis.

Results
The inclusion rate was 74% with a mean follow-up of 50 months (range 16–128). The mean elbow flexion of the injured side was 126° (range110–145°) with an average extension loss of 8° (range 0–40°). Pronation was 65° (15–90°) and supination 66° (5–90°). The mean MEPI was 87 points (range 45–100). The mean DASH score was 13 points (range 1–88). According to the Broberg and Morrey functional scoring system, the average score was 92 points (range 88–100). Complete bone union was achieved in 9 cases, partial union in 4 cases and nonunion in one case. There were no signs of avascular necrosis of the radial head. Signs of post-traumatic osteoarthritis were seen in 11 cases. Five patients needed an implant removal due to a radio-ulnar impingement and one patient a revision surgery due to the nonunion and implant breakage.

Conclusions
An on-table (ex situ) reconstruction of the radial head is a reliable option with a good clinical outcome and low complication rate in the surgical treatment of comminuted radial head fractures. It can restore joint alignment and maintain radial length. The risk for avascular necrosis is neglectable, and the bone healing rate is high.
The efficacy and safety of platelet-rich plasma in the tendon-exposed wounds: a preliminary study
Authors: Deng Zhuan , Long Zhi-Sheng , Gong Fei-Peng , Chen Gang 
Published: November 2022

Abstract
Objective
Currently, among wounds with large skin tissue defects caused by various reasons, the treatment of refractory wounds is still a major clinical problem. This study is aimed to preliminarily assess the therapeutic potentials of platelet-rich plasma (PRP) in refractory wounds with exposed tendons, as well as corresponding efficacy and safety.

Methods
A total of 12 patients (5 males and 7 females) with refractory wounds and exposed tendons who were admitted to our hospital from June 2018 to December 2020 were included in this study. After the preparation of PRP, the included patients underwent the PRP injection after the debridement of wounds, and the efficacy and prognosis were assessed by the same group of senior surgeons.

Results
The average age of included patients was 42.7 ± 12.9 years, and the causes of injury included traffic accidents (3 cases), contusion (2 cases), burns (2 cases), diabetes complications (4 cases), and melanoma complications (1 cases). The average healing time was 23.0 ± 5.0 days, and the mean size of the wound was 3.1 × 5.1 cm2. During the whole treatment process, Vancouver Scar Scale (VSS) decreased from 7.4 ± 1.6 before PRP treatment to 3.6 ± 0.9 after treatment (P < 0.001), Manchester Scar Scale (MSS) decreased from 12.3 ± 4.5 before PRP treatment to 5.4 ± 1.2 after treatment (P < 0.001), and no redness and swelling were observed around wounds, the size and degree of wounds gradually reduced, the coverage rate of granulation tissue was acceptable, overall quality of scar was relatively good, skin sensitivity around wounds was normal, there was no local wounds secretion, and postoperative patient's satisfaction was relatively good during follow-up.

Conclusions
Our study has preliminarily indicated that PRP can promote the wounds healing, reduce the inflammation around wounds, and improve the granulation tissue and angiogenesis, thereby effectively polishing up the safety and efficacy.
Mitral annuloplasty with the interatrial groove-left atrial dome approach in a patient with Marfan syndrome
Authors: Chen Fengjie , Wang Xiang , Zhuang Xianmian , Guo Hongwei 
Published: November 2022

Abstract
Background
The choice of mitral valve surgical approach has always been a difficult problem in patients with small left atrium.

Case presentation
We report a case of a patient with Marfan syndrome who underwent the David operation and mitral annuloplasty. The patient had a small left atrium, so we severed the superior vena cava and opened the interatrial groove and left atrial dome. This method allows for excellent exposure of the mitral valve and subvalvular apparatus, enabling a successful operation.

Conclusion
The interatrial groove-left atrial dome approach provides an option for patients with a small left atrium undergoing mitral valve surgery.
Integrated dose–response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine
Authors: Chen Yan-Yan , Chen Jia-Qian , Tang Yu-Ping , Shang Er-Xin , Zhao Qi , Zou Jun-Bo , Xu Ding-Qiao , Yue Shi-Jun , Yang Jie , Fu Rui-Jia , Zhou Gui-Sheng , Duan Jin-Ao 
Published: November 2022

Abstract
Background
Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose–response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment.

Methods
The proposed methodology of integrated dose–response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose–response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM.

Results
This developed strategy was successfully applied to rhubarb. The dose–response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case.

Conclusion
An integrated dose–response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.
“Older people tend to be invisible”: a qualitative study exploring the needs and inclusion of older Syrian refugees in the context of compounding crises in host country, Lebanon
Authors: Hachem Sarah , Ali Souad , Al-Omari Sarah , Abi Chahine Maya , Fahme Sasha Abdallah , Mehio Sibai Abla 
Published: November 2022

Abstract
Background
Older Syrian refugees in Lebanon are a marginalized population with under-recognized health needs. The inclusivity of this population within the humanitarian response is poorly understood. This study aims to identify the unique needs of older Syrian refugees in the context of recent concurrent crises in Lebanon, and explore the extent to which they are being met and prioritized by local and international aid agencies.

Methods
We conducted in-depth interviews with a snowball sample of 26 stakeholders from 11 organizations operating in the health, nutrition, and water, sanitation, and hygiene sectors. Data analysis followed principles of thematic analysis.

Results
Concurrent political, economic, and public health crises in host country promoted income insecurity among older refugees and increased dependency on younger relatives, leading to food insecurity, neglect, and poor health outcomes, including the sequelae of untreated non-communicable diseases. Mental illness was perceived to be exacerbated by Covid-19 related challenges, including social isolation, uncertainty about the future, and additionally due to feelings of guilt related to economic dependence and fundamental exclusion from labor force participation. Despite their vulnerability, older refugees are overlooked by the humanitarian response, which may be related to a lack of data. Pervasive medication shortages in the setting of the economic collapse, as well as inaccessible physical environments and competing interests were all identified as major barriers to care.

Conclusions
Older Syrian refugees in Lebanon experience dual vulnerability that is acutely exacerbated in the setting of concurrent crises. Sociopolitical, economic, and cultural barriers promote social exclusion and may confer an increased risk of income and food insecurity in this population, with significant implications for health. Humanitarian aid agencies operating in the context of fragmented, under-resourced health systems are currently unable to sufficiently address multi-faceted needs of this community. We recommend moving away from a donor-dependent model of aid by allocating resources toward strengthening inclusive national health systems that emphasize preventative care. We further call for age-disaggregation of routine data and normalization of data sharing among stakeholders in the academic and public health sectors in order to develop evidence-based initiatives that can meet the needs of this under-served community.
The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis
Authors: Parantainen J. , Barreto G. , Koivuniemi R. , Kautiainen H. , Nordström D. , Moilanen E. , Hämäläinen M. , Leirisalo-Repo M. , Nurmi K. , Eklund K. K. 
Published: November 2022

Abstract
Background
Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients.

Methods
We measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays.

Results
The patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation.

Conclusion
We describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor.

Graphical Abstract
A graphical summary of the conclusions of the study.
Optic nerve sheath diameter at high altitude: standardized measures in healthy volunteers
Authors: Rodríguez Aparicio Edith Elianna , Carrizosa Gonzalez Jorge Armando , Rodriguez Lima David Rene 
Published: November 2022

Abstract
Background
Increases in the diameter of the optic nerve sheath (ONSD) on ultrasound are associated with high intracranial pressure (hICP). The normal value varies with altitude and the population studied. The objective of this study is to describe the normal values of the ONSD in a healthy adult population of the city of Bogotá, Colombia, at 2640 meters above sea level (masl).

Patients and methods
A prospective observational study was conducted on a total of 247 healthy individuals recruited from May 2021 to May 2022 who were subjected to the color, low power, optic disk, safety, elevated frequency, dual (CLOSED) protocol for measuring the bilateral ONSD adjusted to the eyeball transverse diameter (ETD).

Results
A total of 230 individuals were analyzed; the average ONSD of the right eye (RE) was 0.449 cm (range 0.288–0.7) and that of the left eye (LE) was 0.454 cm (range 0.285–0.698); the correlation between RE and LE was 0.93 (p < 0.005), and the correlation of the ONSD/ETD ratios for the RE and LE was lower (r2 = 0.79, p < 0.005). A total of 10.8% of the studied population had values greater than 0.55 cm.

Conclusions
The median ONSD and ONSD/ETD ratio in the city of Bogotá are similar to those described in other populations; however, approximately 10.8% of the healthy population may present higher values, which would limit the use of ONSD on its own for clinical decision-making, only repeated measurements with significant changes in the ONSD and ONSD/ETD or asymmetries between the measurements of both eyes linked to clinical findings would allow the diagnosis of hICP.
Biomimetic synthesis of iron oxide nanoparticles from Bacillus megaterium to be used in hyperthermia therapy
Authors: Hajiali Sajedeh , Daneshjou Sara , Daneshjoo Somayeh 
Published: November 2022

AbstractThe suitable structural characteristics of magnetic nanoparticles have resulted in their widespread use in magnetic hyperthermia therapy. Moreover, they are considered a proper and operational choice for pharmaceutical nanocarriers. Using the biomimetic method, we were able to produce iron oxide magnetic nanoparticles from the bacterial source of PTCC1250, Bacillus megaterium, for therangostic diagnosis systems and targeted drug delivery. Some of the benefits of this method include mitigated environmental and biological dangers, low toxicity, high biocompatibility, cheap and short-term mass production possibilities in each synthesis round compared to other biological sources, simple equipment required for the synthesis; and the possibility of industrial-scale production. Bacillus megaterium is a magnetotactic bacteria (MTB) that has a magnetosome organelle capable of orienting based on external magnetic fields, caused by the mineralization of magnetic nanocrystals. Utilizing this capability and adding an iron nitrate solution to the bacterial suspension, we synthesized iron oxide nanoparticles. The extent of synthesis was measured using UV–visible spectrophotometry. The morphology was evaluated using FESEM. The crystallized structure was characterized using RAMAN and XRD. The size and distribution of the nanoparticles were assessed using DLS. The surface charge of the nanoparticles was measured using zeta potential. The synthesis of iron oxide nanoparticles was confirmed using FT-IR, and the magnetic property was measured using VSM. This study is continued to identify industrial and clinical applications.
Identifying common core outcome domains from core outcome sets of musculoskeletal conditions: protocol for a systematic review
Authors: Sabet Tamer S. , Anderson David B. , Stubbs Peter W. , Buchbinder Rachelle , Terwee Caroline B. , Chiarotto Alessandro , Gagnier Joel , Verhagen Arianne P. 
Published: November 2022

Abstract
Background
Core outcome sets (COSs) aim to reduce outcome heterogeneity in clinical practice and research by suggesting a minimum number of agreed-upon outcomes in clinical trials. Most COSs in the musculoskeletal field are developed for specific conditions. We propose that there are likely to be common core domains within existing musculoskeletal COSs that may be used as a starting point in the development of future COSs. We aim to identify common core domains from existing COSs and to facilitate the development of new COSs for musculoskeletal conditions. As a secondary aim, we will assess the development quality of these COSs.

Methods
A systematic review including musculoskeletal COSs. We will search Core Outcome Measures in Effectiveness Trials (COMET) database, MEDLINE, EMBASE, Scopus, Cochrane Methodology Register and International Consortium for Health Outcome Measurement (ICHOM). Studies will be included if related to the development of a COS in adults with musculoskeletal conditions and for any type of intervention. Quality will be assessed using the Core Outcome Set-Standards for Development (COS-STAD) recommendations. Data extracted will include scope of the COS, health condition, interventions and outcome domains. Primary outcomes will be all core domains recommended within each COS. We define a common core outcome domain as one present in at least 67% of all COSs. All findings will be summarized and presented using descriptive statistics.

Discussion
This systematic review of COSs will describe the core domains recommended within each musculoskeletal COS. Common domains found may be used in the initial stages of development of future musculoskeletal COSs.

Systematic review registration
PROSPERO CRD42021239141